In 1993, the National Institutes of Health (NIH) Revitalization Act mandated that women and members of racial and ethnic minorities be recruited for all NIH-sponsored clinical trials, with enough participants in subpopulations, particularly in phase 3 studies, to assess any valid differences in outcomes. Investigators seeking NIH grants were required to conduct outreach programs to help ensure that those goals were met.

But when it comes to minorities with cancer, the law has failed to deliver on its promise. Nearly 30 years after NIH sought to increase participation of minorities in clinical trials, a demographic imbalance remains. Of 4922 patients who participated in clinical trials that led to approvals for 18 new oncology drugs during 2020, 73% were White, 14% were Asian, 6% were Hispanic, and 5% were Black or African American, according to the FDA (

Figure. 2020 Clinical Trials Snapshot for New Oncology Drugs

During the past year, however, the COVID19 pandemic has shined a new light on health care disparities while racial justice protests have added an element of intensity to the discussions, experts say. A recent spate of developments illustrates fresh momentum for broadening access to clinical trials—and cancer care overall—for Black and Hispanic patients as well as other populations with lagging participation. These developments include the following:

A “road map” for designing multiple myeloma (MM) clinical trials that include more African American patients has been advanced by investigators from the Dana-Farber Cancer Institute in Boston, Massachusetts, in collaboration with experts from the FDA and the American Association for Cancer Research (AACR).

 The plan follows study findings that show the number of African American individuals enrolled in select MM trials declined by 3.5% from 2002 to 2011, even though incidence and mortality rates for the malignancy are higher than they are for White patients.

A massive COVID-19 relief and government funding package that Congress passed in December 2020 will require state Medicaid programs to cover routine patient costs for participation in qualifying clinical trials, including for cancer indications, starting in 2022. The lack of Medicaid coverage has impeded recruitment of minorities and the poor.

In September 2020, AACR released its first comprehensive report, which describes health care inequities and serves as a call to action for patients with cancer, including expanding clinical trial enrollment among minorities.

New models for improving access to clinical trials for minorities include hospital partnerships with community centers and clinical practices to treat patients in the areas where they live to increase clinical trial participation.

, leading oncology experts say that the convergence of efforts represents progress for racial minorities and that, they believe, this time there will be no turning back.

“I think it’s changed,” said Kimlin Tam Ashing, PhD, founding director of the Center of Community Alliance for Research and Education and professor in the Department of Population Sciences at City of Hope Medical Center in Duarte, California. “I think it’s multiple factors, particularly the Black Lives Matter movement and COVID-19. I think the whole country, the whole world has come to a deeper consciousness-raising and the sense that we have to do something. We cannot ignore this and say this is somebody else’s responsibility.”

The death toll from COVID-19 in the United States has surpassed the 570,000 mark, but the disproportionate impact on minorities is pronounced. The risk of COVID-19 hospitalization and death is 2.8 and 1.9 times higher, respectively, for Black or African American non-Hispanic individuals than it is for White individuals and 3.0 and 2.3 times higher, respectively, for Hispanic or Latino persons. “Race and ethnicity are risk markers for other underlying conditions that affect health, including socioeconomic status, access to health care, and exposure to the virus related to occupation, eg, frontline, essential, and critical infrastructure workers,” according to the CDC.

Such statistics cast renewed attention on disparities in cancer care. Overall, progress has been made in narrowing the gap in the cancer death rate, which was 33% higher in 1990 for African American vs White individuals to 14% higher in 2016, according to the AACR report; but much work remains to be done.

 The risk of dying from prostate cancer is 111% higher for African American men than it is for White men, and African American women have a 39% higher risk of dying from breast cancer than White women. Also, when it comes to leukemia, Hispanic children and adolescents are 20% and 38% more likely to develop the disease, respectively, than White children and adolescents.

The task of making clinical trial populations more inclusive is complicated by a variety of factors, including trial availability, restrictive eligibility criteria, and the logistics of taking time off from work, the AACR report noted.

Moreover, concerns about inclusion of racial minorities in clinical trials are played out against a backdrop of broader issues about the gap between study populations and real-world patients with cancer. One study found that enrollment in a clinical trial for first-line therapy markedly favors patients who are younger and have fewer comorbidities than the population of patients with cancer as a whole, as well as those with private insurance, and those who obtain treatment at academic medical centers.

In some respects, the disparities in clinical trial enrollment are a result of business pressures that drive pharmaceutical companies to test novel drugs in homogenous populations with fewer confounding factors at high-enrolling sites.

Additionally, the increasingly global nature of oncology drug development may worsen the minority enrollment gap in the United States, investigators found. In a study of patient enrollment in 49 global trials supporting 35 FDA drug approvals from 2015 through 2018 with race data available, Black patients made up only 2.5% of participants (range, 0%-10%). In 21 trials with both race and accrual location data available, 64% of patients were from outside the United States.

One of the more concrete proposals aimed at improving racial imbalances in clinical trials is getting underway in the MM research community as leading investigators seek to extend the benefits of novel treatments to underrepresented populations.

“We’ve had a paradigm shift and a marked improvement in outcomes of patients due to the development of multiple novel treatments,” Kenneth C. Anderson, MD, a 2014 Giants of Cancer Care

 award winner in the myeloma category, said in an inter-view. “It turns out not all patients have shared equally in the progress.”

Compared with White individuals, African American persons are more than twice as likely to receive a diagnosis of MM (15.9 vs 7.5 cases per 100,000 population) and to die from the disease (5.6 vs 2.4 myeloma deaths per 100,000). From 1973 to 2005, the 5-year relative survival rate increased from 26.3% to 35.0% for White Americans, a statistically significant improvement (

 < .005), compared with an increase from 31.0% to 34.1% for African American people. An analysis of 9 large MM trials conducted by National Cancer Institute cooperative groups showed that enrollment of African American participants declined to 13% during 2002 to 2011 from 16.5% in the prior decade.

