Perioperative Pembrolizumab Shows Promising Results in Operable Non-Small Cell Lung Cancer

A randomized trial conducted to test the efficacy of perioperative pembrolizumab in operable non-small cell lung cancer (NSCLC) has shown positive results. The trial showed a 42% reduction in risk for disease recurrence or death, thereby supporting the use of PD-1 checkpoint inhibitor in stage II-III NSCLC. Although the trial did not show a significant increase in overall survival (OS), it demonstrated a favorable trend.

Positive Results in EFS Endpoint

All patients in the study received cisplatin-based neoadjuvant chemotherapy. The event-free survival (EFS) rate at 2 years was 62.4% in patients given perioperative pembrolizumab, compared with 40.6% in those assigned to placebo. The difference showed a 42% reduction in the risk for disease recurrence or death. This benefit was consistent across all subgroups, including histology and PD-L1 status.

Survival Rates Favor Pembrolizumab

At 2 years, an estimated 80.9% of patients were alive in the pembrolizumab arm versus 77.6% in the placebo arm; however, the overall survival (OS) results did not cross the significance boundary. Nevertheless, the curves showed a favorable trend.

PD-1 Checkpoint Inhibitor in Operable Patients

The data support the perioperative use of the PD-1 checkpoint inhibitor in resectable stage II-III NSCLC. Pembrolizumab is already approved by the FDA in the adjuvant setting, as is atezolizumab. Last year, the agency approved neoadjuvant nivolumab in resectable NSCLC based on the CheckMate-816 trial. These perioperative immunotherapy studies, including KEYNOTE-671, represent a major advance as new standards of care for the treatment of resectable lung cancer.

Further Study Needed to Evaluate Adjuvant Immunotherapy

The double-blind KEYNOTE-671 trial enrolled NSCLC patients with stage II-IIIB (N2) disease deemed fit for surgery. All patients received four cycles of neoadjuvant chemotherapy with IV pembrolizumab or placebo. Following surgery, patients in the two arms received up to 13 cycles of adjuvant pembrolizumab at the same dose and schedule, or placebo. The study demonstrated a favorable trend in overall survival benefit favoring a neoadjuvant plus or minus adjuvant immunotherapy approach. However, further study is needed on the additive role of adjuvant immunotherapy when patients have already received neoadjuvant chemoimmunotherapy.

The trial showed promising results for perioperative pembrolizumab in operable non-small cell lung cancer patients. The results demonstrate a significant reduction in the risk of disease recurrence or death and a favorable trend in overall survival. The data support the use of PD-1 checkpoint inhibitor in resectable stage II-III NSCLC, and the findings further reinforce the role of checkpoint blockade in operable patients. However, further study is needed to evaluate the role of adjuvant immunotherapy.