Achieving an Objective Response Following Two Cycles of Neoadjuvant Chemotherapy Plus Anti-PD-(L)1 Inhibitors Might...

Neoadjuvant chemotherapy plus anti-programmed death (ligand)-1 (anti-PD-(L)1) inhibitors (chemoimmunotherapy) for early-stage nonsmall cell lung cancer (NSCLC) is under investigation, but differences in pathological response rates between patients who achieved objective responses after 2 versus 3-6 cycles remain unclear.

We retrospectively enrolled 481 stage II-III NSCLC patients who had 2-6 cycles of neoadjuvant chemoimmunotherapy followed by surgery (June 2018-February 2024). The primary outcomes compared the pathological response (pathological complete response [pCR] and major pathological response [MPR]) between the 2-cycle (n = 99) and 3-6-cycle (n = 382) groups in patients who achieved objective response as well as between objective response rate (ORR) and non-ORR groups.

For patients achieving objective response, pCR (52.7% vs. 47%; odds ratio [OR]: 1.26; 95% confidence interval [CI]: 0.70-2.25; P = .439) and MPR (78.2% vs. 69.9%; OR: 1.54; 95% CI, 0.77-3.08; P = .220) rates in the 2-cycle group were not inferior to the 3-6 cycle group. The ORR group had higher pCR (52.7% vs. 31.8%; OR: 2.39; 95% CI, 1.05-5.46; P = .039) and MPR (78.2% vs. 56.8%; OR: 2.72; 95% CI, 1.14-6.53; P = .025) rates than the non-ORR group for patients undergoing 2 cycles of neoadjuvant therapy. Similar trends for pCR (47.0% vs. 32.8%; OR: 1.82; 95% CI, 1.15-2.87; P = .01) and MPR (69.9% vs. 49.1%; OR: 2.41; 95% CI, 1.54-3.77; P < .001) also occurred in patients undergoing 3-6 cycles of neoadjuvant therapy.

Achieving an objective response following 2 cycles of neoadjuvant chemoimmunotherapy may predict optimal pathological responses in stage II-III NSCLC.