After a challenging year in which Regeneron has seen its per-share stock price tumble from a high in January of this year to a low of less than $14 per share less than six months later (June of 2008), industry analysts are becoming increasingly bullish on the future of the Tarrytown, New York—based biotechnology company.

The company—which emphasizes in-house drug development and employs more than 700 people (In addition to the Company’s corporate headquarters, Regeneron has a large-scale biologics manufacturing facility in Rensselaer, New York, where it produces commercial and investigational products for its clinical trials)&mdash; saw its stock market fortunes take a hit in May 2008 when a promising cancer drug candidate, aflibercept, yielded disappointing phase III data in an ovarian cancer population that failed to live up to investor expectations. The downturn was likely exacerbated by the broader market decline, which has been taking place of late.

Now that the dust has settled from the phase III trial disappointment, however, many are taking a fresh look at the company and wondering if the second quarter 2008 sell-off of Regeneron was not an overreaction. The potential strength of product candidates currently in development is significant and seems to be fueling a general reassessment of the company that is increasingly optimistic. Also, the company has some fiscal room to breathe and maneuver as it moves its drug through the development pipeline. According to a company spokesperson, Regeneron’s cash position is relatively strong and will be enough to last until the company attains profitability. The company is expected to post a profit in 2010. Currently, the stock has posted a mini-rally and has been hovering between $17 and $18 per share.

Aflibercept, despite its recent phase III ovarian cancer setback, continues to be studied in other cancers (i.e., brain cancer) and a future ovarian cancer indication, although delayed, may be attained eventually. Indeed, in a recent phase II trial evaluating the agent in relapsed and difficult-totreat brain tumors, response rates of 50% and 30% were achieved in patients with anaplastic glioma and glioblastoma, respectively. As Leonard Schleifer, MD, PhD chief executive officer, Regeneron, recently commented, “We’re moving ahead progressively (with aflibercept), and the big picture is still a significant competitor to Genentech’s Avastin.”

In addition to presenting a variety of promising data at the recent American Society of Clinical Oncology annual meeting (most notably two studies evaluating a potential metastatic colorectal cancer product and one study on a potential glioblastoma candidate), the company has further fueled investor optimism with the announcement of major partnerships with Sanofi-Aventis and Bayer Healthcare. The deal with Sanofi is to jointly develop and commercialize fully-human therapeutic antibodies utilizing Regeneron’s proprietary VelociSuite technology and the agreement with Bayer is designed to facilitate the global development of eye disease therapies based on Regeneron’s proprietary Trap technology. The Trap technology is expected to yield products in oncology and a number of other sectors. Also, such proprietary technologies and platforms make the company an attractive partner for potentially lucrative intercompany collaborations. The company has also developed a VelcoImmune technology that analysts expect will attract additional partners over the next few years.

According to the company website, “the company’s ability to develop product candidates is enhanced by the application of several proprietary technologies that Regeneron has incorpo- rated into a comprehensive drug discovery and development process. This process is designed to thoroughly understand the biology of specific diseases, discover potential therapeutic candidates, and evaluate these candidates in clinical trials.” In other positive news for the company, the FDA recently approved the company’s Arcalyst (rilonacept) for CIAS1-associated periodic syndrome, a rare genetic disorder.

The general consensus of industry watchers is that Regeneron’s future success or failure will be based on the performance of its research pipeline. Currently, Regeneron has therapeutic candidates in clinical trials for the potential treatment of cancer (Figure), eye diseases, and inflammatory diseases. Regeneron has four clinical development programs: (1) aflibercept in cancer, in collaboration with Sanofi-Aventis, and (2) the VEGF Trap-Eye, in collaboration with Bayer HealthCare, (3) rilonacept (IL-1 Trap), where the company is currently evaluating the potential role of rilonacept in other conditions in which Interleukin-1 (IL-1) may play a role, and REGN88, an antibody to the Interleukin-6 receptor (IL-6R).

Regeneron also has a number of solid pre-clinical drug candidates for a variety of disorders. The collaboration with Sanofi alone plans to introduce two to three new antibody candidates into clinical development each year going forward. Much of the preclinical company research into oncology has yet to yield dividends in terms of named agents.

However, the company, owing to its proprietary technologies and platforms (which have been utilized to identify specific cancer gene targets and better understand the processes of malignancy) has made significant progress toward this end. A Regeneron spokesperson explained, “the development of novel strategies to selectively target the tumor blood supply is bolstering traditional antitumor therapies. The growth of solid tumors requires the development of new blood vessels, or angiogenesis, to sustain the cancer by providing oxygen and nutrients. Regeneron has been a pioneer in discovering vascular specific targets such as angiopoietins. Regeneron is leveraging its discovery platforms, such as microarray and VelociGene, to identify genes that are over-expressed in tumors that could be targets for therapeutic intervention. Multidisciplinary scientists in the oncology, microarray, and VelociGene groups have worked together to identify the next generation of antiangiogenesis and antitumor targets.”

Denosumab Demonstrates Efficacy in Prostate Cancer Population

Amgen announced that the first pivotal study to evaluate its bone drug denosumab in men with nonmetastatic prostate cancer has met its endpoints.

The three-year, phase III HALT study, conducted on men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer, enrolled 1,400 patients. Findings indicated that Amgen’s drug affected statistically significantly greater increases in bone mineral density at the lumbar spine and nonvertebral sites compared with the placebo at multiple time points—consistent with prior denosumab studies.

Men treated with denosumab also experienced less than half the incidence of new vertebral fractures compared with those receiving placebo, which was the secondary endpoint. There were also fewer nonvertebral fractures over the 36-month period. In fact, the drug demonstrated a clearly defined trend (albeit not statistically significant) in reduction of nonvertebral fracture over the 36-month follow-up period. The company said the incidence and type of adverse events were similar between the arms of the study. Serious adverse infections occurred in 5% of the placebo-receiving population and 6% of those in the denosumab arm.

According to an Amgen spokesperson, these data show that denosumab makes the spine stronger in patients whose bones thin out because they are taking hormone depriving drugs to combat their prostate cancer.

In the interests of clarity, it is relevant to note that the denosumab study results reported herein are separate from the denosumab data expected later this quarter on women with postmenopausal osteoporosis, the results of which are highly anticipated by Amgen stakeholders and industry watchers.

The fracture reduction data bodes well for the outcomes of the anxiously awaited osteoporosis study (known as the D-mab FREEDOM study), which has fracture reduction as its primary endpoint.

Amgen plans to publish the data in a major medical journal and present the data at an upcoming medical conference. Sector analysts point out that it remains to be seen if denosumab can show a better potency relative to generic alendronate (the current standard of care) in the osteoporosis setting.

