Nearly 20% of patients participating in middle-stage cancer drug trials may receive treatments that eventually receive U.S. Food and Drug Administration (FDA) approval, according to a recent study published by Ouimet et al in the Journal of the National Cancer Institute. The findings may have significant implications for drug development and clinical trial recruitment.
Background
In phase I trials, researchers assess the drugs for safety and dosing, and phase II clinical trials determine whether a new drug shows signs of efficacy. Drugs showing potential in phase II trials are then evaluated in phase III trials, which are conducted at multiple centers with at least several hundred patients and often inform whether the FDA approves the drug for use.
However, unlike initial phase I trials, all patients participating in phase II trials receive drugs at the doses intended for routine use, with the expectation that the drugs will be active and beneficial. With more patients treated at an active dose, the drugs are more likely to have side effects. Therefore, the question of efficacy in phase II trials is a critical consideration in patients who desire to receive newer treatments.
Study Methods and Results
In this study, investigators identified 2,730 phase II clinical trials beginning between November 2012 and November 2015—1,154 of which met eligibility and 400 of which were randomly sampled for inclusion—encompassing 25,002 patient-participants in 608 specific cohorts, including control arms. The trials tested 332 drugs, 25 of which were evaluated in more than 10 trials, 155 of which were evaluated in 2 to 10 trials, and 152 of which were evaluated in 1 trial. The goal of the study was to estimate the proportion of patients with cancer who participated in phase II trials and received new interventions that were later deemed safe and effective as well as approved by the FDA.
The investigators found that the FDA later approved 71 drug regimens in the tested indication, and 16% of the patients in phase II trials received such regimens. Nonetheless, they indicated that receipt of a drug that later received FDA approval did not always demonstrate benefit in the patients with cancer.
“Keep in mind that approved drugs don’t work for every [patient]. For many FDA-approved cancer drugs, only half to a tenth of patients meaningfully benefit,” suggested lead study author Charlotte Ouimet, MSc, of the McGill University School of Population and Global Health in Montreal.
Conclusions
The findings may help inform patients about expectations for phase II trials. Although most of the patients who enroll in these trials have advanced cancers and lack standard treatment options, many of them may regard a 16% probability of receiving a drug that later secures FDA approval for their condition as favorable.
“If you’re a patient [with cancer] and you are invited into a phase II trial, keep in mind that five of six patients get treatments that do not go on to approval,” emphasized senior study author Jonathan Kimmelman, PhD, of the McGill University School of Population and Global Health. “Just the same, your odds are dramatically better than they would be for a phase I trial. Your odds of receiving an effective drug in phase II are quite a bit higher than for phase I trials, [b]ut probably still a lot lower than for phase III trials—where the odds are probably more like one in three,” he concluded.
Disclosure: For full disclosures of the study authors, visit academic.oup.com.
