It has been nearly 18 years since the first molecularly targeted therapy, rituximab (Rituxan), was approved for the treatment of patients with B-cell non-Hodgkin lymphoma, a development that helped launch a new era in cancer care.

Today, as scientific advances propel the oncology field forward with novel strategies aimed at genomic aberrations and biological processes, the first generation of targeted agents continues to form the backbone of treatment for the tumor types in which they were initially approved and to fulfill expanded roles in other malignancies.

As the year opens on a fresh season of discovery, OncologyLive asked experts in lymphoma, chronic myeloid leukemia, breast cancer, and non—small cell lung cancer to discuss the impact that the first targeted agents have had on these malignancies and the prospects for new therapeutic approaches that might improve upon the impressive gains made during the past two decades.

: Tactics for Improving Rituximab Regimens Vary With Subtype

The introduction of rituximab to the treatment of patients with non-Hodgkin lymphoma (NHL) in 1997 has doubled median survival to 10 years for individuals newly diagnosed with high-risk, low-grade follicular lymphoma and also has made a significant, although not as dramatic, impact in aggressive lymphomas, according to Andy Chen, MD, PhD. Rituximab is a genetically engineered murine/human monoclonal antibody directed against the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes.

Chen, who leads the lymphoma research group for the Knight Cancer Institute at Oregon Health & Science University (OHSU) in Portland, said approaches to improve upon established rituximab-containing regimens vary according to lymphoma subtype— with different degrees of success thus far. For B-cell NHL, the standard regimen had been R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) until recent years.

In 2012, German researchers demonstrated that pairing bendamustine (Treanda) with rituximab significantly improved progression-free survival (PFS) over R-CHOP (69.5 months vs 31.2 months, respectively) as first-line therapy among patients with indolent NHL subtypes, including follicular and mantle cell lymphoma (MCL).

 And in October 2014, the FDA approved bortezomib (Velcade) as part of a regimen that includes rituximab, cyclophosphamide, doxorubicin, and prednisone (VcR-CAP) for patients with previously untreated MCL, the first such treatment specifically indicated for this setting, based on a phase III clinical trial demonstrating a 59% relative improvement in PFS over R-CHOP.

“But this has all been progression-free survival so far,” said Chen. “There has been no overall survival benefit yet. It’s hard to show an overall survival (OS) benefit these days in low-grade lymphoma because the average survival of the high-risk patient in the rituximab era is over 10 years.”

In chronic lymphocytic leukemia (CLL), the emergence of the Bruton tyrosine kinase inhibitor ibrutinib (Imbruvica) and other targeted therapies has prompted efforts to combine a new agent with rituximab. Ibrutinib is approved for the treatment of patients with MCL or chronic lymphocytic leukemia (CLL) in relapse settings. Last year, the FDA also approved idelalisib (Zydelig), a PI3K-delta inhibitor, in CLL in combination with rituximab, and in relapsed follicular and small lymphocytic lymphoma.

“Low-grade lymphoid malignancies, particularly CLL, are further along in terms of novel and targeted therapies. A lot of those drugs that have worked well in low-grade lymphoma and CLL have not worked as effectively in aggressive lymphoma,” said Chen.

For aggressive lymphomas, researchers have had a more difficult time improving upon R-CHOP. Diffuse large B-cell lymphoma (DLBCL) is now divided molecularly into germinal center (GC) versus activated B-cell (ABC) subtypes, with significantly worse outcomes among patients with the ABC type who receive the standard R-CHOP therapy, Chen noted. He said researchers are experimenting with adding agents to the R-CHOP regimen such as ibrutinib, bortezomib, and lenalidomide (Revlimid) for ABC subtype DLBCL. Another approach involves seeking improvements to the chemotherapy component of the regimen, most notably dose-adjusted R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin).

Chen said there are indications that R-EPOCH may be more effective for some types of aggressive lymphomas than R-CHOP; a phase III clinical trial testing this hypothesis in DLBCL is currently under way.

 However, he said R-EPOCH is more cumbersome to administer in terms of dosing schedules and monitoring of blood counts, and therefore might not translate well into community settings. “We use it ourselves, but only for highly aggressive lymphomas like MYC-positive or double-hit lymphomas,” said Chen.