In related Amgen news, the company announced that it will pay Johnson & Johnson $200 million to settle litigation alleging drug discounts offered by Amgen to cancer clinics violated antitrust laws. Johnson & Johnson’s Ortho Biotech unit had argued in a 2005 lawsuit that Amgen was bundling sales of its infectionfighting and anti-anemia drugs in a way that forced cancer clinics to buy Amgen’s Aranesp rather than Johnson & Johnson’s competing drug Procrit.

Aranesp is a longer-lasting version of Amgen’s anemia drug Epogen, which is marketed for treatment of patients with kidney disease. Johnson & Johnson holds a license for sales of the older drug (under the brand name Procrit) as a treatment for patients with cancer undergoing chemotherapy. Amgen said in a statement its conduct was not unlawful and it admits to no wrongdoing. Amgen also sells two other drugs, Neulasta and Neupogen, that increase production of infection-fighting white blood cells and are also used in chemotherapy patients.

Eli Lilly and Company and SGX Pharmaceuticals, Inc., have signed a definitive merger agreement providing for the former’s acquisition of the latter in an all-cash transaction. SGX, based in San Diego, is a biotechnology company focused on drug discovery and development in the area of oncology. Under the terms of the agreement, Lilly will acquire all of the outstanding shares of SGX common stock at a price of $3.00 per share, for a total purchase price of approximately $64.0 million.

According to industry watchers, the acquisition provides yet another example of a broader industry trend of consolidation in which large traditional pharma companies buttress their presence in specific sectors (i.e., oncology) through the purchase of smaller but up and coming biotechnology companies. (Many of these transactions have been covered in recent issues of Oncology & Biotech News.) This strategy allows major drug companies to leverage their purchasing power in order to become instant players in sectors that may have taken them years to compete in had they attempted to pursue in-house development strategies. The Lilly-SGX deal, for example, will allow Lilly to integrate SGX’s drug discovery platform into its drug discovery efforts and to develop and bring to market an impressive portfolio of preclinical oncology compounds focused on a number of high-value kinase targets.

Since entering into a collaboration in 2003, Lilly has partnered with SGX to determine 3-dimensional structures of key Lilly drug targets utilizing SGX’s proprietary X-ray crystallography technology. The ongoing collaboration also provided Lilly with access to the SGX synchrotron beamline facility, SGX-CAT, which is a state-of-the-art synchrotron facility enabling X-ray crystallography and protein structure determination built by SGX at the Advanced Photon Source (APS) located at the Department of Energy’s Argonne National Laboratory in Chicago.

“After a successful collaboration over the past several years, we are excited to bring the scientific and technological expertise of SGX into Lilly’s research organization, while at the same time expanding our presence in the San Diego area,” commented Steven M. Paul, MD, executive vice president, science and technology, Eli Lilly, “We will leverage the combined resources of both companies to strengthen our structural biology capabilities and seek out innovative therapies for patients.”

“We believe that this merger provides an excellent opportunity for the potential of SGX’s platform and pipeline to be realized, while simultaneously providing our shareholders with attractive financial terms,” stated Mike Grey, chief executive officer, SGX Pharmaceuticals, “As we have evolved from a platform technology organization to a drug discovery company, we believe that this transaction represents a timely opportunity to place our programs and technology assets in the hands of a world-class company with the experience and resources to advance innovative treatments for patients.”

The board of directors of SGX voted unanimously to approve the merger agreement and to recommend that its shareholders approve the transaction. The transaction is expected to close in the second half of 2008. Closing is contingent upon approval by SGX shareholders, clearance under the Hart-Scott-Rodino Antitrust Improvements Act and certain other closing conditions. Upon the closing of the transaction, Lilly will incur a onetime charge to earnings for acquired in-process research and development, but it is premature to estimate what that charge will be.

In related news, SGX Pharmaceuticals announced that it has submitted an investigational new drug application to the FDA for SGX393. The compound is designed to treat relapsed and refractory chronic myelogenous leukemia.

Hana Biosciences Presents Positive Data on Two Promising Oncology Candidates

At the recent European Society for Medical Oncology Conference in Lugano, Switzerland, Hana Biosciences, South San Francisco, presented data on Alocrest (vinorelbine liposomes injection, Optisome) and menadione topical lotion, two of the company’s potential oncology products.

Alocrest is currently in development for the treatment of certain solid tumor cancers and lymphomas. Menadione is being evaluated for the possible treatment and/or prevention of epidermal growth factor receptor inhibitor (EGFRI)— associated skin toxicities.

Hana presented data from the company’s phase I clinical trial of Alocrest. A total of 30 subjects with advanced solid tumors or non-Hodgkin’s lymphoma (NHL) were enrolled in the phase I trial. The majority of the patients were classified as heavily pretreated. Overall, this study achieved a disease control rate of 47%, including three of four elderly non— small cell lung cancer (NSCLC) subjects who achieved stable disease. Of 27 subjects with refractory solid tumors and three subjects with NHL evaluable for efficacy, one patient achieved a partial response (PR) (unconfirmed) and 13 patients achieved stable disease (SD). A maximum tolerated dose (MTD) of 28 mg/m2 administered via a 60-minute IV infusion on days 1 and 8 every 21 days was established in this population.

While a separate MTD was not determined for non-heavily pretreated subjects, Hana believes that the dose level could potentially be safely increased in patients who have received fewer rounds of prior treatment with other chemotherapy agents. Alocrest was generally well tolerated with reversible neutropenia as the most common dose-limiting toxicity. Optisomal encapsulation imparted no new toxicities and none of the patients experienced an injection site reaction. The phase I study was conducted at the Cancer Therapy and Research Center and the START facility in San Antonio and McGill University in Montreal.

“We are pleased to report phase I data for Alocrest demonstrating prolonged stable disease and a solid tolerability profile at an MTD comparable to unencapsulated vinorelbine in heavily pretreated patients,” said Anne Hagey, MD, vice president and chief medical officer, Hana Biosciences, “Based on these data, we continue to believe Alocrest has the potential to provide improved efficacy compared to conventional vinorelbine. Alocrest may be particularly beneficial to patient populations who cannot tolerate treatment with standard multi-agent chemotherapy regimens, such as elderly patients with NSCLC.”

In a separate session at the same meeting, researchers presented results of preclinical studies of menadione that were conducted to better understand the potential interaction between topical menadione and systemically delivered erlotinib (Tarceva), an approved EGFRI. Analysis from tests conducted in an in vivo model demonstrated that topical menadione did not affect the antitumor effect of erlotinib. 

 studies were also conducted to investigate menadione’s ability to restore kinase activity in the presence of specific kinase inhibitors. These data indicate that treatment with menadione may result in restoration of normal cell turnover rates and prevent skin toxicities that result from inhibition of protein kinases associated with tumor growth signaling pathways, such as the tyrosine kinases MEK, CDK and RAF.

