Keytruda + chemotherapy before surgery and continued as a single agent after surgery reduced the risk of event-free survival events by 42% versus pre-operative chemotherapy in resectable Stage II, IIIA or IIIB NSCLC – Merck Inc

Merck known as MSD outside of the United States and Canada, announced positive results from the pivotal Phase III KEYNOTE-671 trial evaluating Keytruda, Merck’s anti-PD-1 therapy, as a perioperative treatment regimen, which includes treatment before surgery (neoadjuvant) and after surgery (adjuvant), for patients with resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC).

After a median follow-up of 25.2 months, neoadjuvant Keytruda plus chemotherapy followed by resection and adjuvant single-agent Keytruda significantly improved EFS,(event free survival) reducing the risk of disease recurrence, progression or death by 42% (HR=0.58 [95% CI, 0.46-0.72]; p<0.00001) for patients with resectable stage II, IIIA or IIIB NSCLC versus neoadjuvant placebo plus chemotherapy followed by adjuvant placebo. For patients who received the Keytruda-based regimen, median EFS was not reached (95% CI, 34.1-NR) versus 17 months (95% CI, 14.3-22) for patients who received chemotherapy alone.

The trial is continuing to allow for additional follow-up of overall survival (OS), the other dual primary endpoint. A favorable trend in OS was observed for the Keytruda regimen versus pre-operative chemotherapy (HR 0.73 [95% CI, 0.54-0.99]; p=0.02124); with only 177 events, these OS data are not mature and did not reach statistical significance at the time of this interim analysis.

The safety profile of the Keytruda regimen was consistent with the safety profile in earlier stages and metastatic NSCLC, with no new safety concerns identified. These results are being presented during a clinical science symposium, The Promise of Neoadjuvant Immunotherapy Across Solid Tumors, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA100) and are also being simultaneously published in the New England Journal of Medicine.

While achieving pCR is a predictor of better outcomes, an exploratory subgroup analysis showed the reduction in EFS events with the Keytruda perioperative regimen was observed for patients with or without pCR (with pCR: HR=0.33 [95% CI, 0.09-1.22]; without pCR: HR=0.69 [95% CI, 0.55-0.86]).

“Historically, more than half of people with earlier stages of non-small cell lung cancer that has been surgically removed will experience recurrence,” said Dr. Heather Wakelee, thoracic medical oncologist and professor of medicine at Stanford Medicine, president of the International Association for the Study of Lung Cancer and principal investigator for KEYNOTE-671. “Results showed that a pembrolizumab-based regimen before and after surgery significantly reduced the risk of recurrence, progression or death by 42 percent versus pre-operative chemotherapy, regardless of PD-L1 expression and with or without a pathological complete response. These event-free survival data are very encouraging and support the potential of this perioperative approach for patients with resectable stage II, IIIA or IIIB non-small cell lung cancer.

“These results are meaningful for the community of thoracic surgeons given the need for additional treatment options that can improve event-free survival for patients with resectable stage II, IIIA or IIIB non-small cell lung cancer,” said Dr. Jonathan Spicer, associate professor of surgery, McGill University, attending surgeon, division of thoracic and upper gastrointestinal surgery, Montreal General Hospital, McGill University Health Centre and KEYNOTE-671 investigator. “Notably, the results showed that the Keytruda-based perioperative regimen did not impact the opportunity for a complete resection and improvements were seen regardless of if they achieved a pathological complete response or not.”

Merck previously announced that, based on these results, the FDA has accepted a new supplemental Biologics License Application (sBLA) for Keytruda for the treatment of patients with resectable stage II, IIIA, or IIIB (T3-4N2) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment. The FDA has set a Prescription Drug User Fee Act, or target action, date of October 16, 2023.

See- “Perioperative Pembrolizumab for Early-Stage Non–Small-Cell Lung Cancer”- Heather Wakelee, M.D., Moishe Liberman, M.D., Ph.D., Terufumi Kato, M.D., Masahiro Tsuboi, M.D., Ph.D., et al., for the KEYNOTE-671 Investigators.DOI: 10.1056/NEJMoa2302983.