While most of these regimens remain anchored to rituximab, the possibility of a more potent replacement for targeting CD20 also is an important strategy under development. In 2013, the FDA approved obinutuzumab (Gazvya), a type II glycoengineered monoclonal antibody that selectively targets CD20, for the treatment of patients with previously untreated CLL in combination with chlorambucil after studies showed the regimen was superior to chlorambucil alone. In December, the label was updated to reflect results from the CLL11 trial indicating that obinutuzumab plus chlorambucil led to a median PFS of 26.7 months compared with 14.9 months with rituximab and chlorambucil (HR = 0.42; 95% CI, 0.33-0.54; P <.0001).

In lymphomas, the question of whether obinutuzumab can replace rituximab in chemotherapy regimens likely will be answered by two phase III trials: the GALLIUM trial5 in patients with untreated advanced indolent NHL and the GOYA trial6 in patients with treatment-naïve DLBCL.

“Going forward, there will always be an anti-CD20 antibody involved in the B-cell NHL treatment,” said Chen. “If obinutuzumab is shown in multiple phase III studies to be better than rituximab, then I think you’ll see a movement toward it. In part, it will also depend on the cost difference between obinutuzumab and rituximab—or future biosimilar&mdash;and what the magnitude of benefit is.”

Regardless of the outcome of any particular study, the need for new therapies for patients suffering from aggressive disease remains pressing, Chen stressed.

“Yes, these days in the R-CHOP era, we cure over 50% of aggressive lymphoma,” said Chen. “But there’s still a significant number of patients who are not cured. Those patients tend to relapse early, and the majority do not respond to standard second-line therapy and transplant. We have very poor treatment options for them.”

 Many Agents Follow Imatinib But Big Questions Remain

The development of imatinib (Gleevec) for patients with chronic myeloid leukemia (CML) is often considered one of the most important developments in the emergence of targeted therapies. The small molecule tyrosine kinase inhibitor (TKI), which Giants of Cancer Care award winner Brian L. Druker developed at OHSU, was approved in record time by the FDA in 2001 and now carries 10 indications in hematologic and other malignancies. In fact, oncology specialists last year ranked imatinib among the “Top 5 Advances in Modern Oncology” in an American Society of Clinical Oncology poll, not only because of its impact on the treatment of blood cancers but also because the agent helped point the way to attacking molecular mutations.

 Imatinib targets tyrosine kinases encoded by the BCR-ABL fusion gene, an abnormality known as the Philadelphia chromosome (Ph).

“Imatinib is an amazing model of a success story in cancer. In fact, before the era of imatinib, patients with CML used to live 6 to 7 years. They would get interferon and those who were lucky would get transplantation,” said Elias J. Jabbour, MD, an associate professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston. “With the era of imatinib, things have changed drastically. Today, somebody with CML can expect to have a normal lifespan on a drug.”

Today, clinicians have a field of BCR-ABL inhibitors from which to choose to treat patients with CML. The second-generation compounds dasatinib (Sprycel) and nilotinib (Tasigna) are both more potent BCR-ABL inhibitors than imatinib and are approved in frontline as well as relapse settings, Jabbour and colleagues noted in a recent review.8 In clinical trials, dasatinib has been more effective than imatinib in helping patients achieve complete cytogenetic response (CCyR), while nilotinib has outperformed imatinib in the rate of major molecular response. Bosutinib (Bosulif) and ponatinib (Iclusig) are second-line choices; ponatinib is designed to attack the BCR-ABL T315I point mutation, which promotes resistance to frontline TKIs. Although the newer frontline agents are more effective as upfront therapy, they have not outperformed imatinib in OS, Jabbour said.

“It’s hard to show improvement over imatinib therapy,” he said. “The question is, should we give everybody a new drug upfront? That is an unsolved question.”

Other important questions that remain unsettled include whether it is safe for patients who have achieved a CCyR to stop taking a TKI, how to address the resistance to therapy that develops in a significant proportion of patients, and financial problems that patients encounter in their ability to pay for daily imatinib and other TKIs.

Looking forward, Jabbour said researchers are focusing on targeting stem cells directly as a means of potentially effecting a cure for CML and of new combinations of imatinib with other agents such as the protein synthesizer omacetaxine mepesuccinate.