Findings from other studies show that a more racially diverse trial population may yield a different outcome. For example, patients with MM of high African ancestry are more likely than those with high European background to harbor immunoglobulin heavy-chain translocations on chromosome 14, specifically t(11;14) and the high-risk t(14;16) or t(14;20) abnormalities.

This could have therapeutic implications for patients. In the phase 3 BELLINI trial (NCT02755597), the benefit of adding venetoclax (Venclexta) vs placebo to bortezomib (Velcade) and dexamethasone in patients with relapsed or refractory MM was observed only in those participants with t(11;14) and high BCL2 expression.

Anderson, who is studying venetoclax in patients with MM and t(11;14), sees the biomarker-driven emphasis as a noteworthy implication of more diverse clinical trial populations. “That’s a major opportunity to carry out clinical trials of this novel agent that are solely or certainly enriched by African American patients,” said Anderson, the Kraft Family Professor of Medicine at Harvard Medical School and director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at Dana-Farber Cancer Institute.

New recommendations to make MM trials more racially inclusive grew out of a workshop involving Anderson, who heads the AACR’s regulatory science and policy subcommittee, and FDA officials. 

Before clinical trials are approved, sponsors should consider expanding cohorts with broader eligibility criteria, drafting a specific diversity study plan, appointing a diversity officer for phase 2 and 3 studies, and designing trials that cover disease subtypes and features most commonly seen in African American individuals.

The plan, which also includes postapproval recommendations, could be applied to other groups and diseases, investigators noted. “Indeed, it is the hope of everyone who contributed to this initiative that these recommendations will lead to a more inclusive, ‘real world’ drug development paradigm,” the authors wrote.

Underrepresentation of minorities in clinical trials comes at the cost of not knowing whether treatment effectiveness and adverse effects are the same for their populations as for White patients. For instance, the patient’s immune status is believed to have an impact on the efficacy of immunotherapy. However, a recent analysis showed that the percentage of Black or African American patients ranged from 0% to 4% in clinical trials that led to approvals of immune checkpoint inhibitors involving 6 cancer types.

Additionally, disparities for minority participation have significant overlap with imbalances for other subgroups. In a study of outcomes for 41,109 patients who participated in large phase 2 and phase 3 trials from 1985 to 2012, participants from areas with the highest socioeconomic deprivation had worse outcomes compared with those from the most affluent areas for overall survival (HR, 1.28, 95% CI, 1.20- to 1.37; 

 < .001), progression-free survival (HR, 1.20; 95% CI, 1.13-1.28; 

 < .001), and cancer-specific survival (HR, 1.27; 95% CI, 1.18-1.37; 

Such findings illustrate why it was so critical for legislation requiring Medicaid to cover routine costs for patients participating in clinical trials, said Karen Winkfield, MD, PhD, who recently was named executive director of the Meharry-Vanderbilt Alliance, a strategic partnership between Meharry Medical College, a historically Black institution, and Vanderbilt University Medical Center, both in Nashville, Tennessee.

“This is not just race-ethnicity,” Winkfield said in an interview. “This is poor people, rural people.”

The AACR report used contributions from experts throughout the oncologic f ield to propose a blueprint for addressing health disparities. Among the recommendations were improving minority representation in clinical trial enrollment—including reduction of certain restrictive eligibility criteria—improving screening and early detection of cancers, conducting diversity- focused training and career development programs, and increasing diversity within the clinician pool.

Years of underrepresentation of African American and Hispanic participants in clinical trials has taken a cumulative toll as far as lack of data on how they might be affected by certain treatments. A 2009 analysis found that, despite the requirements of the NIH Revitalization Act of 1993, racial and ethnic groups were scarcely represented in genomic studies: 96% were carried out in populations of European descent. Although samples in the proportion of genome-wide association studies from underrepresented populations had risen to 19% when the issue was revisited in 2016, most of the increase was from Asian ancestry samples, with other ethnic groups experiencing minimal increase (from 1% to 4%).

“There’s so much we need to learn in this area,” said Edith A. Perez, MD, the 2014 Giants of Cancer Care

 award winner in the community outreach category, the Serene M. and Frances C. Durling Professor of Medicine at Mayo Clinic College of Medicine in Jacksonville, Florida, and vice chair of the Alliance for Clinical Trials in Oncology. “But the good thing is that the increased discussion in this topic is directly translating into action like I don’t remember seeing in the past.”

Broadening eligibility criteria overall is another key strategy to improve participation of minorities in clinical trials. In February, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research issued new recommendations in 5 specific areas: treatment washout periods, concomitant medications, prior therapies, laboratory reference ranges and test intervals, and patient performance status (

). The groups’ previous effort to expand trial eligibility resulted in the FDA revising its guidance for patients with brain metastases, minimum age for enrollment, HIV status, organ dysfunction, and prior or concurrent malignancies.

Table. Recommendations for Expanding Clinical Trial Eligibility

“Clinical trial access must be recognized as a health equity issue,” Lori J. Pierce, MD, FASTRO, FASCO, a professor and vice provost for academic and faculty affairs at the University of Michigan who is president of ASCO, said in announcing the new recommendations. “Overly restrictive eligibility criteria without scientific justification has led to an underrepresentation of older adults, racial/ ethnic and sexual/gender minorities, and patients with well-managed comorbidities.”

More focus should be placed on needlessly excluding patients due to comorbidities, Perez said. “Patients are being excluded for various reasons, including age, because it’s associated with comorbidities and concern about their impact and safety,” she said. “But we’ve learned those factors are really irrelevant.”

