It’s no revelation that patients in clinical trials are different from real-world patient populations, Dr Lara noted. “That is common sense, because patients on clinical trials are younger and need to be in better shape.”
“The question of whether findings are immediately applicable to the broad population has to lie in the physician/patient encounter,” he said. “The physician needs to make a clinical decision; you take the available evidence and weigh that and apply it to the patient in front of you. Not just in oncology—but in medicine, the patient in front of you isn’t an exact copy of the patient in the clinical trial.”
While Dr Mailankody and Dr Prasad see the example of sorafenib in hepatocellular carcinoma as “emblematic” of a more widespread problem with cancer drug outcomes, it’s possible that these types of cases could be detected without overhauling the existing FDA regulatory approach to drug approvals.
“Cherry-picking compounds and then saying most drugs don’t have survival benefits is a little misguided,” said Donald Harvey, PharmD, BCOP, FCCP, FHOPA, associate professor of hematology/medical oncology and pharmacology at Emory University’s School of Medicine, and director of the Winship Cancer Institute’s Phase I Clinical Trials section in Atlanta, Georgia. “I think they’re overreaching.”
“Erlotinib for pancreatic cancer,” Dr Harvey said, “was pretty marginal, but in the example of patients with lung cancer and EGFR mutations, they certainly have meaningful benefit from erlotinib and other approved EGFR-targeted therapies.”
Dr Harvey also disagrees that real-world overall survival is the only gold standard for assessing cancer drugs. “We all want to see patients with cancer live longer lives, but progression-free survival is still an important endpoint when it comes with a good quality of life, which many targeted drugs have provided.”
Dr Harvey agrees that there is “a lot of work to do” to better harmonize clinical trial and actual patient populations, but there are efforts already underway to do that.
The American Society of Clinical Oncology (ASCO) and Friends of Cancer Research are leading efforts to “modernize” cancer trial eligibility, he said. Age is an issue, but “the bigger variable” is performance status.
“Many trials mandate a performance status of 0 or 1 by the ECOG scale and that excludes a significant number of the patients who will be treated post-marketing [after FDA approval], who have a performance status of 2 or sometimes even 3,” he said.
The proposal to delay final FDA approval until real world overall survival data are available is an interesting proposal but “would be incredibly challenging to put into place,” Dr Harvey said. That’s because enrolling patients on post-marketing trials requires additional time requirements that patients and oncologists are likely to want to sidestep to hasten the initiation of care.
“We’re still at a point where only 3% of all adult patients enter cancer trials overall,” Dr Harvey noted. “There are still challenges across the board.“
- Mailankody S, Prasad V. Overall survival in cancer drug trials as a new surrogate end point for overall survival in the real world. JAMA Oncol. 2016 Nov 17. doi: 10.1001/jamaoncol.2016.5296 [Epub ahead of print]
- Fojo T, Mailankody S, Lo A. Unintended consequences of expensive cancer therapeutics—the pursuit of marginal indications and a me-too mentality that stifles innovation and creativity. JAMA Otolaryngol Head Neck Surg. 2014;140(12):1225-36. doi: 10.1001/jamaoto.2014.1570