At an FDA Oncologic Drugs Advisory Committee meeting this week, the panel voted unanimously to defer the recommendation for accelerated approval of pembrolizumab to treat patients with early triple negative breast cancer. 

The 10-member panel reviewed data submitted by the manufacturer from the KEYNOTE-522 clinical trial. 

They found that the interim analysis did not support accelerated approval for pembrolizumab in high-risk, early-stage TNBC with chemotherapy after surgery. 

The approval delay will stand “until further data are available from future analyses of KEYNOTE-522,” according to the FDA’s ODAC Briefing Document. 

“While FDA believes there is an unmet medical need in patients with high-risk, early-stage TNBC for new therapies that result in improved long-term outcomes and survival, it is not clear that the current results are reasonably likely to predict such a benefit,” The FDA wrote in the ODAC Briefing Document. 

KEYNOTE 522 investigated neoadjuvant pembrolizumab plus chemotherapy followed by pembrolizumab monotherapy compared to neoadjuvant chemotherapy plus adjuvant placebo, according to the manufacturer. 

The study’s primary endpoints were “a pathological complete response (pCR) at the time of definitive surgery and event-free survival (EFS),” according to the manufacturer. 

The FDA’s ODAC panel took issue with the interpretation of KEYNOTE-522’s improvement in pCR as an indication of improvement in EFS and OS. 

“The pCR rate difference of 7.5% (95% CI: 1.6, 13.4) based on all randomized patients at IA3 has questionable clinical meaningfulness,” according to the FDA. “Additionally, pCR is not an established endpoint indicative of clinical benefit, and at present, there is no conclusive evidence to link an overall improvement in pCR rate to an overall improvement in EFS at the trial level in this disease setting.” 

The agency also indicated that toxicity in this patient population is a concern, noting that “patients receiving pembrolizumab experienced increased immune-mediated AEs, including some which may be severe, irreversible, or require lifelong medication.” 

“As EFS and OS data are immature, there is inadequate justification for the entire neoadjuvant and adjuvant regimen at this time,” the FDA concluded. 


By MD /alert Staff