Contemporary Clinical Trials Communications

 by Jeanne M. Regnante, chief health equity and diversity officer at the LUNGevity Foundation in Bethesda, Maryland, and colleagues illustrates a path forward on improving diversity.

Fourteen leaders representing 8 cancer centers were asked how they achieved accrual rates for racial and ethnic minority groups of 10% to 50% in a 12-month reporting period. Among the findings were metrics for collection and reporting, routinely captured race and ethnicity data that are accessible to staff, and operational standards to support access and inclusion.

“I think when it becomes part of your standard practice, you don’t overthink,” Winkfield said. “You don’t say, ‘Oh, this is a Black person, and it’s going to be harder and they’re going to have issues.’ Or if you have a Spanish-speaking person, you don’t say, ‘Oh, it’s going to really tough. We’ve got to go get a translator.’”

The percentages of African American and Hispanic participants in trials for COVID-19 vaccines have been much more representative of the actual population, Winkfield noted. Outreach is critical to the African American community partly because of the Tuskegee Study of Untreated Syphilis in the Negro Male, in which hundreds of Black men were not given penicillin for the infection as part of a study even after it was established as a cure. The study continued for 40 years before being halted in 1972.

According to the CDC, Pfizer/BioNTech and Moderna, Inc had approximately 10% Black representation in their trials and 26.2% and 20.0% Hispanic representation, respectively. As of 2019, according to the US Census Bureau, 12.3% and 17.6% of the population 16 years and older were Black persons and Hispanic persons, respectively.

Ashing said clinicians’ frame of reference on Black patients’ reticence to participate in trials also needs to change. “Much of the literature from media and scientific literature describes this as medical mistrust,” she said. “I refrain from that terminology because I believe it is victim blaming. I prefer to frame it in terms of adaptive caution and concern because of our history of medical abuse.”

Some hospitals are taking innovative steps to reach out to the community, Ashing noted. City of Hope is developing partnerships with community clinics and hospitals as well as through their 29 community practices. These practices were developed in areas with high minority density and high numbers of underserved patients with cancer to provide access for prevention, screening, and studies and clinical trials. The use of telemedicine, brought about by the pandemic, may make significant inroads as well, she said.

Winkfield said the recruitment of racial and ethnic minorities to oncology teams is crucial. Patients feel more comfortable with doctors who look like them, she said. “What I usually get from Black patients is, ‘Oh my God, I can’t believe you’re a Black doctor.’ It’s different. There’s an instant rapport. I may be the first Black doctor they’ve ever seen.”

When White oncologists are not culturally aware and respectful enough of minority patients, the results can be tragic, Winkfield said. She described the case of a 28-year-old Black nurse with triple-negative breast cancer, the incidence of which is disproportionately higher in African American women. Winkfield advised her to undergo chemotherapy first and then surgery and radiation.

At their next visit, the woman explained to Winkfield that she had stopped the chemotherapy due to adverse effects and had gone straight to surgery. Winkfield said the oncologist, who was a White physician, dismissed the woman’s concerns rather than prescribe medication for the adverse effects and agreed to let her halt chemotherapy instead of insisting she stay the course.

Winkfield directed the woman back to chemotherapy, but it was too late. “I can’t say it was a direct result of the fact that she [went months without] chemotherapy, but that young woman ended up dying of brain metastases at age 29,” Winkfield said. “Those sorts of stories should never happen.”

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FDA. 2020 drug trials snapshots summary report. February 2021. Accessed April 19, 2021. 

New recommendations aim to eliminate racial bias in myeloma trials. News release. Dana-Farber Cancer Institute. February 17, 2021. Accessed April 19, 2021. 

Gormley N, Fashoyin-Aje L, Locke T, et al. Recommendations on eliminating racial disparities in multiple myeloma therapies: a step toward achieving equity in healthcare. 

. 2021;2(2):119-124. doi:10.1158/2643-3230.BCD-20-0123

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American Association for Cancer Research. Cancer Disparities Progress Report. September 16, 2020. Accessed April 19, 2021. 

Risk for COVID-19 infection, hospitalization, and death by race/ethnicity. CDC. Updated April 16, 2021. Accessed April 19, 2021. 

Zaorsky NG, Zhang Y, Walter V, Tchelebi LT, Chinchilli VM, Gusani NJ. Clinical trial accrual at initial course of therapy for cancer and its impact on survival. 

. 2019;17(11):1309-1316. doi:10.6004/jnccn.2019.7321

Nazah B, Mishra M, Pentz R, Owonikoko TK. Enrollment of racial minorities in clinical trials: old problem assumes new urgency in the age of immunotherapy. 

Tharakan S, Zhong X, Galsky MD. The impact of the globalization of cancer clinical trials on the enrollment of Black patients. 

. Published online March 8, 2021. doi:10.1002/cncr.33463

Kumar SK, Harrison SJ, Cavo M, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. 

. 2020;21(12):1630-1642. doi:10.1016/S1470-2045(20)30525-8

Unger JM, Moseley AB, Cheung CK, et al. Persistent disparity: socioeconomic deprivation and cancer outcomes in patients treated in clinical trials. 

. 2021;39(12):1339-1348. doi:10.1200/JCO.20.02602

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. 2017;8(4):255-266. doi:10.1007%2Fs12687-017-0316-6

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Regnante JM, Richie N, Fashoyin-Aje L, et al. Operational strategies in US cancer centers of excellence that support the successful accrual of racial and ethnic minorities in clinical trials. 

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About the USPHS syphilis study. Tuskegee University. Accessed April 19, 2021. 

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Articles

Nearly 30 years after National Institutes of Health sought to increase participation of minorities in clinical trials, a demographic imbalance remains. 

