Positive results have emerged from recent clinical trials evaluating perioperative pembrolizumab in both non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), marking potential advancements in the treatment of these cancers. The KEYNOTE-671 trial demonstrated significant survival benefits in early-stage NSCLC, while the KEYNOTE-689 trial showed improved event-free survival in advanced HNSCC. These findings suggest a promising role for pembrolizumab in earlier stages of these diseases.
Pembrolizumab Improves Survival in Resectable NSCLC
The KEYNOTE-671 trial, a randomized Phase III study, investigated the efficacy of pembrolizumab (Keytruda) in conjunction with neoadjuvant chemotherapy and adjuvant pembrolizumab in patients with operable, early-stage NSCLC. Published in The Lancet, the results indicated a significant improvement in overall survival. At the second interim analysis:
- 71% of patients in the pembrolizumab group were alive 36 months after trial inclusion, compared to 64% in the placebo group.
- Median event-free survival was 47 months in the pembrolizumab group and 18 months in the placebo group.
Grade 3–5 treatment-related adverse events occurred in 45% of participants in the pembrolizumab group and 38% in the placebo group.
"Non-small cell lung cancer is the most common form of lung cancer, and this is the first paper in 30 years of research in this field to show a benefit in terms of overall survival, i.e., lifespan for patients, associated with the addition of neoadjuvant immunotherapy to standard treatment for this type of cancer," said Dr. Jonathan Spicer, lead author and thoracic surgeon at McGill University Health Centre (MUHC).
The trial enrolled 797 adult participants with surgically removable stage II or III NSCLC. Half received neoadjuvant pembrolizumab plus cisplatin-based chemotherapy followed by surgery and adjuvant pembrolizumab; the other half received neoadjuvant chemotherapy and surgery alone, with a placebo instead of pembrolizumab.
Perioperative Pembrolizumab Enhances Event-Free Survival in Advanced HNSCC
In a separate development, Merck announced positive findings from the Phase 3 KEYNOTE-689 trial, evaluating pembrolizumab in patients with stage III or IVA resected head and neck squamous cell carcinoma (LA-HNSCC). The trial met its primary endpoint of event-free survival (EFS) with perioperative pembrolizumab.
"These results are substantial, as KEYNOTE-689 marks the first positive trial in 2 decades for patients with resected, locally advanced head and neck squamous cell carcinoma," said Dr. Marjorie Green, Senior Vice President at Merck Research Laboratories.
The randomized, active-controlled, open-label study included 704 patients across 192 global sites. Patients received neoadjuvant pembrolizumab, followed by pembrolizumab plus standard-of-care radiotherapy (with or without cisplatin) as adjuvant therapy, and then as maintenance. The primary endpoint was EFS, and secondary endpoints included major pathological response, overall survival (OS), pathological complete response, and incidence of adverse events.
The pembrolizumab-based treatment also produced a trend toward improved overall survival (OS) vs treatment in the comparator arm, although these data did not reach statistical significance among patients with a PD-L1 combined positive score (CPS) of 10 or higher at the time of analysis.
Implications for Clinical Practice
These findings from the KEYNOTE-671 and KEYNOTE-689 trials suggest that perioperative pembrolizumab could become a valuable treatment option for patients with early-stage NSCLC and advanced HNSCC. The improved survival outcomes and manageable safety profiles support the use of this immunotherapy in conjunction with standard treatments. Further research and regulatory review will be essential to integrate these findings into clinical practice.
