Do Patients Benefit from Cancer Trial Participation?


Overall, patients with solid tumors who receive an investigational cancer drug experience small progression-free survival (PFS) and overall survival benefits but much higher toxicity than those who receive a control intervention.


  • The view that patients with cancer benefit from access to investigational drugs in the clinical trial setting is widely held but does necessarily align with trial findings, which often show limited evidence of a clinical benefit. First, most investigational treatments assessed in clinical trials fail to gain regulatory approval, and the minority that are approved tend to offer minimal clinical benefit, experts explained.
  • To estimate the survival benefit and toxicities associated with receiving experimental treatments, researchers conducted a meta-analysis of 128 trials comprising 141 comparisons of an investigational drug and a control treatment, which included immunotherapies and targeted therapies.
  • The analysis included 42 trials in non–small cell lung cancer (NSCLC), 37 in breast cancer, 15 in hepatobiliary cancer, 13 in pancreatic cancer, 12 in colorectal cancer, and 10 in prostate cancer, involving a total of 47,050 patients.
  • The primary outcome was PFS and secondary outcomes were overall survival and grades 3-5 serious adverse events.


  • Overall, the experimental treatment was associated with a 20% improvement in PFS (pooled hazard ratio [HR], 0.80), corresponding to a median 1.25-month PFS advantage. The PFS benefit was seen across all cancer types, except pancreatic cancer.
  • Overall survival improved by 8% with experimental agents (HR, 0.92), corresponding to 1.18 additional months. A significant overall survival benefit was seen across NSCLC, breast cancer, and hepatobiliary cancer trials but not pancreatic, prostate, colorectal cancer trials.
  • Patients in the experimental intervention group, however, experienced much higher risk for grade 3-5 serious adverse events (risk ratio [RR], 1.27), corresponding to 7.40% increase in absolute risk. The greater risk for serious adverse events was significant for all indications except prostate cancer (RR, 1.13; 95% CI, 0.91-1.40).


“We believe our findings are best interpreted as suggesting that access to experimental interventions that have not yet received full FDA approval is associated with a marginal but nonzero clinical benefit,” the authors wrote. 

“Although our findings seem to reflect poorly on trials as a vehicle for extending survival for participants, they have reassuring implications for clinical investigators, policymakers, and institutional review boards,” the researchers said, explaining that this “scenario allows clinical trials to continue to pursue promising new treatments — supporting incremental advances that sum to large gains over extended periods of research — without disadvantaging patients in comparator groups.”


Renata Iskander, MSc, of McGill University, Montreal, Quebec, Canada, led this work, which was published online on April 29, 2024, in Annals of Internal Medicine.


There was high heterogeneity across studies due to variations in drugs tested, comparators used, and populations involved. The use of comparators below standard care could have inflated survival benefits. Additionally, data collected from might be biased due to some trials not being reported. 


Canadian Institutes of Health Research supported this work. The authors received grants for this work from McGill’s University, Rossy Cancer Network, and National Science Foundation. One author received consulting fees outside this work. The other authors declared no competing interests.

Source link

error: Content is protected !!