ESMO 2023 Update – CheckMate 77T: Another Phase 3 Trial of Perioperative Immunotherapy Improving Event-Free Survival for Resectable Stage II-III Non-Small Cell Lung Cancer
Author:
Lei Deng, MD
Assistant Professor/Medical Oncologist
Thoracic, Head & Neck Medical Oncology
University of Washington/Fred Hutchinson Cancer Center
Key Points:
- In phase 3 CheckMate 77T, resectable stage II-IIIB NSCLC received 4 cycles of neoadjuvant nivolumab (or placebo) + chemotherapy followed by adjuvant nivolumab (or placebo) for a year
- The prespecified interim analysis at ESMO 2023 showed statistically improved event-free survival (HR, 0.58; median not reached vs 18.4 months) and pathological complete response rate (25.3% vs. 4.7%)
- Definitive surgery rates were 78% vs. 77% in the nivolumab and placebo group, respectively, highlighting the importance of patient selection preoperatively.
CheckMate-816 of 3 cycles of neoadjuvant nivolumab + surgery improved event-free survival and is a standard of care for early-stage non-small cell lung cancer1. At this year’s 2023 ESMO congress, CheckMate 77T was presented on the efficacy of perioperative nivolumab for those patients (Abstract Number: LBA1).
This randomized, double-blind, placebo-controlled phase 3 trial included 661 patients of stage II-IIIB (AJCC 8). Patients were randomized to receive neoadjuvant nivolumab (or placebo) plus chemotherapy for 4 cycles followed by adjuvant nivolumab (or placebo) for a year. The median follow-up time was 25.4 months. The event-free survival (EFS) was improved significantly from 18.4 months in the placebo arm to not reached in the nivolumab arm (HR [97.36% CI], 0.58 [0.42–0.81]). The pathological complete response and major pathological response rate was also improved to 25.3% and 35.4%, respectively, consistent with CheckMate 816. Among all patients, 78% vs 77% underwent definitive surgery in the nivo and placebo arm, respectively. PD-L1 status appears to be correlated with EFS improvement. Patients who achieve pCR have excellent outcomes, similar to CheckMate 816.
The rate of not receiving is high and appear comparable in both nivolumab and placebo arm. However, in the chemotherapy only era, the NATCH trial compared the surgery alone vs. neoadjuvant chemotherapy vs. adjuvant directly. It showed higher surgery rate of 95.2% vs. 91% vs. 95.7%, respectively. In upfront surgery arms, about 5% of patients could not undergo surgery and 9% of patients could not after neoadjuvant chemotherapy2. These data suggest that there might be an overoptimism of in the neoadjuvant chemoimmunotherapy trials and possibly enrolling more borderline respectable patients, highlighting the importance of patient selection. The concept of converting borderline resectable to resectable by neoadjuvant chemoimmunotherapy should be investigated with caution.
- Forde PM, Spicer J, Lu S, et al. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med 2022;386:1973-1985.
- Felip E, Rosell R, Maestre JA, et al. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer. J Clin Oncol 2010;28:3138-3145.