Clinical Trial Diversity Efforts Gain Steam

A recent wave of drug approvals for treating prostate cancer in earlier disease states coupled with genomic advances may help pave the way for a shift toward handling the malignancy as a chronic condition, according to Leonard G. Gomella, MD, FACS.

Starting with the February 2018 approval of apalutamide (Erleada), the FDA has carved out indications for patients with nonmeta-static castration-resistant prostate cancer (CRPC) and castration-sensitive prostate cancer, moving the use of androgen receptor (AR)–targeting agents earlier in the therapeu-tic paradigm.

Instead of focusing on treating men with late-stage prostate cancer, medical and urologic oncologists now have new options to attack the disease earlier in its progression, Gomella noted in an interview with 

“One of the concepts we talk about in prostate cancer is a shift to the left,” he said, referring to the treatment timeline. “Studies are investigating traditional agents used in advanced disease states and moving them to earlier disease states. In theory, [this would]suppress the progression of prostate cancer so instead of a life-threatening disease it becomes a chronically managed disease like diabetes or hypertension—that’s where a lot of the research is going,” Gomella said.

“The field is investigating drugs that may alter that trajectory of prostate cancer by doing more work on the cancer’s unique genetics and understand-ing the genetic triggers that you may be able to interact with earlier in the course of the disease to either slow progression or even prevent it from metastasizing. Or, once it’s metastasized, leave it there in a holding pattern.”

Gomella, a widely recognized expert in urologic cancers, is the Bernard W. Godwin Jr Professor of Prostate Cancer, and chair of the Department of Urology and senior director clinical affairs at Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania.

He will share his insights into new develop-ments in the field during the New York GU

Interdisciplinary Prostate Cancer Congress

 and Other Genitourinary Malignancies conference. Physicians’ Education Resource

) will host the meeting virtually on March 12-13.

Gomella will serve as program cochair, joined by Daniel P. Petrylak, MD, professor of medicine (medical oncology) and of urology and coleader of Cancer Signaling Networks at Yale Cancer Center in New Haven, Connecticut, as well as a 2017 Giants of Cancer Care

 award winner. The first day of the conference will feature presentations on urothelial carcinoma and renal cell carcinoma, and the second will focus primarily on prostate cancer.

Gomella’s involvement with New York GU™ reflects the leadership role that he has established during his nearly 40-year career in urology. Gomella helped pioneer the use of molecular analyses in prostate cancer through the development of reverse transcriptase–polymerase chain reaction for prostate-specific antigen (PSA) to detect circulating prostate cancer micro-metastases in the early 1990s.

 This work is considered the earliest concept of the “liquid biopsy” being used today. In addition, he led the urology effort for the 2017 Philadelphia Prostate Cancer Consensus Conference that resulted in the first multidisciplinary guidelines on genetic testing for prostate cancer.

“Dr Gomella has been a major force in urologic oncology,” said Robert Dreicer, MD, director of solid tumor oncology in the Division of Hematology/Oncology at the University of Virginia (UVA) School of Medicine and deputy director of the UVA Cancer Center in Charlottesville, Virginia. “He works in all the major urologic malignancies, but his work in prostate cancer involves translational genomics. He’s been a major contributor with genomics in predicting the risk of localized disease in the role of intervention. And he pioneered multidisciplinary management of prostate cancer. He’s really in the forefront of urologic oncology in 2021.”

Recent FDA Approvals of New and Expanded Indications in Prostate Cancer

 meeting will be brimming with new information about best practices and emerging research for each cancer type on the agenda, Gomella said. For example, Dreicer will discuss integrating next-generation antiandrogens and chemotherapy into treatment plans for patients with metastatic prostate cancer.

Several groundbreaking developments in prostate cancer that occurred during 2020 will be covered. These include approvals for the PARP inhibitors rucaparib (Rubraca) and olaparib (Lynparza), the first oral molecularly targeted therapies for this tumor type; relugolix (Orgovyx), the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist; and Gallium 68 PSMA-11 (Ga 68 PSMA-11), the first drug for positron emission tomography (PET) imaging of prostate- specific membrane antigen (PSMA)–positive lesions in men with prostate cancer.

The 2 recent PARP approvals for prostate cancer, which occurred within a 5-day period in May 2020, “are opening up a whole new spectrum of oral agents for the management of advanced prostate cancer,” Gomella said.

Rucaparib received accelerated approval for adult patients with metastatic CRPC with germline or somatic 

 mutations who have been treated with AR-directed therapy and a taxane-based chemotherapy. The decision was based on results from the single-arm TRITON2 trial (NCT02952534), in which rucaparib demonstrated an objective response rate of 44% (95% CI, 31%-57%) in 62 patients with measurable disease. Participants received rucaparib 600 mg orally twice daily along with a GnRH analog or had prior bilateral orchiectomy.

Olaparib is indicated for adult patients with metastatic CRPC harboring a germline or somatic mutation in a homologous recombination repair (HRR) gene, including 

, who have progressed following prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga). The drug was approved based on data from the phase 3 PROfound study (NCT02987543), in which patients were randomized 2:1 to olaparib at 300 mg twice daily (n = 256) or investigator’s choice of enzalutamide or abiraterone (n = 131). As in the rucaparib trial, all participants also received a GnRH analog or had prior bilateral orchiectomy.