“Results presented from preclinical studies of menadione topical lotion demonstrate that this compound does not interfere with the anticancer activity of Tarceva, an EGFRI, in a sensitive model. These data are encouraging and help provide the foundation of our strategy to develop this agent for the prevention and treatment of the skin toxicities associated with use of EGFRIs,” stated Dr. Hagey. “In addition, the initial data suggesting that menadione may also be useful in preventing and/or treating skin toxicities associated with the growing class of kinase inhibitors extends the exciting potential for this promising novel agent.”

Cephalon Drug Elicits Marked Response in Non-Hodgkin’s Lymphoma Population

Cephalon Inc. announced that its leukemia drug Treanda (bendamustine hydrochloride), when utilized in combination with Genentech Inc.’s Rituxan (rituximab), prompted a response in non-Hodgkin’s lymphoma (NHL) patients during a midstage study.

In the multicenter, open-label, single arm, phase II study, 66 patients with relapsed, indolent B-cell or mantle cell lymphoma without documented resistance to prior rituximab therapy were treated. Overall response rate was 92% with a complete response (CR) rate of 41%. A CR was defined as being achieved when after treatment with the Treanda and rituximab combination, patients had no detectable evidence of disease. Observed responses were durable, with a median duration of 21 months overall (19 months for the mantle cell population). Additionally, the combination of Treanda and rituximab was associated with progression- free survival of 23 months overall and for patients with mantle cell lymphoma.

As per the design of the study regarding dosing, patients received rituximab 375 mg/m2 intravenously on day 1and Treanda 90 mg/m2 intravenously on days 2 and 3 of a 28-day cycle for up to six cycles. An additional dose of rituximab was given one week before the first cycle and four weeks after the last cycle.

According to researchers, the combination of the two agents was generally well tolerated.

The study results were published in the most recent issue of the 

 and were part of a series of study data filed with the FDA over the past several months. Cephalon is in the process of seeking FDA approval for an expanded indication of Treanda. If the company is successful in its efforts, Treanda utilization will be expanded to encompass non-Hodgkin’s lymphoma. The drug, as of March 2008, was approved by the FDA for the treatment of chronic lymphocytic leukemia. The company expects an FDA decision on the use of Treanda in NHL by October 31st of this year.

Commenting on the significance of the newly published research, Charles Morris, MD, vice president, worldwide clinical research, Cephalon, stated, “A variety of treatment options have been employed in patients with indolent B-cell and mantle cell lymphomas, but resistance to treatment in this patient population often limits effective therapeutic options. Based on what we saw in this study, the combination of Treanda with rituximab appears to elicit a high rate of durable responses and encouraging progressionfree survival.”

Over the past year, Cephalon stock has been volatile, largely because of investor speculation regarding the amount of revenue that will ultimately be realized by Treanda.

Peregrine Pharmaceuticals Reports Positive Early Results for Breast Cancer Agent

Peregrine Pharmaceuticals, Inc., Tustin, California, reported that its lead product candidate bavituximab achieved the prespecified stage 1 primary endpoint in its ongoing phase II clinical trial in patients with metastatic breast cancer. The trial is an openlabel, Simon two-stage design to evaluate the safety and efficacy of a combination of bavituximab and docetaxel in patients with metastatic breast cancer.

The primary objective of the multicenter phase II clinical trial was to assess overall tumor response rate. Secondary objectives included measuring time to tumor progression, duration of response, overall patient survival and safety parameters. All tumor responses in the trial are being evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients may continue to receive bavituximab as solo therapy after completion of chemotherapy as long as the cancer does not progress and side effects are acceptable. According to the RECIST criteria, patients are categorized as having stable disease (SD) if they have less than a 20% increase to a 30% reduction in the sum of the target lesions, and they are categorized as having a partial response (PR) if they experience greater than a 30% reduction in the sum of target lesions. In addition, to be assigned a status of SD or PR, patients cannot have the appearance of any new lesions.

Fourteen of the 15 patients enrolled in stage 1 were deemed evaluable for tumor response, with seven achieving partial tumor responses and seven having stable disease at week 8 according to RECIST criteria. All 14 of the evaluable patients remain in the study and are continuing to receive treatment, along with continuing assessments of tumor response. With the stage 1 primary endpoint of six or more objective tumor responses achieved, the design of the clinical trial now allows for an additional 31 study patients to be enrolled.

“We are very pleased with the early positive results from this phase II breast cancer study,” said Steven W. King, president and chief executive officer, Peregrine, “We are particularly encouraged by the fact that at an early time point of eight weeks, half of the patients had achieved objective tumor responses. Equally encouraging is that with patients now out over four months since the start of the study, none have shown tumor growth or disease progression. As these patients continue on treatment, we will continue assessing them for signs of antitumor activity. We look forward to sharing more data from this study as patient treatment and follow- up progress.”

Bavituximab, a novel monoclonal antibody, is currently in two phase II combination therapy trials for the treatment of metastatic breast cancer and for the treatment of non—small cell lung cancer (NSCLC). In addition, a phase I bavituximab monotherapy trial in advanced solid cancers is ongoing. Data presented at the 2008 ASCO annual meeting showed that half of evaluable patients in a phase Ib trial of bavituximab plus chemotherapy achieved an objective tumor response or stable disease after eight weeks of dosing, that the safety profile of bavituximab and chemotherapy appeared consistent with chemotherapy alone and that the pharmacokinetic properties of bavituximab were not affected by co-administration with conventional chemotherapies. A second phase II combination therapy study in patients with breast cancer is expected to begin soon.

According to the World Health Organization, breast cancer is the most commonly diagnosed cancer in women, and is second only to lung cancer as a leading cause of female cancer deaths.

Robust Lung and Breast Data Reported by Cell Therapeutics Oncology Candidate

Seattle-based Cell Therapeutics, Inc., published results from a randomized phase III trial comparing Opaxio (paclitaxel poliglumex, CT-2103) with gemcitabine or vinorelbine for the treatment of patients with previously untreated non—small cell lung cancer (NSCLC) in the most recent issue of the 

. Results showed that overall survival was similar between the Opaxio and gemcitabine or vinorelbine arms. Patients treated with Opaxio required less supportive care including fewer red blood cell transfusions, hematopoietic growth factors, and opioid analgesics than those patients receiving either gemcitabine or vinorelbine. Additionally, patients receiving Opaxio required fewer clinic visits because of its administration schedule, (once every 3 wk), and short infusion time, compared with patients receiving either gemcitabine or vinorelbine.

