A second interim analysis of the KEYNOTE-671 trial has shown that adding perioperative pembrolizumab to neoadjuvant chemotherapy for early-stage non-small-cell lung cancer (NSCLC) is effective and safe. This combination of medication showed significant overall survival benefit for patients who lived longer without cancer progression, recurrence or death and increased health-related quality of life.
This follows the results of the first interim analysis which found that adding perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved event-free survival in participants with early-stage NSCLC but did not improve overall survival.
The global phase 3 trial was undertaken at 189 medical centres between May 2018 and Dec 2021 and involved 797 participants. All participants were 18 or older and had resectable stage II, IIIA, or IIIB (N2) NSCLC.
Patients were randomly assigned to one of two medication groups, with 397 undertaking treatment with pembrolizumab: four cycles of neoadjuvant pembrolizumab (200 mg administered intravenously every three weeks) plus cisplatin-based chemotherapy followed by surgery and 13 cycles of adjuvant pembrolizumab (200 mg administered intravenously every three weeks).
The control group had four cycles of neoadjuvant placebo (administered intravenously every three weeks) plus cisplatin-based chemotherapy followed by surgery and 13 cycles of adjuvant placebo (administered intravenously every three weeks).
Groups were stratified based on disease stage, levels of the PD-L1 protein in cancer cells, lung cancer types and geographical regions. Researchers compared rates of overall survival and event-free survival between the two groups.
At 36 months, overall survival rates were 71% (95% CI 66–76) in the pembrolizumab group and 64% (95% CI 58–69) in the placebo group. Median event-free survival was 47.2 months in the pembrolizumab group and 18.3 months in the placebo group.
Serious side effects (grade 3–5) were more common in the pembrolizumab group (45%) compared to the placebo group (38%). Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group and three (1%) participants in the placebo group.
The authors concluded that the use of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab was beneficial in patients with resectable, early-stage NSCLC due to significant overall survival benefits and the manageable safety profile, supporting its use in this patient group.
Reference
Spicer, J 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. The Lancet 2024; Sept. 28: DOI: 10.1016/S0140-6736(24)01756-2.
