The FDA has released a draft guidance for makers of breast cancer drugs explaining how to design clinical trials using pathologic complete response (pCR) as a surrogate endpoint to demonstrate the study drug’s efficacy.
Specifically, the guidance discusses the use of pCR to support approval of drugs for neoadjuvant treatment of early-stage breast cancer through the agency’s accelerated approval pathway.
“Despite advances in systemic therapy of early-stage breast cancer over the past few decades, there remains a significant unmet medical need for certain high-risk or poor prognosis populations of early-stage breast cancer patients,” the FDA wrote in its guidance, posted Tuesday. “This guidance is intended to encourage industry innovation and expedite the development of breakthrough therapies to treat high-risk early-stage breast cancer.”
Neoadjuvant chemotherapy, which used to be reserved for patients with locally advanced breast cancer, has become increasingly common for patients with early-stage breast cancer. Giving chemotherapy preoperatively can allow for breast conservation in some patients who would otherwise require mastectomy, and it can allow the oncologist to evaluate tumor response and either stop a therapy that isn’t working or substitute an alternative therapy.
Randomized neoadjuvant trials comparing the same treatment administered preoperatively and postoperatively have suggested that pCR may predict disease-free survival or overall survival in patients with early-stage breast cancer, the guidance said.
The FDA said that “preoperative systemic therapy appears to be an acceptable alternative to standard postoperative systemic therapy of early-stage breast cancer, and facilitating development of new drugs for use in the neoadjuvant setting is a worthwhile objective.”
To date, there has been no definition of pCR for breast cancer, with some investigators defining it as absence of both in situ and invasive cancer following neoadjuvant chemotherapy while others have considered only the invasive component in the definition.
Adopting a single term would make it easier to determine whether a proposed trial design will support accelerated approval, the FDA said, and proposed defining pCR as “the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy.”
Companies that earn approval on the basis of a trial that relied on pCR would be required to perform a post-approval confirmatory trial showing their drugs really do improve disease-free survival or overall survival, the guidance said.
The guidance is open for comment through the end of July.
The FDA will use the comments it receives on the guidance, as well as information from a large meta-analysis, to study the relationship between pCR and disease-free and overall survival and to inform its final position on using pCR appropriately as an endpoint for drug approval.Add Your Knowledge ™
Emily P. Walker, MedPage Today Washington Correspondent, covers Congress, FDA, other health agencies in Washington. She also covers an array of healthcare events in the nation’s capital, focusing on intersection of policy and medicine. After earning a BA in journalism and political science at Western Michigan University, she worked at the Kalamazoo Gazette, Congressional Quartely, and wrote for several medical newsletters.