Although clinical trials to date have “improved the lives of countless patients with cancer, the work has been slow, costly, and empiric,” Lee M. Ellis, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, and colleagues wrote in an American Society of Clinical Oncology (ASCO) Special Article published in the Journal of Clinical Oncology.

Using targeted therapies “selected by reliable and biologically relevant biomarkers have produced substantial improvements in outcomes that have rapidly transformed patient care for several cancer types,” they added. These advances should allow clinical trials to be implemented “where meaningful advances in patient outcomes can be achieved with smaller numbers of trial participants (ie, smaller and smarter trials).”

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To address the design of future clinical trials resulting in significantly improved survival, quality of life, or both, the ASCO Cancer Research Committee convened four working groups, focusing on carcinomas of the pancreas (led by Emile Voest, MD, PhD, University Medical Center Utrecht, the Netherlands), breast (Lowell E. Schnipper, MD, Beth Israel Deaconess Medical Center, New York, NY), lung (Roy Herbst, MD, PhD, Yale Cancer Center, New Haven, CT), and colon (Alan P. Venook, MD, Helen Diller Family Comprehensive Cancer Center at University of California San Francisco). Each group was tasked to select a patient population and primary and secondary endpoints for potential trials. The working groups comprised clinical investigators, patient advocates, biostatisticians, and oncologists from the US Food and Drug Administration and from industry.1

The population and primary endpoint—improvement over current overall survival (OS) that would be clinically meaningful—for randomized, phase 3 clinical trials the working groups identified include:

  • Pancreatic cancer: FOLFIRINOX-eligible patients, 4 to 5 months (current baseline median OS, 10 to 11 months); and gemcitabine or gemcitabine/nab-paclitaxel–eligible patients, 3 to 4 months (current baseline median OS, 8 to 9 months)
  • Breast cancer: metastatic triple-negative, previously untreated for metastatic disease, 4.5 to 6 months (current baseline median OS, 18 months)
  • Lung cancer: nonsquamous cell carcinoma, 3.25 to 4 months (current baseline median OS, 13 months) and squamous cell carcinoma, 2.5 to 3 months (current baseline median OS, 10 months)
  • Colon cancer: disease progression with all prior therapies (or not a candidate for standard second- or third-line options), 3 to 5 months (current baseline median OS, 4 to 6 months)

Secondary endpoints for all trials include improvement in 1-year survival rate (%) and improvement in progression-free survival (months).

“This project undertaken by four groups of experts to define clinically meaningful outcomes for cancer clinical trials provides an example of the deliberations that we believe clinical trial sponsors and investigators should undertake in developing new therapies for patients with advanced cancer,” Ellis et al wrote. “We are calling on the community of patients, patient advocates, and clinical investigators to collectively raise the bar in our expectations of the benefits of new therapies. The benchmarks we propose highlight the promise of predictive biomarkers and their associated targeted therapeutics to achieve these goals.”

This includes establishing comprehensive biospecimen banks for each trial so that investigators can determine which patients are most likely to benefit from treatment as well as discover and validate biomarkers. “In our recommendations, we also address the importance of quality-of-life and toxicity issues,” Dr. Ellis said. “If a patient experiences more toxicity than with current therapies, the therapy should provide a greater benefit.”