Participants were divided into 2 cohorts based on mutation status: cohort A for those with mutations in 

 and cohort B for those with mutations in 12 other genes associated with HRR. Radiological progression-free survival (rPFS) in cohort A, the primary end point of the study, was a median of 7.4 months (95% CI, 6.2-9.3) among those who received olaparib versus 3.6 months (95% CI, 1.9-3.7) for patients who received investigator’s choice of therapy (HR, 0.34; 95% CI 0.25-0.47; 

 < .0001). The median overall survival was 19.1 months (95% CI, 17.4-23.4) with olaparib versus 14.7 (95% CI, 11.9-18.8) with investigator’s choice (HR, 0.69; 95% CI, 0.50-0.97; 

 = .0175). The median rPFS for olaparib in cohorts A plus B also was higher than for standard therapy (5.8 vs 3.5 months; HR, 0.49; 

“PARP inhibitors interfere with the ability of the malignant prostate cancer cell’s DNA HRR mutations to repair itself and continue to grow, so they are a very effective tool,” Gomella said. “PARP inhibitors are considered third-, or fourth-line therapies; these men must have failed other standard therapeutic interventions for metastatic castrate-resistant prostate cancer to be eligible for olaparib or rucaparib.”

The population of patients with advanced disease who could be eligible for PARP therapy represents a significant subset. Study f indings indicate that the prevalence of germline mutations in genes regulating DNA repair processes in men with metastatic prostate cancer is at least 11.8%, including 5.3% with 

 mutations. In men with localized high-risk disease, the incidence of HRR genes was 6%.

Additionally, the FoundationOne Liquid CDx assay has been approved as the companion diagnostic to detect relevant mutations for both PARP inhibitors. The next-generation sequencing tool is a liquid biopsy capable of analyzing circulating cell-free DNA isolated from plasma derived from peripheral whole blood of patients with cancer.

“Developments in biomarkers and genetics have been explosive,” said Gomella, who will be giving a presentation on this topic. “We now have circulating tumor DNA that can be evaluated in patients with prostate cancer to determine genetic susceptibility to new medications. This is a big breakthrough.”

Relugolix, approved in December 2020 for patients with advanced prostate cancer, is the most recent arrival on the scene. The FDA based its decision on findings from the phase 3 HERO trial (NCT03085095), in which relugolix demonstrated superiority over leuprolide (Lupron) in terms of sustained testosterone (T) suppression through 48 weeks, T recovery following discontinuation, and a 50% reduction in major adverse cardiovascular events (MACE). Leuprolide, a luteinizing hormone-releasing hormone (LHRH) agonist, is administered subcutaneously, as are other androgen deprivation therapy options.

The sustained castration rate with relugolix was 96.7% (95% CI, 94.9%-97.9%) versus 88.8% (95% CI, 84.6%-91.8%) with leuprolide, for a 7.9 percentage point difference between the therapies. T recovery to at least 280 ng/dL at 90 days was 54.0% with relugolix versus 3.0%, and the cumulative incidence of MACE was 2.8% versus 5.6%, respectively.

Gomella said that relugolix will be an important part of discussion at New York GU

 given its recent addition to the treatment paradigm. “The HERO trial demonstrated that relugolix had excellent suppression of testosterone,” Gomella said. “And, as an oral antagonist, it showed a very rapid decline in testosterone in the studies. It’s another brand-new option in prostate cancer. Urologists are going to have to become familiar with this new agent and how to choose the optimum patient for the use of this oral agent for androgen deprivation therapy. While urologists are very comfortable with injectable agents to lower testosterone, this formulation is something that we’re not used to using in daily practice.”

Relugolix also has the advantage of coming in tablet form, as opposed to degarelix (Firmagon), the only other FDA-approved GnRH receptor antagonist, which is administered monthly as a subcutaneous injection in the abdominal region. “Since relugolix is an antagonist, you do not see a surge in testosterone at week 2 that you see with the LHRH agonists,” Gomella said. “So there is some benefit to using an antagonist in certain settings.”

In terms of imaging, the impact of the FDA approval of Ga 68 PSMA-11 in December 2020 will not be widely available in clinical practice but it is a noteworthy development nonetheless, Gomella said. The radioactive diagnostic agent, which is administered as an intravenous injection, is indicated for patients with suspected prostate cancer metastases who are considered potentially curable by surgery or radiation therapy. It also is indicated for patients with suspected recurrence based on rising PSA levels.

As it stands now, Ga 68 PSMA-11 is only approved for use at the University of California (UCLA), Los Angeles and UCLA, San Francisco, where studies have taken place. Outside of a clinical trial at other centers, the California sites are the only locations authorized in the United States for the diagnostic, although Gomella said it has been available for some time in Europe, Australia, and New Zealand.

“PSMA PET scan is designed to pick up metastases from prostate cancer at a very low PSA level, and a very low volume of metastases compared to traditional agents such as MRIs, CAT scans, and bone scans. While other PET agents for prostate cancer are available, PSMA PET imaging is something that’s going to be commonly utilized as it becomes more widely available in the United States,” Gomella said.

In a comparative study (NCT03515577), UCLA investigators evaluated 50 patients with biochemical recurrence after a radical prostatectomy with low PSA levels with the standard 18F-fluciclovine PET-CT scan and the PSMA PET-CT. The PSMA scan detected recurrences of prostate cancer in 56% of scans, compared with 26% with the fluciclovine scan, for an odds ratio of 4.8 (95% CI, 1.6-19.2; 

 “Hopefully, there will be other centers around the United States that will be eligible to jump on their FDA approval,” Gomella said.

A related approach under investigation is the use of PSMA-based theragnostics. This approach combines therapeutic and diagnostic functions in the management of metastatic prostate cancer, Gomella said. One such agent under study is lutetium-177labeled PSMA-617 (LuPSMA), a radionuclide therapy that significantly improved PSA response compared with cabazitaxel (Jevtana) in men with metastatic CRPC whose disease progressed after docetaxel treatment (N = 200) in the phase 2 TheraP study (NCT03392428). The reduction in PSA, defined as 50% or greater from baseline, was 66% (95% CI, 56%-75%) in the LuPSMA arm versus 37% (95% CI, 27%-46%) with cabazitaxel, for an absolute difference of 29% (95% CI, 16%-42%; 

“Using the theragnostics approach, a prostate cancer avid antibody finds the cell, and there’s a radioactive payload that’s associated with it,” Gomella said. “And once that antibody binds to the malignant cell, a radioisotope such as lutetium-177 kills the cancer cells.”