The objective of the study, known as STELLAR 4, was to determine if Opaxio would improve overall survival when compared with the standard singleagent treatments of gemcitabine or vinorelbine in patients with advanced NSCLC who had not previously received chemotherapy. The multicenter trial was conducted at 83 centers in 10 countries.

A total of 190 patients with advanced NSCLC were randomized to the comparator arm (half of whom received gemcitabine, the other half of whom received vinorelbine) 191 were randomized to the Opaxio arm.

Survival, time to progression (TTP), and response rates were similar in both arms. Median overall survival was 7.3 months in the Opaxio arm and 6.6 months in the control arm. The estimated one-year survival rate was the same in both arms (26%), and the approximate two-year survival rate was numerically higher in the Opaxio arm (15%) than the comparator arm (10%). Opaxio patients experienced a statistically significant decease in adverse events when compared with the control arm. In addition, fewer Opaxio patients (12%) discontinued treatment as a result of adverse events, compared with 17% of patients in the control arm.

In a separate phase II trial presented at the 2008 Annual Meeting of the American Society of Clinical Oncology, researchers evaluated the efficacy and tolerability of Opaxio in combination with capecitabine in first-line treatment of patients with metastatic breast cancer (MBC). Results indicated that 20 patients (42%) of the 48 evaluable patients demonstrated a confirmed tumor response, including two complete responses and 18 partial responses. Median duration of response was estimated to be 9.9 months. Estimated six-month overall survival was 86% and estimated progression-free survival was 45%. Investigators concluded the combination of paclitaxel poliglumex and capecitabine was well tolerated and active in MBC.

“Given the goal of the study was to determine if Opaxio combined with capecitabine, an oral chemotherapy agent, as first-line therapy in metastatic breast cancer would prove to be an active and relatively well tolerated regimen, the combination of Opaxio and capecitabine had efficacy similar to other taxane/capecitabine combinations and was well tolerated and active in this patient population,” commented Jack W. Singer, MD, chief medical officer, Cell Therapeutics. He also touted the agent’s “convenient dosing schedule…(lack of) requirement for premedications and minimal hair loss…compared to other taxanes.”

Articles

Physician's Financial News: May 28, 2010

The Clinical Benefit of Bevacizumab in Metastatic Colorectal Cancer

The utility of vascular endothelial growth factor (VEGF) inhibitors in colorectal cancer may be affected by mutations of the KRAS gene; patients with metastatic colorectal cancer who have the KRAS mutation have been found to not gain benefit anticipated with use of endothelial growth factor inhibitors. Researchers from Duke University, Durham, North Carolina, and Genentech, South San Francisco, California, sought to determine if the outcome of patients treated with bevacizumab, a VEGF inhibitor, is affected by KRAS mutation status.

The researchers analyzed the results of a phase III, placebo-controlled study of 812 patients with metastatic colorectal cancer that tested the efficacy of a regimen of fluorouracil, irinotecan, and leucovorin. Patients in the study group also received bevacizumab, whereas patients in the control group also received a placebo. Samples from the tumors of 230 patients were evaluable for KRAS status.

In patients with mutated KRAS genotypes, median progression-free survival was 9.3 months in those receiving bevacizumab, compared with 5.5 months in those receiving the control regimen (P = .0008). In those with wild-type KRAS, study group had a mean progression-free survival of 13.5 months compared with the control group’s median of 7.4 months (,i>P < .0001). In terms of overall survival, the median survivals were 19.9 months and 13.6 months, respectively for those with mutant KRAS samples (

 = .26). For those with wild-type KRAS, the median overall survivals were 27.7 months and 17.6 months, respectively (

The researchers concluded that KRAS status did not affect the benefit of bevacizumab treatment, even though patients with KRAS mutations experienced less benefit overall from treatment (both study and control). This means that KRAS testing in patients is unwarranted in patients who are candidates for bevacizumab treatment.

Hurwitz HI, Yi J, Ince W, et al: The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: Analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Presented at the 2008 World Congress on Gastrointestinal Cancer, Zurich, Switzerland, July 1, 2008.

Once-Daily Dasatinib Associated with Better Efficacy and Tolerability in Chronic Myeloid Leukemia

In patients with chronic-phase chronic myelogenous leukemia (CML) whose treatment with imatinib did not produce the desired remission, dasatinib 70 mg twice daily has proven effective and is the approved dosage. However, this dose schedule is associated with toxicity, which is thought to be related to continuous inhibition of Bcr-Abl gene expression. Can less-frequent dosing result in similar efficacy but with fewer tolerability issues? A team of international researchers conducted a phase III trial to better understand if toxicity can be reduced with oncedaily administration and what might be the best once-daily dose.

In this open-label study, the investigators randomly assigned 670 patients with imatinib-resistant or intolerant chronic-phase CML to one of four dasatinib treatment groups: (1) 100 mg once daily, (2) 50 mg twice daily, (3) 140 mg once daily, or (4) 70 mg twice daily.

After a minimum follow-up of six months and a median treatment duration of eight months, the clinicians examined response rates for hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) parameters from the four groups. Similar time to and duration of cytogenetic response were noted, as well as progression-free survivals. Disease progression or death occurred in 8% to 11% of all patients.

Patients taking dasatinib 100 mg once daily, when compared with the approved 70 mg twice-daily course of therapy, had significantly lower rates of pleural effusion (all grades, 7% vs. 16%, respectively; 

 = .024) and grade 3 to 4 thrombocytopenia (22% vs. 37%, respectively; 

 = .004). Fewer patients needed dose interruption (51% vs. 68%, respectively), treatment discontinuation (16% vs. 23%, respectively) and dose reduction (30% vs. 55%, respectively).

The researchers concluded that dasatinib 100 mg once daily remains the efficacy of 70 mg twice daily, but with less toxicity. They believe that efficacy may be preserved and adverse events reduced by intermittent target inhibition with tyrosine kinase inhibitors.

Shah NP, Kantarjian HM, Kim DW, et al: Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia.

New Mechanism Shows Promise in Patients With Non-Small Cell Lung Cancer

A new testing program is just getting underway to test the viability of another class of agents that address blood vessel supply to tumors. This class is distinct from an angiogenesis inhibitor, which tries to prevent tumors from growing new blood vessels; instead, a tumor-vascular disrupting agent will destroy blood vessels already created by the tumor.

ASA404, a product that has already undergone small phase II studies, is the subject of two phase III trials called Antivascular Targeted Therapy: Researching ASA404 in Cancer Treatment (ATTRACT). The ATTRACT-1 study will include roughly 1,200 patients who will be randomized to receive ASA404 1,800 mg/m2 plus carboplatin and cisplatin chemotherapy or placebo plus the standard chemotherapy as first-line treatment for non—small cell lung cancer (NSCLC). ATTRACT-2 will comprise approximately 900 patients, who will also be randomized to receive ASA404 plus docetaxel or placebo plus docetaxel for the second-line treatment of NSCLC.

