1. Eastman, Peggy

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In an ongoing effort to expand restrictive eligibility rules and make cancer clinical trials more representative of the general population, the American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FOCR) held a webinar to share new recommendations designed to increase trial inclusiveness.

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ASCO President Lori J. Pierce, MD, FASTRO, FASCO, noted that ASCO has been collaborating on the project to expand trial eligibility for 5 years. She said it is important to achieve greater representation and inclusion of underrepresented groups in cancer clinical trials. "Equity for every patient every day everywhere," her theme as ASCO president, goes along with the effort to expand trial eligibility, said Pierce, a radiation oncologist who is Professor and Vice Provost for Academic and Faculty Affairs at the University of Michigan, as well as Director of the Michigan Radiation Oncology Quality Consortium.


In 2017, the FOCR released its first paper on less restrictive clinical trial eligibility rules, and "we're already seeing this work helping patients," said FOCR founder and Chair Ellen Sigal, PhD. She, like Pierce, emphasized that cancer clinical research needs to be equitable and representative of the total population receiving therapy.


In a joint research statement published in the journal Clinical Cancer Research (2021; doi: 10.1158/1078-0432.CCR-20-3852), multi-stakeholder working groups convened by ASCO and the FOCR made new recommendations to modernize eligibility criteria. The recommendations cover washout periods for prior treatments and interventions, concomitant medications, prior therapies, laboratory reference ranges and test intervals, and performance status.


For example, the recommendations state that concomitant medication use should only exclude patients from trial participation when clinically relevant drug-drug interactions or potential overlapping toxicities will impact safety or efficacy. Similarly, the statement says that tailoring the use of laboratory test requirements and testing intervals may increase the number and diversity of patients in clinical trials and provide clinical data that more closely represent the general population. The statement also says that clinical trial sponsors and regulators should re-examine the use of prior therapy exposure as a restrictive selection criterion in order to maximize clinical trial participation.


"Implementation of the recommendations is intended to result in greater ease of determining patient eligibility," noted the research statement. "Increased opportunities for patient participation in research will help address longstanding underrepresentation of certain groups and produce evidence that is more informative for a broader patient population." In addition, "more patients eligible will also likely speed clinical trial accrual." In 2017, the ASCO/FOCR joint project developed and published consensus recommendations related to broadening cancer clinical trial eligibility in four areas that are frequently exclusionary: brain metastases, HIV/AIDS, organ dysfunction, and minimum age for enrollment.


This project "is something close to my heart," said Edward S. Kim, MD, MBA, Physician-in-Chief at the City of Hope and lead author on the new joint research statement published in Clinical Cancer Research. He noted that "all these eligibility criteria really add up," and researchers are trying to adjust, pivot, and modernize trial eligibility so that the trial population resembles the population intended for the therapy being studied.


Following the destructive effects of the COVID-19 pandemic on clinical cancer research, "we really need to get back to accrual," said Ned Sharpless, MD, Director of the National Cancer Institute (NCI). When cancer clinical trial enrollment rules are too restrictive, "it's bad for everybody; it's bad for patients, it's bad for progress," said Sharpless.


Early in the pandemic, he warned about the expected harmful effects of the pandemic on clinical cancer research. As previously reported by Oncology Times, NCI and the National Institute of Biomedical Imaging and Bioengineering awarded seven contracts to develop digital health solutions, such as smartphone apps, wearable devices, and software that could help address the COVID-19 pandemic. In addition, NCI, along with FDA, provided guidance for clinical trial activities affected by the pandemic.


Acting FDA Commissioner Janet Woodcock, MD, agreed with Sharpless on the need to get back to a more normal clinical research environment post-pandemic. She noted that in November of 2020 the FDA released a guidance document on enrolling underrepresented patients in clinical trials. Woodcock and Sharpless both stressed the importance of using real-world evidence in clinical trials to gain new knowledge that will be potentially valuable in clinical practice.


NSCLC Trial Eligibility

During the webinar, R. Donald Harvey, PharmD, Medical Director of the Clinical Trials Office of Emory University's Winship Cancer Institute, discussed a real-world analysis of applying select ASCO/FOCR recommendations on broadening trial eligibility for patients with advanced non-small cell lung cancer (NSCLC). This retrospective, observational analysis was published in the journal Clinical Cancer Research along with the joint statement on new trial eligibility recommendations. Harvey, who was a co-author of the joint research statement, was the lead author of this second paper and Kim was a co-author.


The NSCLC analysis of 10,500 patients from ASCO's CancerLinQ Discovery database showed that broadened eligibility criteria (including brain metastases, other malignancies, and renal function) has the potential to nearly double the number of trial participants and include those who are more representative of patients encountered in clinical practice.


Specifically, broadened criteria would allow 10,346 (98%) to be potential trial participants. Using traditional, restrictive criteria, however, would have excluded 5,005 (48%) of the patients from trial participation. In this analysis, most patients had stage IV disease, the median age was 68 and 73 percent were White. The analysis, Harvey said, showed that, in using broadened trial enrollment criteria, the numbers of eligible women, patients aged 75 or older, and those with stage IV cancer were considerably greater than using traditional, more restrictive enrollment criteria. Harvey said narrower criteria that exclude potential trial participants should be used only for a compelling scientific rationale.


"I'm optimistic that these recommendations will be well-received," said Raymond P. Perez, MD, a medical oncologist who is Program Leader for Early Clinical Development in Oncology at Bristol Myers Squibb and a co-author of the joint new research statement. He said bringing all stakeholders to the table will help drive adoption of expanded clinical trial eligibility criteria.


"This feels very personal to the individual patient," said patient advocate and breast cancer survivor Patricia A. "Patty" Spears, a co-author of the joint research statement. "Patients have been waiting for this." Spears noted that "it's not a great feeling" when a cancer patient is told that he or she does not qualify for a clinical trial. She said it is time to change the dogma on homogeneous trial populations, because "it is not real life." Spears added of the new ASCO/FOCR joint research statement, "I think these recommendations give a great roadmap."


Peggy Eastman is a contributing writer.