“All these are very important concepts but still far away,” Jabbour said. Meanwhile, Jabbour said clinicians treating patients with CML must remain vigilant even amid positive results. “While progress has been made, we should not underestimate [the disease],” he said. “We should not say, well patients are doing so great why not leave them on their own? We should really monitor them very carefully and make sure the patient is responding very well.”

HER2-Positive Breast Cancer: More Research Needed on Trastusumab, Novel Agents

In breast cancer therapy, improving upon the performance of trastuzumab (Herceptin) for HER2-positive tumors has proved to be a daunting challenge for researchers and drug developers. Since its initial approval in 1998, the humanized monoclonal antibody has substantially improved disease-free survival and OS in several treatment settings, and has transformed metastatic disease into a manageable chronic illness for many patients.

 T-DM1 (ado-trastuzumab emtansine; Kadcyla) was considered the likely successor to trastuzumab until drug developer Genentech announced in December10 that two regimens containing the agent failed to outperform the standard trastuzumab plus chemotherapy combination in the phase III MARIANNE trial.

	T-DM1 is an antibody-drug conjugate that links trastuzumab with the microtubule inhibitor DM1, a maytansine derivative, to deliver both the anti- HER2 agent and chemotherapy directly to the cancer cells. In 2013, the FDA approved the drug as a single-agent treatment in the second-line setting for patients with HER2-positive metastatic breast cancer, and the MARIANNE trial was an attempt to move T-DM1 into a frontline setting for women with advanced, HER2-positive disease.

The disappointing results surprised Edith A. Perez, MD, the lead investigator in the MARIANNE trial, given the drug’s performance in preclinical studies and early clinical trials. In the three-arm trial, patients were randomized to T-DM1 plus or minus pertuzumab (Perjeta) or trastuzumab plus either docetaxel or paclitaxel. The novel therapeutic approaches resulted in PFS rates similar, but not superior, to the standard arm, according to Genentech. Specific findings have not yet been released.

“T-DM1 is an excellent drug in the portfolio of therapies for patients with HER2-positive metastatic breast cancer,” said Perez, deputy director at large for the Mayo Clinic Cancer in Florida. “It’s still there. Whether T-DM1 will substitute for trastuzumab and chemotherapy, I think it will require [us] to look at the data in detail to try to figure out the benefit ratio. Now we know there’s noninferiority, so there are other issues we’ll have to look at in detail.”

Overall, Perez said much more research is needed not only to further develop new therapies, but also to better elucidate trastuzumab. “We are trying to understand better how trastuzumab works,” Perez said. “Even though this drug has been available now for essentially 15 years, we’re still doing some work in identifying the real benefits of this drug and also identifying molecular markers to understand who benefits from trastuzumab.”

To that end, Perez has been investigating the correlation between levels of stromal tumor-infiltrating lymphocytes (S-TILs) and likelihood of disease recurrence among women with HER2-positive breast cancer treated with chemotherapy alone. Early analysis indicates that high TIL levels may function as a biomarker to identify patients for whom optimal treatment might be chemotherapy alone, without HER2-targeted therapy.

Similarly, Perez and colleagues have succeeded in confirming that adjuvant trastuzumab added to chemotherapy for 1 year should be the standard of care for women with early-stage HER2-positive breast cancer.12 The addition of trastuzumab led to a 37% relative improvement in OS and a 10-year OS rate of 84%.

“One of the critical issues related to the use of adjuvant therapy for patients with any cancer, including breast cancer, is whether the benefits we observe in the short term are maintained in the long term, especially related to survival,” said Perez. “We had demonstrated that in the short term, trastuzumab improved survival. Now we have 10-year data showing that the results are very solid.”

Another important study for the HER2-positive patient population is the phase III APHINITY trial, which is testing whether the combination of trastuzumab, pertuzumab, and a chemotherapy regimen, which was recently approved by the FDA for neoadjuvant therapy, will improve invasive disease-free survival in approximately 4800 patients who have undergone surgery for HER2-positive breast cancer. Results are expected in 2016. Meanwhile, Perez said improvements in the molecular targeting of HER2 through novel agents, such as bispecific antibodies, are an important goal.

“Many companies are trying to find better targeting of the HER2 protein and ways to modify the molecular structure to have these drugs that not only bind better to HER2 but also enhance the immune activation that is first associated with these monoclonal antibodies,” Perez said.