The promise of this agent was seen in phase II trials, which indicated a median overall survival advantage of more than 5 months for patients with squamous-cell NSCLC taking first-line ASA404 plus chemotherapy compared with those receiving chemotherapy. Median time to tumor progression was improved by four months. Patients with squamous-cell history obtained more survival and time-to-progression benefit with ASA404 than did patients with non—squamous-cell tumors.

McKeage J, Jameson MB, AS1404-201 Study Group Investigators: Comparison of safety and efficacy between squamous and non-squamous non—small cell lung cancer (NSCLC) patients in phase II studies of DMXAA (ASA404). Presented at the 2008 annual meeting of the American Society of Clinical Oncology, Chicago, May 30–June 3, 2008. ASA404 programme to expand with new pivotal trial in lung cancer (press release). July 17, 2008

ASA404 programme to expand with new pivotal trial in lung cancer (press release). July 17, 2008.

Erectile Dysfunction Response to Androgen Deprivation Therapy for Prostate Cancer

Erectile dysfunction (ED) may be a common consequence of prostate cancer treatment with androgen deprivation therapy (ADT). Libido and sexual function can be altered because of ADT-induced changes in serum testosterone. Researchers from the University of Tennessee Health Science Center, Memphis, sought to quantify the incidence of patient-reported ED as well as their response to treatment for ED through the use of a retrospective database analysis.

Data from patients at the University who received ADT between January 1989 to July 2005 for prostate cancer were reviewed for ED reporting, libido changes, and ED therapy initiation (surgical or medical). The researchers analyzed the charts of 395 patients (mean age, 71.7 yr; 59% African—American, 41% Caucasian/ other, at ADT initiation). Treatment for ED in these subjects included phosphodiesterase type-5 (PDE-5) inhibition monotherapy (72%), prostaglandin E1 analogues alone (11%), vacuum erection devices alone (7%), inflatable penile prosthesis (2%), or a combination of treatments (9%).

Erectile dysfunction was reported in 57 (14.4%) of the individuals during the mean follow-up period of 87.4 months. Of those men, 40 (70%) had new-onset ED and 17 (30%) experienced ED before ADT. Medical therapy response rates were 33% to 80% (depending on therapy used—44% who were treated with PDE-5 inhibitor monotherapy responded).

Interestingly, the researchers revealed that patients younger than 70 years of age (

 < .001) were more likely to report ED than their older counterparts. Furthermore, multivariate analysis revealed that patients who did not have diabetes (

 = .024) were more likely to report ED after ADT. Both of these results could relate to the fact that patients older than 70 years and those with diabetes are in general more likely to have ED at baseline and therefore would not report a change.

Variable degrees of ED have been observed in men who are given ADT for prostate cancer, the researchers admitted. They believe that the best chance for a positive ED outcome may be through the use of multimodal therapy.

DiBlassio CJ, Malcolm JB, Derweesh IH, et al: Patterns of sexual and erectile dysfunction and response to treatment in patients receiving androgen deprivation therapy for prostate cancer. 

Motesanib Shows Potential For Thyroid Cancer Treatment

Although the value of using vascular endothelial growth factor (VEGF) inhibitors to halt cancer spread has not generally met expectations, angiogenesis inhibitors may have a role in extending life in patients with advanced cancer and poor prognosis. Researchers from the University of Texas M.D. Anderson Cancer Center and colleagues in 10 countries found that thyroid cancer metastasis was slowed in some patients by treatment with the VEGF inhibitor motesanib diphosphate.

This open-label, single-group trial enrolled subjects with progressive, locally advanced or metastatic, differentiated thyroid cancer that proved resistant to radioiodine therapy. Fifty-seven of the 93 participants (61%) had papillary thyroid carcinoma. An independent radiographic review (with magnetic resonance imaging or computed tomography) determined whether patients met the primary endpoint of having an objective response. Treatment comprised motesanib 125 mg given orally once a day for 48 weeks or until the disease progressed or side effects became unacceptable.

Of the 93 initial enrollees, 32 (34%) completed the entire 48-week treatment period. The therapy was halted in 35 patients because of disease progression and in 12 patients because of adverse events related to the treatment. Nine individuals withdrew from the study for various reasons and five patients died. An objective partial response to motesanib diphosphate was attained by 13 patients (14%). Stable disease occurred in 62 patients (67%) and durable stable disease was maintained by 33 of those individuals (35%) for 24 weeks or more. Seven patients (8%) had progressive disease without any improvement or period of stability. No response information could be obtained for 11 patients (12%), because radiographic scans were incomplete or could not be interpreted.

A genetic evaluation of 25 patients by the researchers revealed that patients with the BRAF V600E mutation in their tumor tissue demonstrated better objective response rates, but the patient numbers were too low to yield significantly different figures.

The median duration to response, as estimated by Kaplan—Meier survival analysis, was 32 weeks. The median progression-free survival was estimated to be 40 weeks. Thyroglobulin analysis was performed on 75 subjects, and 81% demonstrated a decrease in serum thyroglobulin concentrations when compared with baseline levels.

Treatment-related adverse events occurred in 87 patients (94%) with the most common being diarrhea (59%), hypertension (56%), fatigue (46%), and weight loss (40%).

The clinicians stated that patients with progressive advanced or metastatic differentiated thyroid cancer can achieve a partial response with motesanib diphosphate treatment, even though only a small percentage of all patients with the disease survive for 10 years. They suggested more research to better define the role of the BRAF V600E gene mutation as a marker of increased probability for success.

Sherman SI, Wirth LJ, Droz JP, et al: Motesanib diphosphate in progressive differentiated thyroid cancer. 

For Melanoma Patients, Recurrence-Free Survival Improves With Pegylated Interferon Therapy

The use of adjuvant pegylated interferon alfa-2b for resected stage III melanoma results in significant improvement in recurrence- free survival, according to investigators from Erasmus University Medical Center, Rotterdam, Netherlands and other European researchers for the EORTC Melanoma Group. These results were based on a randomized phase III trial involving more than 1,250 patients.

The study participants were randomly assigned to receive an induction dose of pegylated interferon alfa-2b (N = 627) 6 μg/kg/ week for eight weeks followed by a maintenance dose of 3 μg/kg/week, with the intent to treat for up to five years. A total of 629 patients were assigned to the observation group (controls).

