One problem of developing a drug for perioperative use is that hard survival data are a long time coming. Merck & Co found out yesterday that the US FDA is unlikely to be swayed by claims that a surrogate like pathological complete response (pCR) will do instead. A US advisory panel voted 10-0 that Keytruda should not be approved for neoadjuvant and adjuvant triple-negative breast cancer solely on the basis of pCR in the Keynote-522 trial. The study had a controversial design, but that was just one of the panel’s concerns, others including that pCR might not correlate with survival, and that extended immunotherapy could harm patients cured with surgery alone. The next look at a more robust Keynote-522 endpoint, event-free survival (EFS), is due in the third quarter. It is on the basis of EFS that Keytruda and Opdivo were approved for adjuvant melanoma, and the latter’s possible neoadjuvant NSCLC filing faces a similar pCR conundrum. Meanwhile, Roche’s Tecentriq has also generated positive pCR data in a neoadjuvant/adjuvant TNBC trial, Impassion-031; the group tells Evaluate Vantage it is discussing these data with global health authorities, but whether a filing has been made is unclear.
|Two perioperative studies in triple-negative breast cancer|
|Design||Neoadjuvant Keytruda + chemo vs chemo, then adjuvant Keytruda vs chemo (both blinded)||Neoadjuvant Tecentriq + chemo vs chemo (blinded), then adjuvant Tecentriq (unblinded)|
|Co-primary endpoints||pCR & EFS||pCR in ITT & pCR in ≥1% PD-L1|
|pCR data||64.8% vs 51.2% (p=0.00055)||57.6% vs 41.1% in ITT (p=0.0044)|
|EFS data||Not statistically significant at 3rd interim analysis||None generated yet|
|Drug status||Keytruda filed, 10-0 adcom vote against approval on pCR alone; 29 Mar 2021 Pdufa date||Roche "discussing data" with regulators|