1. At 24 months, more participants in the pembrolizumab group were alive without an event, compared with the placebo group.
2. 24-month survival in the pembrolizumab group was 80.9% as compared to 77.6% of placebo group patients.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Standard treatments for advanced non-small-cell lung cancer (NSCLC) includes programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) immune checkpoint inhibitors. In recent studies, it has been shown that the addition of pembrolizumab, a monoclonal antibody that binds PD-1, improved outcomes. This study examined the effect on event-free survival, overall survival (OS), and the major pathological response of neoadjuvant pembrolizumab, followed by surgery and adjuvant pembrolizumab compared with placebo. The primary outcome of this study was event-free survival and overall survival, while secondary outcomes included major pathological responses. At 24 months, more participants in the pembrolizumab group were alive without an event, compared with the placebo group (62.4% vs. 40.6%, respectively). Median event-free survival was 17.0 months in the placebo group and was not reached in the pembrolizumab group. During the study, 177 patients across both groups died. 24-month survival in the pembrolizumab group was 80.9% as compared to 77.6% of placebo group patients. The median OS in the placebo group was 45.5 months and was not reached in the pembrolizumab group. In 120 patients receiving pembrolizumab, a major pathological response was recorded, as compared to 44 patients in the placebo group. Limitations to this study include that it was not a large enough study to accommodate analysis of relative contributing effects of the neoadjuvant and adjuvant treatment components. Also, the length of time provided for follow-up is not long enough to allow interpretation of long-term outcome data. Additionally, this study explored cisplatin-based chemotherapy only, and results must be interpreted cautiously for patients receiving carboplatin-based therapies. Overall, the results from this study support that the addition of neoadjuvant and adjuvant pembrolizumab to standard chemotherapy treatment and surgical resection may improve outcomes in patients with early-stage NSCLC.
Click to read the study in the NEJM
Click to read an accompanying editorial in NEJM
Relevant Reading: Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer
In-Depth [randomized controlled trial]: This study was a phase 3, randomized controlled trial that assigned 797 adult patients receiving cisplatin-based neoadjuvant chemotherapy in a 1:1 fashion to receive either pembrolizumab (n = 397) or placebo (n = 400) in addition to chemotherapy treatment and surgery. 62.4% of patients receiving pembrolizumab were alive without an event at 24 months, compared with 40.6% of the placebo group (95% confidence interval (CI), 34.8% to 46.3%). Median event-free survival was 17.0 months in the placebo group and not reached in the pembrolizumab group (95% CI, 14.3 to 22.0 months. The hazard ratio (HR) for progression or recurrence of disease, or death, was 0.58 (95% CI, 0.46 to 0.72). At 2 years, 80.9% of patients in the pembrolizumab group were alive (95% CI, 76.2 to 84.7%), as compared to 77.6% of those in the placebo group (95% CI, 72.5 to 81.9%). Median OS was 45.5 months in the placebo group (95% CI, 42.0 to not reached), and was not reached in the pembrolizumab group (95% CI boundaries not reached). 30.2% of patients in the pembrolizumab group had a major pathological response (95% CI, 25.7 to 35.0%), as compared to 11.0% of placebo group patients (95% CI, 8.1 to 14.5%).
Image: PD
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