Patients were treated with pegylated interferon alfa-2b for a median of 12 months. Individuals in the interferon group experienced 328 melanoma recurrences by a median of 3.8 years of follow-up compared with 368 recurrences in the observation group (hazard ratio, 0.82; 95% CI, 0.71-0.96; 

 = .01); the recurrence-free survival at four years was calculated to be 45.6% and 38.9%, respectively. No difference in the overall survival was observed between the two groups.

Two hundred forty-six patients (40%) were found to have grade 3 adverse events in the treatment group compared with 60 (10%) in the control group. Grade 4 adverse events occurred in 32 (5%) and 14 (2%), respectively. For the patients in the interferon group, fatigue (97 patients, 16%), hepatoxicity (66, 11%), and depression (39, 6%) were the most common grade 3 or 4 adverse events. Treatment was halted in 191 (31%) of patients because of toxicity.

Although the absolute difference in recurrence- free survival is not large, it does represent a significant and sustained effect for patients with stage III melanoma by treatment with adjuvant pegylated interferon alfa-2b, acknowledged the researchers. However, they did note the relatively high rate of grade 3 adverse events in patients taking this treatment.

Eggermont AM, Suciu S, Santinami M, et al: Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: Final results of EORTC 18991, a randomised phase III trial.

Induction Therapy for Patients With Anal Canal Carcinoma

Most patients with anal canal cancer who have large squamous cell tumors and lymph node involvement have a poor prognosis. American researchers from multiple centers have conducted a noncontrolled, nonrandomized trial to determine the safety and efficacy of an induction fluorouracil (FU)-based chemotherapy regimen with concurrent radiation.

Subjects with previously untreated T3 or T4 anal canal cancers, widespread nodal involvement, or both were given two 28-day cycles of induction therapy with infused FU plus cisplatin and then two 28-day cycles of FU plus mitomycin C with concurrent splitcourse radiation. Patients with persistent primary site disease or bulky N2 or N3 disease upon presentation received a third cycle of FU plus cisplatin with radiation boost.

Protocol therapy was given to 45 patients considered assessable. Generally, individuals tolerated the treatment well. The most common toxicities were gastrointestinal and hematologic. Eight complete and 21 partial responses were achieved with induction chemotherapy. A complete response occurred in 37 of the 45 high-risk patients (82%) after induction, combined-modality, and boost therapy.

The oncology researchers noted that after a follow-up period of four years, 68% of the patients are still alive, 61% are disease-free, and 50% are disease-free and not using a colostomy. The majority of patients with poor-prognosis anal canal cancer achieved disease control using this combined-modality approach.

Meropol NJ, Niedzwiecki D, Shank B, et al: Induction therapy for poor-prognosis anal canal carcinoma: A phase II study of the cancer and leukemia group B (CALGB 9281).

Ovarian Cancer Treatment With Imatinib Mesylate

Does imatinib, which is highly effective for chronic myelogenous leukemia, also have a role in the treatment of other cancers? Researchers from the Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, have tested the activity and tolerance of imatinib in patients being treated for recurrent or persistent epithelial ovarian or primary peritoneal carcinoma.

In this noncontrolled experiment, the investigators evaluated the six-month progression-free survival (PFS) associated with imatinib monotherapy, and performed mutational analysis of several molecular markers related to imatinib targets to determine if any predicted tumor response to treatment.

Of the 56 patients who were evaluated, nine (16%) did not demonstrate any disease progression after six months progression-free, and one patient (2%) was considered a complete responder. However, median PFS was 2 months, with an overall median survival of 16 months. Common grade 3 and 4 adverse events included pain, GI, dermatologic effects, neutropenia, and electrolyte disturbances.

All tumors expressed at least one imatinib target (platelet-derived growth factor [PDGFR]-alpha, PDGFR-beta, or KIT); all three receptors were expressed by a majority of the tumors. Shorter PFS was related to greater p-AKT and PDGFR-beta expression.

Also associated with worse outcomes were higher pretreatment concentrations of vascular endothelial growth factor and PDGF-alpha and -beta. The investigators found none of the markers to predict positive outcomes with imatinib.

The researchers concluded that imatinib has only minimal single-agent activity in patients with recurrent ovarian or primary peritoneal cancer.

Schilder RJ, Sill MW, Lee RB, et al: Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: A Gynecologic Oncology Group Study.

Clinical Trial Reports: May 28, 2010

Electronic Health Records Are an Elusive Goal For Office-Based Physicians

Without computerized medical records that can be transferred and viewed from one treating physician to another, experts doubt that we can advance the clinical quality and safety agenda in this country. Managed care organizations understand that electronic health records (EHRs) are the key to preventing drug—drug interactions, reducing duplicative medical testing, and better recording of patient allergies and comorbidity data, but they (and their contracted physicians) struggle with the cost of implementing these systems. As a result, according to researchers, only a small proportion of office-based physician practices have adopted these systems.

In a 2008 survey of 2,758 physicians nationwide, only 4% reported that they had a “fully functional” electronic records system. Thirteen percent indicated that they used a “basic system” (Table). Three percent had purchased but not yet implemented their EHR. Of those with a fully featured EHR, 71% stated that it was integrated with their affiliated hospital’s system. In comparison, 56% of those with basic systems have synched theirs with EHRs at their affiliated hospital.

Costs of purchase and implementation and concerns about return on investment were critical barriers to adoption, even though survey respondents indicated that EHRs would be expected to improve quality of patient care. Unfortunately, the researchers did not provide differential results based on practice specialty; they did find that primary care practices tended to utilize EHRs more frequently than specialty practices, but the responding numbers were small. It would be interesting to better understand the adoption of EHRs in community oncology practice.

In related news, the federal government acknowledged the importance and the cost of implementing electronic prescribing in its recent wrangling over the Medicare physician pay cut that was ultimately passed by Congress into law. Part of that legislation directs the Centers for Medicare & Medicaid Services to pay additional money to physicians who utilize electronic prescribing. During 2009 and 2010, physicians treating Medicare patients will get an extra 2% in their reimbursements when using E-prescribing in order to defray the costs of the system, which is estimated at $3,000 per doctor.

Freking K: Health officials tout computer prescribing.

Change in Medicare Reimbursement Does not Result in Worse Access to Chemotherapy

When the Medicare Modernization Act of 2003 ushered in the switch to reimbursement based on average sales price (ASP) methodology, it was assumed that physicians would refer patients to other facilities to receive parenteral therapies they had been administering in their office. If that was the case, it was hypothesized that patients would find it more difficult to obtain needed parenteral treatments.

Journal of the American Medical Association

 demonstrates that patient access has been largely unaffected by the switch from “buyand- bill” incentives. Using samples from Medicare claims from the Centers for Medicare & Medicaid Services, researchers from Duke University, Durham, North Carolina, evaluated more than 5,000 incident cases of five cancer types (breast, colorectal, or lung cancer; leukemia; or lymphoma) each year from 2003 through 2006.