Gomella said there will be several topics on tap at New York GU™ involving advances in bladder cancer. These include treating patients with high-risk, non–muscle invasive bladder cancer (NMIBC) who are not responsive to BCG with pembrolizumab (Keytruda). In January 2020, the FDA approved pembrolizumab monotherapy in this setting for NMIBC with carcinoma in situ with or without papillary tumors.

The approval was based on findings from the KEYNOTE-057 trial (NCT02625961) involving 96 patients who had undergone transurethral resection of bladder tumor (TURBT) to remove all resectable disease. The complete response rate for these patients, defined as negative results for cystoscopy with TURBT or biopsies as applicable, was 41% (95% CI, 31%-51%), with a median duration of response of 16.2 months (range, 0.0-30.4+), with 46% of the responders (n = 18) exhibiting a response for 12 months or longer.

“What was particularly fascinating about this approval is the fact that this is a systemic therapy for non–muscle invasive bladder cancer,” Gomella said. “This is not used as an intravesical agent.”

Emerging therapies generating excitement in NMIBC settings include nadofaragene f iradenovec (also known as rAd-IFNα/ Syn3), an adenovirus vector-based gene therapy that targets urothelial cells, as an alternative to radical cystectomy in BCG-nonresponsive NMIBC.

In a January 2021 publication, Gomella and colleagues reported findings from a phase 3 multicenter trial (NCT02773849), supported by the Society of Urologic Oncology, of nadofaragene firadenovec in BCG-nonresponsive NMIBC. Within 3 months of the first dose, the therapy elicited a complete response in 53.4% of 103 patients (n = 55) with carcinoma in situ with or without concomitant high-grade Ta or T1 disease. Of these patients, 45.5% (n = 25) maintained their response at 12 months.

“Clinical trials showed that this was a very effective intravesical gene therapy for non-muscle invasive bladder cancer. This is another breakthrough development in NMIBC,” Gomella said.

The FDA is currently evaluating a biologics license application for nadofaragene firadenovec, according to FerGene Inc, the company developing the drug.

Another development that experts will discuss at New York GU

 is mitomycin gel (Jelmyto), which was approved in April 2020 for patients with low-grade upper tract urothelial cancer (UTUC) based on data from the single-arm, phase 3 OLYMPUS trial (NCT02793128). Of the 71 patients treated with mitomycin gel, 58% achieved had a complete absence of tumor lesions 3 months after receiving therapy; 19 of the 41 responders maintained a complete response at 12 months (median duration, not reached; range, 0-8.8+ months).

 The therapy has implications in the management of bladder cancer; Gomella said approximately 10% to 15% of patients with bladder cancer can develop UTUC and 20% to 30% of those diagnosed with UTUC may develop bladder cancer.

“At cool temperature, this agent is liquid but when warm it becomes a gel. This is injected into the upper urinary tract through the bladder,” Gomella said. “This agent has allowed us to maintain the renal unit in many patients with low-grade urothelial carcinoma who otherwise may have no option other than taking their kidney out. So this is another novel urothelial/bladder cancer development that we’ve had over the past year.”

Throughout his career, Gomella has emphasized a team spirit in oncology care. One of his most prominent efforts in recent years has been leading the urology effort in the Philadelphia Prostate Cancer Consensus, which brings together experts from throughout the United States and abroad to discuss the role of genetic testing in prostate cancer. In 2017, the consensus meeting produced the first comprehensive set of recommendations to guide physicians on when to offer men genetic consultation. Two years later, they reconvened a 2019 consensus in Philadelphia to consider challenges in the execution and education of prostate cancer germline testing.

The 2017 meeting, which took place just a few years after the growing recognition that some prostate cancers were related to genetic risk, was an important milestone, said Philip W. Kantoff, MD, a 2014 Giants of Cancer Care

 award winner and chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center in New York, New York.

“That was a very important meeting, not as much scientifically as educationally, because a lot of the people who were invited were urologists who are not as familiar with the importance of germline testing,” Kantoff said. “It has really taken off with regard to testing for more aggressive forms of prostate cancers and looking for DNA repair abnormalities that might be significant.”

Genomic testing is one of the most exciting areas of development in Gomella’s eyes. “Identification of these genetic alterations is giving us another alternative pathway to treat these men who ultimately develop metastatic castrate-resistant prostate cancer,” he said.

More than 20 years before the consensus conferences, Gomella was busy launching other collaborative projects. In 1993, he teamed up with a 

 science writer to publish the first book specifically addressing prostate cancer for the public, 

 In the mid-1990s, he introduced a multidisciplinary clinic at the Sidney Kimmel Cancer Center where patients are able to meet with radiation, medical, and urologic surgical specialists during the same visit. Part of the visit includes evaluation for potential clinical trial participation. Most of the men coming through the multidisciplinary clinic have early prostate cancer and are considering the choice of either active surveillance or intervention, usually with radiation or surgery.

“We’re very proud of this multidisciplinary approach,” Gomella said. “We’ve been doing this approach at the Sidney Kimmel Cancer Center since way back in 1996. We’ve found it to be an amazing experience. We don’t know of any other center that’s been doing it as long as we have. Many other centers have started to do it because it’s a very patient- and family- friendly approach to prostate cancer. We’re all at the same place at the same time to talk to the patient and their family, and then give them our best recommendation for the treatment pathway they should start on.”

