Episode 5: KEYNOTE-671 demonstrates the OS benefit of perioperative immunochemotherapy in early-stage NSCLC

In this episode of WND on lung cancer, Professor Johan Vansteenkiste from University Hospitals Leuven and Professor Mariana Brandao, medical oncologist at Institut Jules Bordet in Brussels, will discuss the KEYNOTE-671 trial regarding the addition of pembrolizumab in the peri-operative setting for early-stage NSCLC.

While previous trials focused on DFS or EFS as primary endpoints, the KEYNOTE-671 trial introduces the first-ever OS data on perioperative immunotherapy. This data is crucial for evaluating the risk-benefit ratio of this treatment, considering the potential for cure through surgery or chemotherapy alone.

Patients in the KEYNOTE-671 trial received neoadjuvant chemotherapy plus either a placebo or pembrolizumab, followed by surgery and post-surgery treatment with either a placebo or pembrolizumab for one year. Previously reported EFS data showed a favourable hazard HR of 0.58 for chemo-immunotherapy over chemotherapy alone, indicating strong, significant, and clinically relevant results. While this regimen is becoming a standard approach, OS data remains critical. With a median follow-up of 36.6 months, pembrolizumab treatment showed an HR of 0.72 and improved OS for patients receiving immuno-chemotherapy with 71%, compared to 64% for chemotherapy alone. Importantly, the OS benefit was consistent across different histologies and stages (II, IIIa, IIIb).

There was a trend suggesting that higher PD-L1 values were associated with better outcomes. Although the HR of 0.91 in negative tumours is less convincing, it still suggests that peri-operative treatment improves OS in all patients. The benefit of immunotherapy on DFS appears independent of the patient’s PD-L1 status, as observed in both this trial and the CheckMate-77T trial, another perioperative trial, especially considering the variability of PD-L1 expression between tumours.

The OS data emphasize the importance of immunotherapy in treating early-stage lung cancer before surgery. While chemo-immunotherapy slightly reduces the occurrence of patients not proceeding to surgery (10-15%), in such cases, straightforward surgery might be the preferred option. Patient selection is critical, with the decision about resectability made before initiating any treatment. This decision requires a multidisciplinary tumour board comprising medical oncologists, pulmonologists, surgeons, and radiotherapists to offer the best possible treatment for the patient.