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# FDA Reviewers Question Keytruda Breast Cancer Study
- URL: https://www.fdaweb.com/fda-reviewers-question-keytruda-breast-cancer-study/
- Published: 2021-02-05T12:00:00.000Z
- Updated: 2026-09-14T16:45:39.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5148605

FDA reviewers are taking issue with a Merck study supporting a new indication for Keytruda (pembrolizumab) for treating patients with high-risk early-stage triple-negative breast cancer (TNBC), in combination with chemotherapy as neoadjuvant treatment, then as a single agent as adjuvant treatment after surgery. FDA [briefing documents](https://www.fda.gov/media/145654/download?ref=fdaweb.com) released in advance of a 2/9 Oncologic Drugs Advisory Committee meeting show agency reviewers hitting at the company’s data interpretations from KEYNOTE-522, a randomized, placebo-controlled trial involving 1,174 patients with high-risk, early-stage TNBC. The co-primary endpoints were pathologic complete response (pCR) rate and event-free survival (EFS), and overall survival (OS) was a key secondary endpoint.

The committee is scheduled to discuss reviewer-indentified issues such as event-free survival data being immature, the improvement in pCR rate is small, and the addition of pembrolizumab to neoadjuvant and adjuvant treatment “adds toxicity which may be severe, irreversible, or require lifelong medication,” according to the briefing documents. “FDA does not agree that the small pCR rate difference between treatment arms is clinically meaningful,” they say. “As KEYNOTE-522 is a randomized study with an add-on design, the FDA interprets the pCR rate on the pembrolizumab arm in context of the pCR rate on the control arm. Interim analyses may overestimate the treatment effect, particularly when the number of events is small. The data are not sufficiently mature for FDA to consider these interim EFS results as a reliable estimate of the EFS treatment effect.”

The reviewers say they believe that there is “uncertainty” whether Keytruda will be associated with long-term clinical outcomes of EFS and OS in the indicated population. “The FDA has repeatedly expressed concerns about the KEYNOTE-522 trial design and results to the applicant and discouraged submission of this marketing application,” the briefing document says. In a meeting with Merck in 2016, FDA said it dismissed a proposed target of 15% improvement in pCR rate, saying it may not be adequate to predict improvement in long-term outcomes in patients with early-stage TNBC.

With so much uncertainty, FDA says it decided to convene the committee meeting to discuss and vote on the following question: “Should a regulatory decision on pembrolizumab in combination with multi-agent chemotherapy for neoadjuvant treatment followed by pembrolizumab monotherapy for adjuvant treatment of high-risk early-stage TNBC be deferred until further data are available from future analyses?”