In 2014, the multidisciplinary clinic began incorporating an introduction to prostate cancer genetic testing, another first in the f ield. Patients and their families receive an overview of whether pursuing genetic testing is something they should consider after their initial treatment has begun, Gomella said. The goal is to identify patients who have a genetic predisposition not just to prostate cancer but other related inherited malignancies. This includes breast and ovarian cancer in female relatives as well as pancreatic cancer, melanoma, or male breast cancer in the patient or his close family members.

“Testing family members of a patient with prostate cancer is a concept known as cascade testing,” Gomella said. “Is this something that perhaps their children should be aware of, that they might have an inherited genetic predisposition to these related groups of cancer? This requires a very up-close-and-personal discussion with the patient or family. While most patients with prostate cancer do not appear to harbor an inherited genetic risk, 15% to 20% of men may benefit from further genetic evaluation. We believe thoughtful genetic testing and counseling is the future of precision medicine in all of cancer care.”

Another point of pride is the scientific research that Gomella and colleagues have conducted into molecular biomarkers. “When it comes to a basic science discovery, something that usually does not get a lot of attention is something that I’m particularly proud of. In 1992, we described the first molecular test to identify circulating prostate cancer cells in the blood. I think this really laid the groundwork for others who started to investigate whether we can use molecular tests to identify circulating tumor cells and other molecular targets in the blood.”

The research was ahead of its time, he said. “Over the past 25 years, the basic molecular work we did has been eclipsed and expanded dramatically. It was probably too early; we and others who joined in this preliminary prostate cancer work didn’t really fully understand the biology of molecular blood testing.”

Although Gomella has been a driving force in urologic oncology for many years, his early career path was winding and unpredictable. In high school, he figured he would go into engineering, psychology, or medicine. But while attending Queens College at the City University of New York, he became involved in emergency medical services. He ended up founding a volunteer ambulance unit in New York City and decided to focus on emergency medicine. Part of his focus evolved into teaching cardiopulmonary resuscitation (CPR) techniques to medical students. “It’s hard to believe today, but when I was a medical student in the late 1970s, medical students were not routinely learning CPR,” he said.

“Then I had a revelation as a third-year medical student. When you’re in emergency medicine, you spend a lot of time calling trauma surgeons to come to the emergency [department] and care for patients,” Gomella said. “Seeing these trauma surgeons in action f irst hand greatly impressed me. That is when I decided I wanted to be a surgeon.”

After 2 years of general surgery, he migrated to urology. He joked that he made the move because he discovered that a doctor is more likely to remain married after a urology residency than a general surgery residency. But in actuality, he was recruited by the chief of urology, J. William McRoberts, MD, at his training site, the University of Kentucky College of Medicine, who made him realize a urology residency could point him toward research and a career in academic medicine.

Gomella completed a fellowship in surgical oncology in the surgery branch at the National Cancer Institute, where he worked with 2013 Giants of Cancer Care

 award winner Steven A. Rosenberg, MD, PhD, and urologic oncologist W. Marston Linehan, MD. In 1988, he was recruited by former dean Joseph Gonnella, MD, to help start a new cancer center at Jefferson and has been there ever since.

“The grass is always greener someplace else, but Jefferson and the Sidney Kimmel Cancer Center have been a great place for me. Many of my colleagues who got their start here have gone on to greatness elsewhere, but there are also a lot of my colleagues who are still here fighting the good fight with us,” Gomella said.

Beaver JA, Kleutz PG, Pazdur R. Metastasis-free survival - a new end point in prostate cancer trials. N Engl J Med. 2018;378(26):2458-2460. doi:10.1056/NEJMp1805966

Hematology/oncology (cancer) approvals & safety notifications. FDA. Updated January 22, 2021. Accessed January 31, 2021. https://bit.ly/39AwUT5

Moreno JG, Croce CM, Rischer R, et al. Detection of hematogenous micrometastasis in patients with prostate cancer. Cancer Res. 1992;52(21):6110-6112.

Giri VN, Knudsen KE, Kelly WK, et al. Role of genetic testing for inherited prostate cancer risk: Philadelphia Prostate Cancer Consensus Conference 2017. J Clin Oncol. 2018;36(4):414-424. doi:10.1200/JCO.2017.74.1173

FDA grants accelerated approval to rucaparib for BRCA-mutated metastatic castration-resistant prostate cancer. FDA. Updated May 15, 2020. Accessed January 31, 2021. https://bit.ly/3apoWuS

FDA approves olaparib for HRR gene-mutated metastatic castration-resistant prostate cancer. FDA. Updated May 20, 2020. Accessed January 31, 2021. https://bit.ly/3pCDM7Y

NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 3.2020. Accessed January 31, 2021. https://www. nccn.org/professionals/physician_gls/pdf/prostate.pdf

Premarket approval (PMA) FoundationOne Liquid CDx. FDA. November 6, 2020. Accessed January 31, 2021. https://bit.ly/3an7K9C

FDA approves first oral hormone therapy for treating advanced prostate cancer. News release. FDA. December 18, 2020. Accessed January 19, 2021. http://bit.ly/2Ws5nvz

Shore ND, Saad F, Cookson MS, et al; HERO Study Investigators. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med. 2020;382(23):2187-2196. doi:10.1056/NEJMoa2004325

Multi-discipline review. Center for Drug Evaluation and Research. FDA. December 18, 2020. Accessed January 31, 2021. https://bit.ly/393bDkn

FDA approves first PSMA-targeted PET imaging drug for men with prostate cancer. News release. FDA. December 1, 2020. Accessed December 1, 2020. https://bit.ly/3ajr0Vm

Calais J, Ceci F, Eiber M, et al. 18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncol. 2019;20(9):1286-1294. doi:10.1016/S1470-2045(19)30415-2

Hofman MS, Emmett L, Sandhu SK, et al. TheraP: a randomized phase III trial of 177Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel: initial results (ANZUP protocol 1603). J Clin Oncol. 2020;38(suppl 15):5500. doi:10.1200/JCO.2020.38.15_suppl.5500

FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer. FDA. Updated January 8, 2020. Accessed January 22, 2021. https://bit.ly/2NX5MW1

Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021;22(1):107-117. doi:10.1016/S1470-2045(20)30540-4

FDA approves mitomycin for low-grade upper tract urothelial cancer. FDA. Updated April 15, 2020. Accessed January 31, 2021. https://bit.ly/2L5D5F4

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Gomella LG, Fried JJ. Recovering from Prostate Cancer. HarperCollins; 1993.

