In late 2017, the US Food and Drug Administration (FDA) approved adjuvant sunitinib for patients with renal cell carcinoma (RCC) at high risk of recurrence post-nephrectomy.1 The approval is, however, controversial among some physicians, who argue that the overall survival (OS) and disease-free survival (DFS) data do not justify the FDA’s decision.
Bishal Gyawali, MD, PhD, is a medical oncologist from Nepal with experience in cancer care in both low- and high-income countries. He obtained his PhD from Japan as a MEXT scholar and is now working as a research fellow at Brigham and Women’s Hospital at Harvard Medical School in Cambridge, Massachusetts.
Cancer Therapy Advisor asked Dr Gyawali, who coauthored a viewpoint just published in JAMA Oncology, to discuss the FDA’s approval of sunitinib, and whether it is an example of what he calls “regulatory capture” in medicine.2
Cancer Therapy Advisor (CTA): What is regulatory capture, and how is the FDA’s approval of adjuvant sunitinib an example of it?
Dr Gyawali: In any policy decision, there are some stakeholders with high-stake interest. Other stakeholders who don’t share these interests are less energized about the outcome of these decisions, while high-stake interest stakeholders are actively energized to have a decision in favor of their interest. Regulatory policy decisions can be influenced in this way, which is called regulatory capture.
In the case of adjuvant sunitinib in RCC, high-stake interest groups tried to influence the policy decision by highlighting the DFS benefit and burying OS curves in a supplementary appendix.
People with low-stake interest, however, didn’t bother to dig through the data, search for data from another ASSURE trial, or look at the meta-analysis. The FDA decision to grant approval could, therefore, be a case of regulatory capture as the industry influenced the regulatory agency charged with regulating the industry in question.
CTA: Could you, in brief, describe the data that led to the approval of sunitinib for RCC in the adjuvant setting?
Dr Gyawali: There are 2 important trials that tested sunitinib for RCC in the adjuvant setting: the ASSURE and S-TRAC trials (ClinicalTrials.gov Identifiers: NCT00326898 and NCT00375674, respectively).
OS was not improved in both. DFS was also not improved in ASSURE but improved in S-TRAC; I previously did a meta-analysis of these 2 trials, which showed that adjuvant sunitinib actually doesn’t improve DFS or OS but increases the risks of grade 3 or higher adverse effects.3
The FDA, however, clearly gave more importance to the S-TRAC trial and approved sunitinib on the basis of positive DFS in that trial.
As our viewpoint discusses, it seems some of the ODAC [Oncology Drug Advisory Committee] members were also not aware that OS in the S-TRAC trial was actually negative, as the OS curves in the primary publication of S-TRAC trial were buried in the supplementary appendix.