They found that for each year, before and after the reimbursement provisions of the Act were implemented, 70% of the patients received parenteral treatment in the physician’s office. They did find that the proportion of patients receiving chemotherapy in hospitals decreased from 2003 to 2006 (from 10.2% to 8.8%, respectively) but the proportion who received their parenteral chemotherapy in outpatient infusion centers increased slightly over that period (from 21.1% to 22.5%). These changes were statistically significant, but from 2003 to 2006, 68.7% of the patients received office-based infusions or injections. Average waiting times to receive initial chemotherapy after diagnosis increased by 0.88 days in 2006 compared with 2003. The researchers did a geographical analysis of the distance between where patients’ were given their chemotherapy relative to their home address, and they found that patients distance to receive chemotherapy increased by one mile compared with before implementation of the new ASP reimbursement formula.

They concluded that Medicare patients’ access to injectable or infusible chemotherapies were not widely affected by the changes in reimbursement mandated by the Medicare Modernization Act.

Shea AM, Curtis LH, Hammill BG, et al: Association between the Medicare Modernization Act of 2003 and patient wait times and travel distance for chemotherapy. JAMA 2008;300:189-196.

The value of a biologic medication is often difficult to determine, as they are usually prescribed for limited groups of patients and manufacturers set relatively high prices to offset long and challenging research and manufacturing costs. This is frequently the case for oncology biologic medications, as they produce incremental benefits to extend life or at least progression-free survival. The United States does not have a single agency that is responsible for reviewing overall value of drug benefits, but Great Britain does.

Its National Institute for Clinical Health and Excellence (NICE) gave a thumbs down to bevacizumab for first-line use in lung and breast cancer in a late June decision. Although not a Food and Drug Administration—type authority, NICE wields a different and effective weapon: It provides recommendations to the National Health Service (NHS) to authorize reimbursement of a product based on its value. In the care rationing system of the NHS, it is all about value.

The Institute pointed out that the product’s manufacturer did not provide evidence on bevacizumab’s clinical and cost effectiveness. Apparently, Roche knew it was a no-win proposition. A spokesman for Roche UK confirmed that it did not provide breast cancer and lung cancer information to NICE, because they knew it could not meet the rigid limit cost effectiveness set by NICE.

NICE rejects cancer drug in clash with Roche. Reuters June 26, 2008.

Medicare Pay-for-Reporting Program Sends $36 Million in Bonuses to Participating Physicians

Medicare’s first foray into pay-for-performance programs is a phased project that seeks to get physicians used to reporting quality data. This “pay-for-reporting” initiative, as some have referred to it, the Physician Quality Reporting Initiative (PQRI), paid out its first bonuses for 2007, reported the Centers for Medicare & Medicaid Services (CMS) in July.

According to CMS, 56,700 clinicians provided clinical quality data that met designated standards and would receive $36 million in payments by August. The average payments to individual health care professionals was more than $600, and the average to group practices topped $4,700. The largest payment was to a physician practice, earning nearly $206,000 in bonuses.

The PQRI program will pay as part of the 2008 program a 1.5% financial bonus, as it did for 2007. The 2008 program includes 119 quality measures and two structural measures (whether electronic health records and/or electronic prescribing is utilized). Information about participation may be obtained from www.cms.hhs.gov/pqri.

Medicare Quality Reporting Initiative Pays Over $36 Million to Participating Physicians From the 2007 PQRI Reporting Period (press release). Centers for Medicare and Medicaid Services, July 15, 2008.

Low Insurance Caps Continue to Plague Health Policies

No one would blame any patient with cancer who worries that their health care costs may threaten to reach the maximum benefit allowed by their health insurance policy. The costs of biologic medications, imaging tests, surgery, and supportive agents can easily exceed a few hundred thousand dollars, and costs of more than $1 million are not rare.

, Robert Zirkelbach, a spokesperson for the health industry trade group America’s Health Insurance Plans, stated, “I think the discussion needs to move into why do some health care services cost hundreds of thousands of dollars and what can we do to address the issue?”

According to the Henry J. Kaiser Family Foundation, 22% of employer-sponsored health plans employ lifetime benefit maximums of $2 million or less. Only 1% offered plans with benefit caps at $1 million or less.

Still, $1 million does not go as far as it used to. If a health benefit had a maximum of $1 million in 1970, that would have to be $10 million today, to provide similar protection.

Murphy T: Low health insurance caps leave patients stranded. 

Reimbursement and Managed Care News: May 28, 2010

Influenza epidemics occur every year in the United States, typically beginning in the late fall or winter and concluding during the spring.

 During the 2006—2007 season, influenza circulated at epidemic levels for about 14 weeks and peaked during February, the month most frequently associated with peak activity over the past 31 influenza seasons.

 According to estimates from the Centers for Disease Control and Prevention (CDC), influenza has caused roughly 36,000 deaths and 226,000 hospitalizations annually.

 However, the rate of flu varies each year based on viral virulence and duration of circulation. Complications, hospitalizations, and death are most common in patients aged ≥65 years.

 In recent years, there has been a growing recognition among oncologists and other cancer care professionals of the importance of vaccination against influenza in patients with cancer.

For most people with cancer, vaccination for influenza is not only safe, but also a crucial part of staying as healthy as possible. Owing to their weakened immune system, patients with cancer are at high risk for infection with flu and pneumonia viruses, which can be lethal in these individuals. Yearly flu and pneumonia shots often prevent infection entirely and can lessen the severity of illness in those who do get sick.

Influenza viruses are divided into three types, designated A, B, and C. Influenza types A and B are responsible for epidemics of respiratory illness that occur almost every winter and are often associated with increased rates for hospitalization and death. Influenza type C differs from types A and B in some important ways. Type C infection usually causes either a very mild respiratory illness or no symptoms at all; it does not cause epidemics and does not have the severe public health impact that influenza types A and B do. Efforts to control the impact of influenza are aimed at types A and B.

Influenza type A viruses are divided into subtypes based on differences in two viral proteins called the hemagglutinin (H) and the neuraminidase (N). The current subtypes of influenza A are designated A(H1N1) and A(H3N2). Influenza A(H1N1), A(H3N2), and influenza B strains are included in each year’s influenza vaccine. In the years since its emergence, type A(H3N2) epidemics have caused more than 400,000 deaths in the United States alone, and more than 90% of these deaths have occurred among people age 65 and older.