A recent wave of drug approvals for treating prostate cancer in earlier disease states, coupled with genomic advances, may help pave the way for a shift toward handling the malignancy as a chronic condition. 

Gomella Lauds Breakthroughs  in GU Cancers


Denise Myshko is your editorial contact for the Oncology Business Management section of 

, as well as the corporate newsletters. She joined 

 in March 2020. Before that, she was managing editor of PharmaVOICE, a trade publication in the pharmaceutical industry. Email: 

Excitement took wing in the scientific community in the early 1990s, when the first gene therapy trial showed significant success, only to crash at the end of the decade with a patient’s tragic death. 

Twenty years later, the excitement is back and greater than before. Although safety remains a concern, investigators are breaking ground in cell and gene therapy, and many believe that ultimately, a string of cured cancers will follow.

In 2017, the excitement over these therapies returned in spades when the FDA signed off on a cell-therapy drug for the first time, approving the chimeric antigen receptor (CAR) T-cell treatment tisagenlecleucel (Kymriah; Novartis) for patients with B-cell precursor acute lymphoblastic leukemia. At last, scientists had devised a way to reprogram a person’s own T cells to attack tumor cells.

“We’re entering a new frontier,” said Scott Gottlieb, MD, then-FDA commissioner, in announcing the groundbreaking approval. 

Gottlieb was not exaggerating. The growth in CAR T-cell research is exploding. Although only a handful of cell and gene therapies are on the market, the FDA predicted in 2019 that it will receive more than 200 investigational new drug applications per year for cell and gene therapies, and that by 2025, it expects to have accelerated to 10 to 20 cell and gene therapy approvals per year.

“We can absolutely cut the number of cancer deaths down so that one day in our lifetimes it can be a rare thing for people to die of cancer,” said Patrick Hwu, MD, president and CEO of Moffitt Cancer Center in Florida and among gene therapy’s pioneers. “It still may happen here and there, but it’ll be kind of like people dying of pneumonia. It’s like, ‘He died of pneumonia? That’s kind of weird.’ I think cancer can be the same way.”

“Essentially, you can kill any cancer cell that has an antigen that is recognized by the immune cell,” Hwu said. “The key to curing every single cancer, which is our goal, is to have receptors that can recognize the tumor but don’t recognize the normal cells.”

Implications for the Community Oncologist

Community oncologists will need to be increasingly familiar about the various products, including their immediate and longer-term risks, Bo Wang, MD, and Deepu Madduri, MD, recently wrote in 

 “It is key to understand the optimal time for referring these patients to an academic institution, as well as how to manage the requisite post CAR T-cell therapy in the community setting.” Madduri is an assistant professor of medicine, hematology and medical oncology, as well as associate director of cellular therapy service, and director of clinical operations with the Center of Excellence for Multiple Myeloma at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai in New York, New York. Wang is a third-year clinical fellow in hematology/oncology at Mount Sinai.

Early referral to academic centers and hospitals equipped to deliver therapies is crucial for patients eligible for therapy. However, as advances continue in the field, community practices may be called upon to administer therapies in their clinic.

The Community Oncology Alliance (COA) envisions a broader role for the settings in which CAR T-cell therapies can be administered. When the Centers for Medicare & Medicaid Services (CMS) was considering coverage for CAR T-cell therapies in 2019, COA officials argued against limiting approvals to hospitals.

“It is important to understand that there are state-of-the-art community oncology practices that have significant experience and capabilities in administering highly complex treatments,” COA officials wrote in a letter to CMS. “For example, stem cell transplants, which are similar in complexity to CAR T therapy, are performed successfully in the community oncology practice setting.”

Broader use of gene therapies depends on several factors, including navigating the logistics of gene therapies, addressing the high costs, and managing toxicities.

Autologous CAR T-cell therapies involve a manufacturing process that requires coordination between the treating facility and the processing facility. Following leukapheresis, patients may require maintenance therapy to control disease progression during the manufacturing time, which can take 3 to 5 weeks.

In terms of cost, gene and cell therapies can cost from $375,000 to $475,000 per dose and they may face coverage restrictions from payers. Approvals could take weeks to obtain.

Because of cytokine release syndrome and neurotoxicities associated with CAR T-cell therapy, the FDA mandates risk evaluation and mitigation strategy training for centers. 

Further, providers may find that real-world experiences with gene therapies are different from those seen in the clinical trial setting, according to Ankit J. Kansagra, MD.

In a presentation at the 2020 American Society of Clinical Oncology Virtual Education Program, Kansagra, an assistant professor of medicine and Eugene P. Frenkel, MD, Scholar in Clinical Medicine at Harold C. Simmons Comprehensive Cancer Center in Dallas, Texas, said that in practice patients may be older and have more aggressive disease, with double- and triple-hit lymphomas.

Specifically, Kansagra noted that medications such as steroids and/or tocilizumab (Actemra) to prevent or treat cytokine release syndrome or other toxicities were more frequently used in the real-world setting than what had been seen in clinical trials.

Although safety remains a concern with gene therapy, investigators are breaking ground in cell and gene therapy, and many believe that ultimately, a string of cured cancers will follow.

Larry Hanover

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