FDA Grants Pembrolizumab Sixth Indication in NSCLC

The FDA has granted a sixth non–small cell lung cancer (NSCLC) indication for pembrolizumab (Keytruda; Merck). The anti–PD-1 agent received approval¹ to treat patients with resectable NSCLC in combination with platinum-containing chemotherapy as a neoadjuvant therapy and then continued as a single agent as adjuvant treatment after surgery.

NSCLC is the most common type of lung cancer, which is the leading cause of cancer death worldwide. The 5-year survival rate in the United States for lung cancer is only 25%.²

The findings of the KEYNOTE-671 trial,³ a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, were the basis of the approval. The trial evaluated the therapy as a neoadjuvant and adjuvant treatment in patients with resectable stage II, IIIA, or IIIB NSCLC.

“Keytruda continues to change the way non-small cell lung cancer is treated across earlier and metastatic disease regardless of PD-L1 expression,” Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, said in a statement. “This approval marks a pivotal moment for the lung cancer community by providing certain patients with earlier stages of non-small cell lung cancer and healthcare providers with an important new treatment option.”

Non–small cell lung cancer is the most common type of lung cancer, which is the leading cause of cancer death worldwide.

Image credit: pakorn - stock.adobe.com

KEYNOTE-671 included 397 patients who received pembrolizumab and 400 who received placebo. The median follow-up was 25.2 months and at 2 years the event-free survival was 62.4% for pembrolizumab vs 40.6% for placebo (HR for progression, recurrence, or death, 0.58; 95% CI, 0.46-0.72; P < .001). The overall survival (OS) at 2 years was 80.9% for pembrolizumab vs 77.6% for placebo (P = .02). The median OS was 45.5 months for the placebo group and was not reached in the pembrolizumab group.

Grade 3 or higher treatment-related adverse events (TRAEs) happened in 44.9% of the pembrolizumab group and 37.3% of the placebo group. The most common (> 20%) TRAEs in both groups were:

• Nausea—54.3% for pembrolizumab vs 51.1% for placebo
• Neutrophil count decreased—42.2% for pembrolizumab vs 41.9% for placebo
• Anemia—36.1% for pembrolizumab vs 33.8% for placebo
• White cell count decreased—28.0% for pembrolizumab vs 24.6% for placebo
• Fatigue—27.3% for pembrolizumab vs 23.6% for placebo
• Constipation—26.8% for pembrolizumab vs 25.1% for placebo
• Decreased appetite—23.0% for pembrolizumab vs 22.1% for placebo

More detailed OS results are being presented at the upcoming European Society for Medical Oncology Congress 2023.

“There remains a need for treatment options to improve outcomes for patients with earlier stages of non-small cell lung cancer,” said Heather Wakelee, MD, principal investigator for KEYNOTE-671, thoracic medical oncologist and professor of medicine at Stanford University and past president of the International Association for the Study of Lung Cancer. “This important milestone has the potential to change the current treatment paradigm for resectable non-small cell lung cancer that is greater than four centimeters or has lymph node involvement, by offering an immunotherapy-based regimen that has demonstrated statistically significant improvements in overall survival and event-free survival compared to a placebo and chemotherapy regimen.”

References

1. FDA approves Keytruda (pembrolizumab) for treatment of patients with resectable (T≥4 cm or N+) NSCLC in combination with chemotherapy as neoadjuvant treatment, then continued as a single agent as adjuvant treatment after surgery. News release. Merck. October 16, 2023. Accessed October 17, 2023. https://bit.ly/403btCv

2. Lung cancer key findings. American Lung Association. Updated November 17, 2022. Accessed October 17, 2023. https://bit.ly/3FjaPXU

3. Wakelee H, Liberman M, Kato T, et al; for the KEYNOTE-671 Investigators. Perioperative pembrolizumab for early-stage non–small-cell lung cancer. N Engl J Med. 2023;389(6):491-503. doi:10.1056/NEJMoa2302983