Top Line: The single-arm phase 2 NADIM trial supported findings from Checkmate 816 and KEYNOTE-671 by demonstrating impressive pathologic complete responses and survival times with adding immune checkpoint inhibition to neoadjuvant chemo for resectable non-small cell lung cancer (NSCLC).
The Study: We now have results of the follow-on, two-arm phase 2 NADIM II trial where 86 patients receiving neoadjuvant platinum-based chemo for resectable stage IIIA or IIIB NSCLC were randomized 2:1 to +/- the addition of concurrent and maintenance nivolumab. Important distinctions from Checkmate 816 are (1) the inclusion of N2 disease (66% of enrollees) and (2) the addition of maintenance nivolumab for an additional 6 months after surgery. First of all, the addition of nivo increased the proportion of patients proceeding to surgery from 69 → 93%. The primary endpoint of complete pathologic response was increased from 7 → 37%, higher than that seen with pembro on KEYNOTE-671 (18%) or with nivo on Checkmate 816 (24%) but considerably lower than the eyebrow raising rate seen on the initial NADIM trial (63%). The only potential hypothesis for the discrepancy in NADIM and NADIM II was the former used a higher dose of carbo (AUC 6 v 5). This is particularly important in light of the fact no complete responder (n=23) had evidence of disease at 2 years. Progression-free survival was increased at 24 months from 41 → 67% and overall survival, remarkably, from 64 → 85%. This all places a big question mark on which definitive treatment should be paired with immunotherapy in the management of stage IIIA-IIIB NSCLC, surgery or radiation?
TBL: This randomized phase 2 trial indicates the addition of perioperative nivolumab to neoadjuvant chemo prior to resection of stage IIIA-IIIB NSCLC improves survival. | Provencio, N Engl J Med 2023
The Study: We now have results of the follow-on, two-arm phase 2 NADIM II trial where 86 patients receiving neoadjuvant platinum-based chemo for resectable stage IIIA or IIIB NSCLC were randomized 2:1 to +/- the addition of concurrent and maintenance nivolumab. Important distinctions from Checkmate 816 are (1) the inclusion of N2 disease (66% of enrollees) and (2) the addition of maintenance nivolumab for an additional 6 months after surgery. First of all, the addition of nivo increased the proportion of patients proceeding to surgery from 69 → 93%. The primary endpoint of complete pathologic response was increased from 7 → 37%, higher than that seen with pembro on KEYNOTE-671 (18%) or with nivo on Checkmate 816 (24%) but considerably lower than the eyebrow raising rate seen on the initial NADIM trial (63%). The only potential hypothesis for the discrepancy in NADIM and NADIM II was the former used a higher dose of carbo (AUC 6 v 5). This is particularly important in light of the fact no complete responder (n=23) had evidence of disease at 2 years. Progression-free survival was increased at 24 months from 41 → 67% and overall survival, remarkably, from 64 → 85%. This all places a big question mark on which definitive treatment should be paired with immunotherapy in the management of stage IIIA-IIIB NSCLC, surgery or radiation?
TBL: This randomized phase 2 trial indicates the addition of perioperative nivolumab to neoadjuvant chemo prior to resection of stage IIIA-IIIB NSCLC improves survival. | Provencio, N Engl J Med 2023