Non—Small Cell Lung Cancer: New EGFR Inhibitors Suggest Potential for Better Outcomes

The recognition that abnormal epidermal growth factor receptor (EGFR) activity can promote non—small cell lung cancer (NSCLC) led to the FDA approval of two TKIs targeting the mutation: gefitinib (Iressa) in 2003 and erlotinib (Tarceva) in 2004.

The introduction of these agents meant a new paradigm for treating patients with NSCLC, particularly as understanding of EGFR mutations was refined, and helped pave the way for targeting other aberrations such as ALK and ROS1 translocations.

“EGFR inhibitors have really changed the way we treat EGFR-mutated lung cancer,” said Thomas J. Lynch Jr, MD, the director of Yale Cancer Center and a pioneer in the use of EGFR molecular testing. “For patients who have mutations—which is 13% of patients in North America&mdash;these drugs offer less toxicity and better activity than conventional chemotherapy offers.”

Erlotinib has demonstrated OS and PFS benefits in several treatment settings in NSCLC clinical trials, but AstraZeneca took gefitinib off the market in the United States in mid-2005 after the agent failed to reach those benchmarks in studies that followed its initial accelerated approval.13 In December, AstraZeneca announced that the FDA is reviewing the company’s new drug application for gefitinib as monotherapy for first-line treatment of advanced or metastatic EGFR-mutated NSCLC.

At the same time, the development of EGFR inhibitors continues to evolve with agents more specifically targeted to certain points of the mutation. In 2013, the FDA approved afatinib (Gilotrif) for first-line treatment of patients with metastatic NSCLC whose tumors harbor EGFR exon 19 deletions or exon 21 (L858R) mutations. The agent is an irreversible TKI.

Two promising novel agents in development are rociletinib (CO-1686) and AZD9291, EGFR inhibitors that selectively target the T790M resistance mutation. Both agents have gained the FDA’s breakthrough therapy designation.

Lynch said the emerging agents are designed to more specifically target the molecular mutation, resulting in fewer toxicities, such as the rash and diarrhea that are most bothersome to patients. “By being designed against a mutated receptor, you have fewer side effects because you have less inhibition of wild-type EGFR and you have greater activity against the EGFR-mutated receptor—more antitumor activity, less side effects,” he said. “It delivers a better drug to patients. The future is for the use of third-generation drugs in patients who are mutation-positive.”

The most pressing problem with EGFR-targeted therapies in NSCLC, however, remains the resistance that develops to therapy, Lynch said.

“Third-generation [agents] may be able to tackle resistance partially, but it’s not entirely clear that they would be able to overcome it completely,” he said. “We just don’t know yet.”

			Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): updated results from the StiL NHL1 study. J Clin Oncol. 2012;30(suppl; abstr 3).

			FDA approves Velcade (bortezomib) for injection for previously untreated patients with mantle cell lymphoma [press release]. Cambridge, MA: Millennium: The Takeda Oncology Company; October 9, 2014.

			NIH Clinical Trials Registry. www.ClinicalTrials.gov. NCT00118209.

			FDA approves Gazyva (obinutuzumab) supplemental biologics license application with new data in previously untreated chronic lymphocytic leukemia [press release}. South San Francisco, CA: Genentech. December 24, 2014.

			NIH Clinical Trials Registry. www.ClinicalTrials.gov. NCT01332968.

			NIH Clinical Trials Registry. www.ClinicalTrials.gov. NCT01287741.

			The top 5 advances in modern oncology. American Society of Clinical Oncology website. http://cancerprogress.net/ top-5-advances-modern-oncology. Accessed January 5, 2015.

			Mathisen MS, Kantarjian HM, Cortes J, Jabbour EJ. Practical issues surrounding the explosion of tyrosine kinase inhibitors for the management of chronic myeloid leukemia [published online June 12, 2014]. Blood Rev. 2014;28(5):179-187.

			Sledge GW, Mamounas EP, Hortobagyi GN, et al. Past, present, and future challenges in breast cancer treatment [published online June 2, 2014]. J Clin Oncol. 2014;32(19):1979-1986.

			Genentech provides update on phase III MARIANNE study in people with previously untreated advanced HER2-positive breast cancer [press release}. South San Francisco, CA: Genentech. December 18, 2014.

