A statistically significant overall survival benefit was observed with perioperative pembrolizumab in the phase 3 KEYNOTE-671 trial for patients with stage II, IIIA or IIIB non–small cell lung cancer.
Pembrolizumab (Keytruda) as a perioperative treatment regimen for patients with resectable stage II, IIIA or IIIB (T3-4N2) non–small cell lung cancer (NSCLC) met its dual primary end point of overall survival (OS), according to data from the prespecified interim analysis of the phase 3 KEYNOTE-671 trial (NCT03425643).1
Treatment with neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab as a single agent yielded a statistically significant and clinically meaningful improvement in OS vs neoadjuvant placebo plus chemotherapy followed by adjuvant placebo among this patient population.
No new safety signals were identified in the study and the safety profile of pembrolizumab remained consistent with that observed in previously reported studies. Full results from the analysis are expected to be presented at the European Society for Medical Oncology (ESMO) Congress 2023 and shared with regulatory authorities.
“We have a lot ahead of us to try to determine the question of who should go to surgery, who needs neoadjuvant, who needs adjuvant, as opposed to looking at all of the different options that we have. But we do have a wealth of opportunities, assuming approvals, and there are a lot of steps forward for our patients. These results look pretty encouraging, so I think we are going to be making an impact,” Heather Wakelee, MD, from Stanford University School of Medicine and the Stanford Cancer Institute, told Targeted OncologyTM.
The randomized, double-blind, phase 3 KEYNOTE-671 trial is investigating the dual primary end points of event-free survival and OS, along with the key secondary end points of pathological complete response (pCR) and major pathologic response (mPR).
A total of 786 patients were enrolled in the study and randomly assigned in a 1:1 ratio. In the first arm, patients were treated with pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 4 cycles with chemotherapy as neoadjuvant therapy prior to surgery, followed by pembrolizumab 200 mg IV Q3W for up to 13 cycles as adjuvant therapy post-surgery. The second arm of the trial received placebo plus chemotherapy as neoadjuvant therapy prior to surgery, followed by placebo as adjuvant therapy post-surgery.
At the first interim analysis, investigators announced that 1 of the dual primary end points, EFS, was met, as well as its key secondary end points of pCR and mPR, according to data presented at the 2023 American Society of Clinical Oncology (ASCO).2 The 24-month EFS rate was 62.4% with pembrolizumab plus chemotherapy and adjuvant pembrolizumab vs 40.6% for placebo plus chemotherapy (HR, 0.58; 95% CI, 0.46-0.72; P < .00001). The mPR rate was 30.2% (95% CI, 25.7%-35.0%) with pembrolizumab compared with 11.0% (95% CI, 8.1%-14.5%) with placebo (Δ, 19.2%; 13.9%-24.7%; P < .00001). Further, the pathological complete pCR rate was 18.1% (95% CI, 14.5%-22.3%) with pembrolizumab vs 4.0% (95% CI, 2.3%-6.4%) for placebo (Δ, 14.2%; 95% CI, 10.1%-18.7%; P < .00001).
Based on these data, the FDA accepted a new supplemental biologics license application for perioperative pembrolizumab with chemotherapy and set a Prescription Drug User Fee Act (PDUFA), or target action, date of October 16, 2023.1
“This is a significant milestone in the treatment of resectable non-small cell lung cancer, as it represents the first phase 3 study to show a statistically significant overall survival benefit for these patients with stage II, IIIA or IIIB [T3-4N2] non–small cell lung cancer. These results build upon the previously reported event-free survival data, and demonstrate the potential for this [pembrolizumab]-based regimen to help extend the lives of these patients,” said Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, in a press release.
In addition to KEYNOTE-671, Merck has an extensive clinical development program in lung cancer which is evaluating treatment options for earlier stages of NSCLC and small cell lung cancer. These studies include KEYNOTE-091 (NCT02504372), KEYNOTE-867 (NCT03924869), KEYLYNK-012 (NCT04380636), KEYVIBE-006 (NCT05298423), and KEYLYNK-013 (NCT04624204).
“We're excited by the progress we have made to help patients with earlier stages of non-small cell lung cancer, who are in need of additional treatment options,” added Green.