Pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab also appears to improve pathological responses in patients with non–small cell lung cancer.
A perioperative regimen consisting of pembrolizumab (Keytruda) and chemotherapy produced a statistically significant improvement in the primary end point of event-free survival (EFS) compared with placebo plus chemotherapy in patients with resectable stage II, IIIA, or IIIB non–small cell lung cancer (NSCLC), according to a press release on findings from the phase 3 KEYNOTE-671 trial (NCT03425643).
A prespecified interim analysis conducted by an independent data monitoring committee highlighted that neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab also produced statistically significant and clinically meaningful improvements in the secondary end points of pathological complete response (pCR) and major pathological response (mPR) vs placebo plus chemotherapy.
No new safety signals were observed in the trial.
Investigators will present detailed results from the trial at a future medical meeting. Based on the trial data, the FDA has accepted a supplemental biologics license application for pembrolizumab plus platinum-based chemotherapy followed by single-agent pembrolizumab in patients with resectable stage II, IIIA, or IIIB NSCLC.
The FDA has set a Prescription Drug User Fee Act date of October 16, 2023.
“By moving this [pembrolizumab]-based regimen into earlier stages of [NSCLC], we may be able to significantly reduce the risk of recurrence for these patients,” Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said in the press release. “This study is an important milestone, and we look forward to sharing the detailed results with the medical community as soon as possible.”
In the randomized, double-blind, phase 3 KEYNOTE-671 trial, investigators assessed neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with placebo and neoadjuvant chemotherapy followed by adjuvant placebo in patients with resectable stage II, IIIA, and IIIB NSCLC.
In the experimental arm, patients received 200 mg of pembrolizumab intravenously every 3 weeks for up to 4 cycles plus 75 mg/m2 of intravenous cisplatin on day 1 and either 1000 mg/m2 of intravenous gemcitabine on days 1 and 8 or 500 mg/m2 of intravenous pemetrexed followed by surgery and then 200 mg of intravenous pembrolizumab every 3 weeks for up to 13 cycles.
In the comparator arm, patients received saline intravenously once every 3 weeks followed by the same chemotherapy backbone as neoadjuvant therapy prior to surgery then intravenous saline for up to 13 cycles as adjuvant therapy.
The other primary end point of the KEYNOTE-671 trial was overall survival. Secondary end points included global health status or quality of life, adverse effects (AEs), perioperative complications, and treatment discontinuation due to AEs.
Patients 18 years and older who had previously untreated and pathologically confirmed resectable stage II, IIIA, or IIIB NSCLC were eligible for enrollment on the trial. Additional inclusion criteria included having available formalin-fixed paraffin embedded tumor tissue sample blocks for submission, an ECOG performance status of 0 or 1, and adequate organ function.
Patients who had NSCLC involving the superior sulcus, large cell neuroendocrine tumors, or sarcomatoid tumors were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had an active infection requiring systemic therapy, a known hypersensitivity to pembrolizumab, or a known history of human immunodeficiency virus infection.
Merck announces phase 3 KEYNOTE-671 trial met primary endpoint of event-free survival (EFS) in patients with resectable stage II, IIA, or IIIB non-small cell lung cancer. News release. Merck. March 1, 2023. Accessed March 1, 2023. bit.ly/3J0vtim