Influenza type A viruses undergo two kinds of changes. One is a series of mutations that occur over time and cause a gradual change in the virus. This is called antigenic “drift.” This constant changing enables the virus to evade the immune system of its host, so that people are susceptible to influenza virus infection throughout life. This process works as follows: A person infected with influenza virus develops antibody against that virus; as the virus changes, the “older” antibody no longer recognizes the “newer” virus, and reinfection can occur The older antibody can, however, provide partial protection against re-infection.

The other kind of change is an abrupt change in the hemagglutinin and/or the neuraminidase proteins. This is called antigenic “shift.” In this case, a new subtype of the virus suddenly emerges. Type A viruses undergo both kinds of changes; influenza type B viruses change only by the more gradual process of antigenic drift.

CDC Recommendations For Influenza Vaccination

Influenza vaccination is the most effective method for preventing influenza virus infection and its complications, which may be severe. The CDC updated its recommendations regarding who should receive influenza vaccination in 2008.

 Current recommendations regarding annual vaccination in children/adolescents and adults are summarized in Table 1 and Table 2, respectively. It is important to note that patients with cancer may fall into several of the categories shown in the tables.

In 2008, the Advisory Committee on Immunization Practices (ACIP) of the CDC expanded its recommendations for influenza vaccination for school-aged children.

The ACIP-CDC now recommends that all children aged six months to 18 years receive annual influenza vaccination, beginning in 2008 if feasible, but beginning no later than during the 2009—2010 influenza season.

Since influenza viruses undergo frequent antigenic change, persons recommended for vaccination must receive an annual vaccination against the viruses known to be in circulation each year.

 trivalent influenza vaccine may be used for any person aged ≥6 months, including those with high-risk conditions. The 2008—2009 trivalent vaccine virus strains are A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like, and B/Florida/4/2006-like antigens.

Live, attenuated-virus vaccine is currently approved only for healthy, nonpregnant persons aged 5—49 years.

Influenza Vaccination Recommendations, 2008:

Children and Adolescents Aged Six months to 18 years*+

• Vaccination of all children aged six months —18 years should begin before or during the 2008–2009 influenza season if feasible, but no later than during the 2009–2010 influenza season. Vaccination of all children aged 5-18 years in a new ACIP recommendation.

• Children and adolescents at high risk for influenza complications should continue to be a focus of vaccination efforts as providers and programs transition to routinely vaccinating all children and adolescents. Recommendations for these children have not changed.

• Children and adolescents at higher risk for influenza complications are those: — Aged six months–4 years – Who have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological or metabolic disorders (including diabetes) – Who are immunosuppressed (including immunosuppression caused by medications or by human immunodeficiency virus) – Who have any condition (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration – Who are receiving long-term aspirin therapy who therefore might be at risk for experiencing Reye syndrome after influenza virus infection – Who are residents of chronic-care facilities – Who will be pregnant during the influenza season.

ACIP = Advisory Committee on Immunization Practices.

†Children aged <6 months should not receive influenza vaccination. Household and other close contacts (eg, daycare providers) of children aged <6 months, including older children and adolescents, should be vaccinated.

• Annual recommendations for adults have not changed. Annual vaccination against influenza is recommended for any adult who wants to reduce the risk for becoming ill with influenza or of transmitting it to others.

• Vaccination also is recommended for all adults in the following groups, because these persons are either at high risk for influenza complications, or are close contacts of persons at higher risk:

— Women who will be pregnant during the influenza season

— Persons who have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological, or metabolic disorders (including or metabolic disorders (including diabetes)

— Persons who immunosuppression (including immunosuppression caused by medications or by human immunodeficiency virus)

— Persons who have any condition (e.g., cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration

— Residents of nursing homes and other chronic-care facilities

— Household contacts and caregivers of children aged <5 years and adults aged ≥50 years, with particular emphasis on vaccinating contacts of children aged <6 months

— Household contacts and caregivers of persons with medical conditions that put them at high risk for severe complications from influenza.

*Recommendations of the Advisory Committee on Immunization Practices, 2008

According to the CDC, less than 30% of patients with high-risk conditions, including cancer, were vaccinated against flu in 2005.

 Table 3 shows flu vaccination coverage levels in persons with high-risk conditions, including cancer, by age. Data shown in the table were derived from the National Health Interview Survey and National Immunization Survey, US, 2005.

The results of a survey presented on October 27, 2007 at the 49th annual meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO) in Los Angeles (Poster 2641) highlight the poor flu vaccination coverage in patients with cancer specifically.

 About a third of patients who responded to an anonymous survey said they had not had a flu vaccination, according to Neha Vapiwala, MD, University of Pennsylvania, Philadelphia, PA, and one of the authors of the presented study.

The survey was completed by 214 consecutive cancer outpatients at the University of Pennsylvania from August 2006 to January 2007. Ninety-eight percent of the questionnaires were complete and usable for analysis. This was the first performed to evaluate whether patients with cancer are compliant with national vaccination guidelines. Patients who reported not receiving flu vaccine were asked further questions about the reasons why they didn’t receive it.

Key findings from the study were as follows

• Thirty percent of patients said they had never had the flu vaccine, and another 9% said they were not getting vaccinated yearly.

• About 60% of unvaccinated patients said they didn’t know they needed a flu shot.

• Among patients aged 50 and older—i.e., those recommended for a flu shot&mdash;33% had never been vaccinated.

• Among patients who got their shots, 66% said they heard about the vaccines from a health care provider other than one providing cancer care. Only ten% of patients were told about flu vaccine by an oncologist.

Dr. Vapiwala reiterated, “Despite being seen by many clinicians for their cancer care, only one in ten patients who actually got vaccinations said the shots had been recommended by their oncologist.”

When asked about potential reasons for the suboptimal flu vaccination in patients with cancer, Dr. Vapiwala explained, “It’s a communications gap. Oncologists tend to assume that vaccinations are being handled by the primary care provider, while the primary care physician may assume the opposite. It’s not clear to patients and it’s not clear to physicians necessarily who is responsible for what.”

Clearly, a key reason for not receiving flu vaccine was not knowing about the vaccine, thinking it was not needed, or not having it recommended by a physician. The issue is important because patients who have malignancies and who undergo cancer treatment are at greater risk of acquiring viral illnesses such as influenza. They also tend to have a more severe course and a more difficult recovery once they develop an infection.

For most people with cancer, vaccination for influenza is not only safe, but also a crucial part of staying as healthy as possible. Owing to their weakened immune system, patients with cancer are at high risk for infection with flu and pneumonia viruses, which can be lethal in these individuals. Yearly flu and pneumonia shots often
prevent infection entirely and can lessen the severity of illness in those who do get sick.

September 2008 | Oncology & Biotech News

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Clinical Trial Reports: May 28, 2010

Reimbursement and Managed Care News: May 28, 2010

Flu Vaccination in Patients with Cancer: Emerging Trends

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