Neoadjuvant/Adjuvant Pembrolizumab Combo Improves OS in NSCLC

A total of 797 patients were randomly assigned to either the neoadjuvant pembrolizumab plus chemotherapy and adjuvant pembrolizumab group (n = 397) or the neoadjuvant placebo plus chemotherapy and adjuvant placebo group (n = 400).

Neoadjuvant pembrolizumab (Keytruda) plus chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant chemotherapy alone yielded a significant overall survival (OS) benefit for patients with resectable early-stage non–small cell lung cancer (NSCLC), according to results from the phase 3 KEYNOTE-671 trial (NCT03425643).

The 36-month OS rate estimate was 71% (95% I, 66%-76%) in the pembrolizumab group vs 64% (95% CI, 58%-69%) in the placebo group (HR, 0.72; 95% CI, 0.56-0.93; P = .0052). The median event-free survival (EFS) was 47.2 months (95% CI, 32.9-not reached [NR]) vs 18.3 months (95% CI, 14.8-22.1) in both groups, respectively (HR, 0.59; 95% CI, 0.48-0.72).

A total of 797 patients were randomly assigned to either the neoadjuvant pembrolizumab plus chemotherapy and adjuvant pembrolizumab group (n = 397) or the neoadjuvant placebo plus chemotherapy and adjuvant placebo group (n = 400). Of note, 55% of patients were younger than 65 years old, 71% were male, 87% were currently smokingor had formerly smoked, 43% had squamous histology, 70% had stage III disease, and 45% had N2 nodal status.

The median time from randomization to cutoff was 36.6 months. Of the 396 patients who were given at least 1 dose of neoadjuvant pembrolizumab plus chemotherapy, 74% were given all 4 doses, 82% underwent in-study surgery, and 73% were given at least 1 administration of neoadjuvant pembrolizumab plus chemotherapy and 13 administrations of adjuvant pembrolizumab.

Of the 399 patients who were given 1 dose of neoadjuvant placebo plus chemotherapy, 74% were given all 4 doses, 79% underwent surgery, 67% received 1 dose of adjuvant placebo, and 44% completed the regimen.

In the pembrolizumab group, 28% of patients died vs 36% in the placebo group. The median OS was 52.4 months (95% CI, 45.7-NR) in the placebo group and NR in the pembrolizumab group.At month 16, the Kaplan-Meier curves began to diverge in favor of the pembrolizumab group.

The EFS rates at 36 months were 54% (95% CI, 49%-59%) in the pembrolizumab group and 35% (95% CI, 30%-41%) in the placebo group. Overall, 44% of patients in the pembrolizumab group and 62% in the placebo group had an EFS event.

At baseline, 98% of patients in the pembrolizumab group and 98% in the placebo group completed the EORTC-QLQ-C30 questionnaire, while 69% vs 62% completed it at week 10 of the adjuvant phase. The mean quality of life scores at baseline were 73.5 points in the pembrolizumab arm and 72.8 points in the placebo arm.

In the pembrolizumab arm, the least square mean (LSM) change was –9.3 points (95% CI –11.7 to –6.9) vs –10.7 points (95% CI, –13.1 to –8.4) in the placebo arm at week 11 in the neoadjuvant phase. In the adjuvant phase at week 10, the LSM changes were –1.5 points (95% CI, –3.7 to 0.6) vs –3.7 points (95% CI, –6.0 to –1.5).

Treatment-related adverse effects (TRAEs) were noted in 97% of patients in the pembrolizumab arm and 95% in the placebo arm, and grade 3 or higher TRAEs occurred in 45% vs 38%. Four patients in the pembrolizumab group died due to TRAEs vs 3 in the placebo group. Discontinuations due to TRAEs were noted in 14% of patients in the pembrolizumab group and 5% in the placebo group.

The most common TRAEs between the pembrolizumab and placebo groups included nausea (55% vs 51%), decreased neutrophil count (43% vs 42%), and anemia (36% vs 34%). TRAEs that were grade 3 or higher included decreased neutrophil count (21% vs 20%), anemia (7% vs 6%), decreased platelet count (5% vs 6%), and decreased white cell count (5% vs 6%).

Reference

Spicer JD, Garassino MC, Wakelee H, et al. Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone in patients with early-stage non-small-cell lung cancer (KEYNOTE-671): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;404(10459):1240-1252. doi:10.1016/S0140-6736(24)01756-2