Top Line: Checkmate 816 changed the landscape of definitive surgery for non-small cell lung cancer (NSCLC) with neoadjuvant chemoimmunotherapy.
The Study: As a reminder, it demonstrated the addition of nivolumab to 3 cycles of a neoadjuvant platinum-doublet chemotherapy significantly prolonged the primary outcome of event free survival (EFS) from 21 → 32 months for patients with resectable, stage IB-IIIA NSCLC. Never to leave a potential market share on the table, Merck is now reporting its own version subbing pembro for nivo in KEYNOTE-671. In this double-blind phase 3 trial 797 patients with resectable stage II to even IIIB (if N2, ~45%) NSCLC received 4 cycles of neoadjuvant cisplatin-based chemotherapy +/- concurrent neoadjuvant pembro and further post-op adjuvant pembro for 13 q3-week cycles. The latter is a key difference in the Checkmate trial, which only used neoadjuvant immunotherapy with no additional maintenance therapy. The two primary endpoints were event-free survival and overall survival. At 24 months, event-free survival was indeed significantly improved (41 → 62%) while overall survival was not (78 → 81%). The pathologic complete response rate was also higher with chemoimmunotherapy (18.1% v 4%). The rate of grade 3+ toxicity was 45% with chemoimmunotherapy compared to 38% with chemo. The outcomes, at least numerically, were pretty comparable to the Checkmate trial raising the question of whether those extra 13 cycles of pembro are necessary. The KEYNOTE authors argued that the EFS benefit was seen in those with favorable response and those without–suggesting poor responders may still benefit from maintenance therapy. They also tried to argue that the hazard ratio for disease progression among nonresponders in their study was lower than in Checkmate.
TBL:In KEYNOTE-671, perioperative pembrolizumab improved event free survival compared to neoadjuvant chemotherapy alone for resectable NSCLC. | Wakelee, N Engl J Med 2023
The Study: As a reminder, it demonstrated the addition of nivolumab to 3 cycles of a neoadjuvant platinum-doublet chemotherapy significantly prolonged the primary outcome of event free survival (EFS) from 21 → 32 months for patients with resectable, stage IB-IIIA NSCLC. Never to leave a potential market share on the table, Merck is now reporting its own version subbing pembro for nivo in KEYNOTE-671. In this double-blind phase 3 trial 797 patients with resectable stage II to even IIIB (if N2, ~45%) NSCLC received 4 cycles of neoadjuvant cisplatin-based chemotherapy +/- concurrent neoadjuvant pembro and further post-op adjuvant pembro for 13 q3-week cycles. The latter is a key difference in the Checkmate trial, which only used neoadjuvant immunotherapy with no additional maintenance therapy. The two primary endpoints were event-free survival and overall survival. At 24 months, event-free survival was indeed significantly improved (41 → 62%) while overall survival was not (78 → 81%). The pathologic complete response rate was also higher with chemoimmunotherapy (18.1% v 4%). The rate of grade 3+ toxicity was 45% with chemoimmunotherapy compared to 38% with chemo. The outcomes, at least numerically, were pretty comparable to the Checkmate trial raising the question of whether those extra 13 cycles of pembro are necessary. The KEYNOTE authors argued that the EFS benefit was seen in those with favorable response and those without–suggesting poor responders may still benefit from maintenance therapy. They also tried to argue that the hazard ratio for disease progression among nonresponders in their study was lower than in Checkmate.
TBL:In KEYNOTE-671, perioperative pembrolizumab improved event free survival compared to neoadjuvant chemotherapy alone for resectable NSCLC. | Wakelee, N Engl J Med 2023