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Pembrolizumab was found to significantly improve disease-free survival vs placebo when used in the adjuvant treatment of patients with stage IB to IIIA non–small cell lung cancer following surgical resection, meeting 1 of the dual primary end points of the phase 3 KEYNOTE-091 trial.
Pembrolizumab (Keytruda) was found to significantly improve disease-free survival (DFS) vs placebo when used in the adjuvant treatment of patients with stage IB to IIIA non–small cell lung cancer (NSCLC) following surgical resection, meeting 1 of the dual primary end points of the phase 3 KEYNOTE-091 trial (EORTC-1416-LCG/ETOP-8-15-PEARLS; NCT02504372).1,2
Data from the trial, which were presented during the March 2022 ESMO Virtual Plenary, showed that the median DFS with the immunotherapy (n = 590) was 53.6 months (95% CI, 39.2–not reached [NR] vs 42.0 months (95% CI, 31.3-NR) with placebo (n = 587) in the overall population, translating to an improvement of almost 1 year (hazard ratio [HR], 0.76; 95% CI, 0.63-0.91; P = .0014).
“These are the first positive results for [pembrolizumab] in the adjuvant setting for NSCLC and represent the sixth positive pivotal study evaluating a [pembrolizumab]-based regimen in earlier stages of cancer,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, as well as chief medical officer at Merck Research Laboratories, stated in a press release. “[Pembrolizumab] has become foundational in the treatment of metastatic NSCLC, and we are pleased to present these data showing the potential of [pembrolizumab] to help more patients with lung cancer in earlier stages of disease.”
The triple-blind phase 3 trial enrolled patients with confirmed stage IB, II, or IIIA NSCLC who underwent complete surgical resection with negative margins and had tumor tissue available for PD-L1 testing.
To be eligible for randomization, patients needed to have an ECOG performance status of 0 or 1. Adjuvant chemotherapy could be considered for those with stage IB disease and was strongly recommended for those with stage II and IIIA disease but was limited to 4 cycles. Patients could not have evidence of disease.
Study participants were randomized 1:1 to receive pembrolizumab at 200 mg or placebo every 3 weeks for up to 18 administrations or approximately 1 year. Key stratification factors included disease stage (stage IB vs stage II vs stage IIIA), PD-L1 tumor proportion score (TPS; <1% vs 1%-49% vs ≥50%), receipt of adjuvant chemotherapy (yes vs no), and geographic region (Asia vs Eastern Europe vs Western Europe vs rest of the world).
The dual primary end points of the trial were DFS in the overall population and in the subset of patients with a PD-L1 TPS of 50% or higher. Key secondary end points included DFS in the subset of patients with a PD-L1 TPS of 1% or higher; overall survival (OS) in the overall population, the PD-L1 TPS of 50% or higher subset, and the PD-L1 TPS of 1% or higher subset; lung cancer–specific survival in the overall population; and safety.
The median age in both treatment arms was 65 years and the majority of patients in the investigative and control arms, respectively, were male (68.0% vs 68.7%), were from Western Europe (51.4% vs 51.3%), had nonsquamous histology (67.5% vs 61.8%), had stage II disease (55.8% vs 57.6%), and received adjuvant chemotherapy (85.8% vs 85.9%).
Moreover, 35.6% and 41.6% of patients on the investigative and control arms, respectively, had an ECOG performance status of 1; 6.6% and 5.8% of patients, respectively, had tumors harboring an EGFR mutation, and 1.2% of patients in both arms had tumors that harbored a ALK translocation. In the investigative arm, 39.5% of patients had a PD-L1 TPS of less than 1%, 32.0% had a TPS between 1% and 49%, and 28.5% had a TPS of 50% or higher; these rates were 39.5%, 32.4%, and 28.1%, respectively, in the control arm.
Previously, an improvement in DFS with pembrolizumab over placebo was observed in the subset of patients with a PD-L1 TPS of 50% or higher, although this benefit was not found to be statistically significant (HR, 0.82; 95% CI, 0.57-1.18; P = .14). In this subset, the median DFS had not yet been reached in either arm.
Moreover, a favorable trend in OS was with pembrolizumab vs placebo, regardless of PD-L1 expression, with a HR of 0.87 (95% CI, 0.67-1.15; P = .07). However, these data are immature and were not found to reach statistical significance at the time of this interim analysis.
The safety profile of the immunotherapy observed in this study was noted to be consistent with what has previously been reported with the agent.
Investigators will continue to examine DFS in the subset of patients with a PD-L1 TPS of 50% or higher, as well as to evaluate OS.
“While significant advances have been made in the treatment of metastatic NSCLC, there remains an unmet need for patients with earlier stages of this disease, as up to 43% of them will experience disease recurrence following surgery,” Luis Paz-Ares, MD, PhD, chair of the medical oncology department of the Hospital Universitario Doce de Octubre, stated in a press release. “The positive DFS observed in this study with the use of [pembrolizumab] in the adjuvant setting has the potential to have important implications for how we treat patients with stage IB to IIIA NSCLC.”