Compared to placebo plus chemotherapy, nivolumab plus chemotherapy had also improved event-free survival and both pathological complete response and major pathologic response rates.
A phase 3 study, CheckMate 77T (NCT04025879), compared the efficacy of neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab with neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo in patients with previously untreated resectable stage II through IIIB non–small cell lung cancer (NSCLC). The results were presented by investigators at the European Society for Medical Oncology Congress 2023 in Madrid, Spain. CheckMate 77T is a randomized, double-blind study that had event-free survival (EFS) as a primary end point, and pathological complete response (pCR), major pathologic response (MPR), overall survival, and safety as secondary end points.
“A perioperative treatment approach including adjuvant nivolumab could potentially further reduce the risk of relapse and improve clinical benefit in patients with resectable NSCLC,” said lead study author Tina Cascone, MD, PhD, associate professor of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, in an interview with Pharmacy Times. “The CheckMate 77T study is the first perioperative phase 3 study that builds on the current standard of care of neoadjuvant nivolumab plus chemotherapy and investigated whether a perioperative approach that includes immunotherapy with nivolumab before and after tumor resection could further reduce the risk of relapse and improve clinical benefit in patients with resectable NSCLC.”
Adults with untreated resectable stage II through IIIB NSCLC were randomized to receive 360 mg of nivolumab every 3 weeks (Q3W) plus 4 cycles of platinum-doublet chemotherapy followed by surgery and 480 mg of adjuvant nivolumab every 4 weeks (Q4W) for 1 year, or placebo Q3W plus 4 cycles of platinum-doublet chemotherapy followed by surgery and adjuvant placebo Q4W for 1 year. There were 229 patients in the nivolumab group and 232 in the placebo group.
“Optimizing the administration of immunotherapy for resectable NSCLC is an important goal, particularly given the tendency of resectable NSCLC to recur after surgical resection. Nivolumab plus chemotherapy is the standard-of-care neoadjuvant treatment for eligible patients with resectable NSCLC, having demonstrated statistically significant and clinically meaningful improvements in event-free survival and pathological complete response rates compared with chemotherapy in the CheckMate 816 study [NCT02998528],” said Cascone.
At a median follow-up of 15.7 months, the nivolumab group had a significantly improved EFS compared with the placebo group (median, not reached [95% CI, 28.9 months-not reached] vs 18.4 months [95% CI, 13.6-28.1]; HR, 0.58 [97.36% CI, 0.42-0.81]; P = .00025). Further, there were also improved pCR (25.3% vs 4.7%; odds ratio [OR], 6.64; 95% CI, 3.40-12.97) and MPR (35.4% vs 12.1%; OR, 4.01; 95% CI, 2.48-6.49) rates in the nivolumab group compared with the placebo group. In addition, definitive surgery rates were 78% and 77% in the nivolumab group and placebo group, respectively.
“The results of our study are very encouraging and support perioperative nivolumab as a potential new treatment option that may reduce the risk of disease recurrence and improve long-term outcomes in patients with resectable NSCLC,” said Cascone.
Treatment-emergent adverse effects (TEAEs) were grade 3 and 4 in severity. Approximately 32% of patients in the nivolumab group and 25% of patients in the placebo group had experienced TEAEs, and surgery-related AEs were experienced by 12% of patients in both groups. No new safety signals were noted in the nivolumab-treated group.
“Our next steps will focus on identifying patient and disease characteristics and attributes that will tell us which individuals benefit most from a neoadjuvant chemoimmunotherapy approach alone and which require more intensified adjuvant treatments including the perioperative CheckMate 77T strategy or a ‘switch-agent’ type of adjuvant regimen,” said Cascone.
Cascone T, Awad MM, Spicer JD, et al. CheckMate 77T: phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIb NSCLC. Ann Oncol. 2023;34(suppl 2):S1295. doi:10.1016/j.annonc.2023.10.050