Pembrolizumab Yields Significantly Improved Disease-Free Survival in Non–Small Cell Lung Cancer

Patients with stage IB to IIIA non–small cell lung cancer (NSCLC) who were treated with pembrolizumab (Keytruda) following surgical resection vs placebo experienced a statistically significant improvement in disease-free survival (DFS) regardless of PD-L1 expression, according to findings from an interim analysis of the phase 3 KEYNOTE-091 (NCT02504372) trial. 

Investigators reported an improvement in DFS among patients in the pembrolizumab cohort who expressed PD-L1 and had a tumor proportion score of 50% or higher. However, investigators noted that the study's dual primary end points did not meet statistical significance by the pre-specified statistical plan. Moving forward, investigators will continue to analyze DFS in this population in addition to overall survival. There were no new safety findings in this trial, as it aligned with other effects seen in previous studies.

The full results will be presented at an upcoming meeting and submitted to regulatory authorities.

“Surgery is widely considered the first and most important intervention for most patients with early-stage non-small cell lung cancer; however, an estimated 43% of those who undergo surgery will see their disease return. Data from KEYNOTE-091 suggest adjuvant [pembrolizumab] reduced the risk of disease recurrence or death after surgery in the overall population of patients with stage IB-IIIA non–small cell lung cancer,” co-principal investigator Mary O’Brien, MD, FRCP, consultant medical oncologist at The Royal Marsden, NHS Foundation Trust, and professor at Imperial College, London, UK and.

In this trial, 1177 patients were enrolled on the study and were randomized 1:1 to receive treatment with either intravenous pembrolizumab at 200 mg every 3 weeks for 1 year or the placebo every 3 weeks for 1 year. An additional secondary end point investigators will look at is lung cancer specific survival up to approximately 111 months.

Eligibility criteria for the trial included a pathological diagnosis of NSCLC confirmed via surgery or histology, available tumor sample from resection for PD-L1 immunohistochemistry expression assessment, and an ECOG performance status of 0 or 1. Exclusion criteria included evidence of disease at clinical examination or baseline, more than 4 cycles of adjuvant therapy, and treatment with anti–PD-L1, anti-PD ligant-1/2, anti-CD137, or cytotoxic T-lymphocyte–associated protein modulators.

“Globally, lung cancer is the leading cause of cancer death, and it remains critically important to detect and treat lung cancer early. The goal of adjuvant treatment is to lower the risk of cancer returning after surgery. By moving [pembrolizumab] into earlier stages of non–small cell lung cancer, we may be able to reduce the risk of disease recurrence after surgery for patients with stage IB to IIIA non–small cell lung cancer,” co-principal investigator Luis Paz-Ares, MD, chair of the medical oncology department at the Hospital Universitario Doce de Octubre, Madrid, Spain, concluded.

Reference

Merck’s Keytruda (pembrolizumab) showed statistically significant improvement in disease-free survival versus placebo as adjuvant treatment for patients with stage IB-IIIA non–small cell lung cancer regardless of PD-L1 expression. News Release. Merck. January 10, 2022. Accessed January 10, 2022. https://bit.ly/33ffKtk