			Perez EA, Ballman KV, Anderson SK et al. Stromal tumorinfiltrating lymphocytes (S-TILs): in the Alliance N9831 trial S-TILs are associated with chemotherapy benefit but not associated with trastuzumab benefit. Presented at: 2014 SABCS; December 9-12, 2014; San Antonio, TX. Abstract S1-06.

			Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2—positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831 [published ahead of print October 20, 2014]. J Clin Oncol. 2014;32(33):3744-3752.

			FDA approval for gefitinib. National Cancer Institute. http://www.cancer.gov/cancertopics/druginfo/fdagefitinib. Accessed January 5, 2015.

Articles

OncologyLive asked experts in lymphoma, chronic myeloid leukemia, breast cancer, and nonâ€“small cell lung cancer to discuss the impact that the first targeted agents have had on these malignancies and the prospects for new therapeutic approaches.

Moving Beyond Targeted Therapy Stalwarts: Experts Weigh In on Four Tumor Types

The FDA’s calendar for making decisions on new oncology drugs and indications is taking shape for 2015, and the clock is ticking on at least 13 applications for novel agents and new therapeutic settings for existing drugs.

Although more than 750 oncology medicines and vaccines are in development according to the Pharmaceutical Research and Manufacturers of America, only a fraction of those drugs will make it to the FDA for a final ruling in any particular year.

Here is a snapshot of therapies where applications have been completed and are under review, culled from company announcements about their research. The FDA does not disclose information about pending applications.

In some case, companies have identified deadlines by which the FDA has agreed to make a decision on whether to approve the drug, although the agency has been approving many oncology drugs ahead pf the goal dates. These key dates have been announced:

		February 22—The agency is expected to decide on a new indication for 

(Revlimid) plus dexamethasone in newly diagnosed patients with multiple myeloma who are not candidates for stem cell transplant, according to Celgene.

		March 8—A new drug application is pending for 

 for the treatment of invasive aspergillosis and invasive mucormycosis (also known as zygomycosis), a fungal infection predominantly occurring in immunocompromised patients, according to Astellas.

(Ibrance), an novel oral agent that targets CDK4/6, is under review as a first-line treatment in combination with letrozole for postmenopausal women with estrogen receptor—positive, HER2-negative advanced breast cancer who have not received previous systemic treatment for advanced disease, according to Pfizer. (The company said it has entered label discussions with the FDA for the drug).

, an oral multiple receptor tyrosine kinase inhibitor, is under consideration as a treatment for progressive radioiodine-refractory differentiated thyroid cancer, according to Eisai.

 (Imbruvica), a Bruton tyrosine kinase inhibitor, is under review as a treatment for patients with Waldenström macroglobulinemia, according to Pharmacyclics, which is developing the drug along with Janssen Biotech.

 (TVEC), an oncolytic immunotherapy, is under review for the treatment of regionally or distantly metastatic melanoma based on clinical trial data evaluating TVEC in patients with stage IIIB-IV melanoma that are not surgically resectable, according to Amgen.

These applications also are pending, with no specific decision dates announced thus far:

—This novel propylene glycol—free formulation of the longstanding anticancer agent is under consideration for two multiple myeloma indications: as a high-dose conditioning regimen prior to stem cell transplant and as a palliative treatment when oral therapy is not appropriate.

(GDC-0973)—An application has been submitted for the use of this novel MEK inhibitor in combination with vemurafenib (Zelboraf), a BRAF inhibitor, for patients with advanced melanoma that tests positive for a 

(Iressa)—AstraZeneca is seeking approval for the oral tyrosine kinase inhibitor as monotherapy for the first-line treatment of patients with advanced or metastatic 

-mutated non—small cell lung cancer. Gefitinib initially gained accelerated in the United States in 2003 but was withdrawn from the market two years later after faltering in confirmatory clinical trials.  

 (LBH589)—The pan-deacetylase inhibitor remains under review in combination with bortezomib and dexamethasone as a therapy for patients with previously treated multiple myeloma, according to Novartis.

 (LDE225) An application for this selective smoothened inhibitor has been submitted to the FDA as a treatment for patients with advanced basal cell carcinoma, Novartis has reported.

—A new drug application has been submitted for this nucleoside analog, which is a combination of trifluridine and tipiracil hydrochloride for the treatment of refractory metastatic colorectal cancer, Taiho Oncology has announced.

