Perioperative Pembrolizumab Plus Chemo Wins Approval in China for Resectable Stage II/III NSCLC

China’s National Medical Products Administration (NMPA) has approved pembrolizumab (Keytruda) in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by pembrolizumab monotherapy as adjuvant treatment after surgery, for patients with resectable stage II, IIIA, or IIIB non–small cell lung cancer (NSCLC).1

The regulatory decision was supported by data from the phase 3 KEYNOTE-671 trial (NCT03425643), which showed that the pembrolizumab regimen reduced the risk of death by 28% compared with neoadjuvant placebo plus chemotherapy, followed by adjuvant placebo, irrespective of PD-L1 status (HR, 0.72; 95% CI, 0.56-0.93; one-sided P = .0103). Patients treated with the pembrolizumab regimen experienced a median overall survival (OS) that was not reached (NR; 95% CI, NR-NR) compared with 52.4 months (95% CI, 45.7-NR) for those treated with the placebo regimen.

The pembrolizumab regimen also produced a statistically significant improvement in event-free survival (EFS) compared with chemotherapy alone (HR, 0.58; 95% CI, 0.46-0.72; P < .0001).

“This approval marks [pembrolizumab’s] fourth lung cancer indication in China, embarking on a new journey of treating certain patients with earlier-stage NSCLC,” Anna Van Acker, senior vice president of MSD and president of MSD in China, stated in a news release. “[Pembrolizumab] has established an important role in immunotherapy for advanced NSCLC with its three previously approved indications in China, but there are still significant unmet medical needs for certain patients with earlier-stage NSCLC, as lung cancer remains China's leading cause of cancer incidence and mortality. We are thrilled to introduce this new treatment option and remain committed to advancing innovation to help more Chinese patients.”

In October 2023, the FDA approved pembrolizumab in combination with platinum-containing chemotherapy as neoadjuvant treatment, and with continuation of pembrolizumab monotherapy as post-surgical adjuvant treatment for patients with resectable NSCLC.2 That regulatory decision was also based on data from KEYNOTE-671.

KEYNOTE-671 was a randomized, double-blind, phase 3 trial that enrolled patients with resectable stage II, IIIA, or IIIB (T3-4N2) NSCLC.1 Other key inclusion criteria consisted of an ECOG performance status of 0 to 1 within 10 days of randomization and adequate organ function.3

Patients were excluded if they had NSCLC involving the superior sulcus, large cell neuroendocrine cancer, or a sarcomatoid tumor. Other key exclusion criteria comprised a history of or current pneumonitis or interstitial lung disease requiring steroids; an active infection requiring systemic therapy; prior allogenic tissue or solid organ transplant; active autoimmune disease requiring systemic therapy within 2 years of enrollment; and prior therapy with an anti–PD-1, –PD-L1, or –PD-L2 agent, or any agent directed to another co-inhibitory T-cell receptor.

Investigators enrolled 797 patients who were randomly assigned 1:1.1 During the neoadjuvant phase, patients in the experimental arm received pembrolizumab at 200 mg once every 3 weeks plus cisplatin at 75 mg/m2 on day 1 of each cycle and either gemcitabine at 1000 mg/m2 on days 1 and 8 of each cycle or pemetrexed at 500 mg/m2 on day 1 of each cycle. Patients in this arm then continued with 200 mg of pembrolizumab once every 3 weeks for up to 13 cycles as adjuvant therapy. In the control arm, patients received the same chemotherapy regimen in combination with placebo, then placebo once every 3 weeks for 13 cycles as adjuvant therapy.

EFS and OS served as the trial’s dual primary end points. Secondary end points included pathologic complete response rate and major pathological response rate.

Regarding safety, adverse effects for the pembrolizumab-based regimen were generally similar to toxicities reported in patients across various tumor types who have been treated with pembrolizumab plus chemotherapy.

References

1. Merck’s Keytruda (pembrolizumab) approved in China in combination with chemotherapy as neoadjuvant treatment, then continued as monotherapy after surgery as adjuvant treatment for patients with resectable stage II, IIIA or IIIB NSCLC. News release. Merck. December 16, 2024. Accessed December 16, 2024. https://www.merck.com/news/mercks-keytruda-pembrolizumab-approved-in-china-in-combination-with-chemotherapy-as-neoadjuvant-treatment-then-continued-as-monotherapy-after-surgery-as-adjuvant-treatment-for-patien/
2. FDA approves neoadjuvant/adjuvant pembrolizumab for resectable non-small cell lung cancer. FDA. October 16, 2023. Accessed December 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvant-adjuvant-pembrolizumab-resectable-non-small-cell-lung-cancer
3. Efficacy and safety of pembrolizumab (MK-3475) with platinum doublet chemotherapy as neoadjuvant/​adjuvant therapy for participants with resectable stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer (MK-3475-671/​KEYNOTE-671). ClinicalTrials.gov. Updated December 3, 2024. Accessed December 16, 2024. https://clinicaltrials.gov/study/NCT03425643