Top Line: CheckMate 816 established the benefit of adding nivolumab to neoadjuvant chemo for resectable non-small cell lung cancer (NSCLC).
The Study: The prospective single-arm phase 2 NADIM trial is here to add reproducibility. 46 patients with resectable stage IIIA NSCLC received nivo + carbo/Taxol x 3 cycles prior to surgery followed by maintenance nivo for a total of one year planned. At 3 years, overall survival was 82%, and OS was as high as 91% among those who received treatment per protocol (n=37)—5 did not proceed to surgery and an additional 4 did not receive maintenance. Let’s pause here to recognize these rates as unprecedented for locally-advanced NSCLC and likely related to an impressive pathologic complete response (pCR) rate of 63%. In fact, all patients with pCR were alive at data cutoff minus two patients who died of COVID-19. The authors don’t speculate as to why the pCR rate was so much higher than in Checkmate (24%) despite identical dosing, but we’ll point out that Checkmate is almost certainly closer to reality given its size (n=149 proceeding to surgery v n=41 here). Unlike in CheckMate, an association of benefit with PD-L1 status ≥1% could not be declared, but probably because of small numbers (n=28). Similar to CheckMate, though, both pretreatment and post-neoadjuvant treatment circulating tumor DNA levels were highly predictive of survival (more so than even RECIST here).
TBL: Pre- and post-treatment circulating tumor DNA may be an important biomarker of response in patients receiving neoadjuvant chemoimmunotherapy for resectable stage IIIA lung cancer. | Provencio, J Clin Oncol 2022