 (Yondelis)—This novel agent, which interferes with the repair mechanism of aberrant DNA, is under review as a treatment for patients with advanced soft tissue sarcoma, including liposarcoma and leiomyosarcoma subtypes, who have received prior chemotherapy including an anthracycline, according to Janssen.

The FDA's calendar for making decisions on new oncology drugs and indications is taking shape for 2015, and the clock is ticking on at least 13 applications for novel agents and new therapeutic settings for existing drugs.


13 Drugs to Watch in 2015

The ability to match individual patients with targeted cancer therapies based on the molecular profile of their tumors resulted in dramatically superior clinical outcomes in a phase I trial that builds support for personalized medicine and may help speed drug development.

The study, an initiative of the MD Anderson Cancer Center at the University of Texas in Houston, was among the encouraging research developments highlighted Friday as the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) got underway.

“The message is becoming increasingly clear: If we can figure out what molecular abnormality is driving the tumor and if we have a therapy that targets that  abnormality… we can get much better results than has customarily been the case,” Richard L. Schilsky, MD, a past president of ASCO who is chief of the Hematology-Oncology section at the University of Chicago Pritzker School of Medicine and deputy director of the university’s Comprehensive Cancer Center, said at a press briefing.

He said the results hold implications for clinical trials because better-matched therapies will display activity in phase I that typically is not seen until later phases, thus moving up the research timetable.

Investigators conducted molecular tests on the tumors of 1144 patients referred for phase I trials who had a variety of advanced cancers, particularly melanoma and colorectal cancers, and had undergone ≥4 previous therapies, said lead author Apostolia-Maria Tsimberidou, MD, PhD, associate professor in the Department of Investigational Cancer Therapeutics at MD Anderson. One to 4 aberrations were found in the tumors of 460 patients, or 40.2%.

Of those participants whose tumors exhibited 1 aberration, 291 patients were treated, with therapy matched to the molecular tumor abnormality for 175 patients, while 116 patients were treated with nonmatched therapies.

Tsimberidou said patients who received matched therapy had a partial and complete response rate totaling 27%, a median time to treatment failure (TTF) of 5.2 months, and a median survival time of 13.4 months.

By contrast, patients who received nonmatched therapy had a response rate of 5%, a TTF of 2.2 months, and a median survival of 9 months, Tsimberidou said.

Additionally, participants in the matched therapy group experienced a TTF of 5.2 months versus 3.1 months for their previous systemic therapy, while those in the nonmatched group saw no statistically significant difference.

For the matched group, regimens included 1 or more drugs that target molecular aberrations in genes such as 

“A therapy was considered to be matched to a patient’s tumor molecular abnormality if at least one of the drugs in the regimen was known to target the functionality of at least one of the patient’s molecular aberrations,” Tsimberidou said.

She said the results “further support the evidence of the effectiveness of the matched therapy and the superiority of the personalized medicine approach compared to the standard approach.”

Schilsky said the proportion of patients who benefit from a particular therapy in phase I is typically in the 5% range. “If you actually have a way of identifying which therapy is likely to work in a patient, you can substantially increase the likelihood of benefit for a patient even with advanced cancer, even in a phase I trial,” he said.

He said the study represents “a substantial improvement in drug development” even though 75% of the patients had no response.

Tsimberidou said in an interview there were a number of limitations to the study, which was conducted during a 4-year period. She said the study was exploratory, nonrandomized, and used archival tissue. The technology, she added, must be advanced to include more genes.

“We need to improve our technology and we need to discover targeted therapies,” she said.

For next steps, Tsimberidou said researchers should seek to “understand the emergence of resistance in patients treated with targeted therapy” as well as the impact of tumors with more than 1 aberration.

She said screening of patients for molecular aberrations should expand, noting that researchers at MD Anderson want to screen all patients who come to the center for treatment. The center sees about 30,000 patients a year, she noted.

The study, she said, “shows in a large scale that the personalized medicine approach is the future.’

Tsimberidou AM, Iskander NG, Hong DS, et al. Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center Initiative. 

Matching patients with targeted therapies based on molecular profile results in superior clinical outcomes 

By Anita T. Shaffer

Articles

Moving Beyond Targeted Therapy Stalwarts: Experts Weigh In on Four Tumor Types

13 Drugs to Watch in 2015

Molecular Profiling Boosts Targeted Therapies in Phase I Trial