Adjuvant Pembrolizumab Improves DFS in Stage IB-IIIA Non-Small Cell Lung Cancer

Adjuvant treatment with pembrolizumab (Keytruda) significantly improved disease-free survival (DFS) in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) following surgical resection regardless of PD-L1 expression, according to a press release by Merck.¹

Results were from the phase 3 KEYNOTE-091 trial (EORTC-1416-LCG/ETOP-8-15 – PEARLS, NCT02504372) presented during the March 2022 ESMO Virtual Plenary. The study examined pembrolizumab as adjuvant treatment for this patient population.

Findings showed superior disease-free survival (DFS) outcomes with active therapy versus placebo, meeting one of the dual primary endpoints, as well as reduced risk of disease recurrence or death by 24% compared to placebo (HR, 0.76 ;95% CI, 0.63-0.91]; P =.0014). Additionally, median DFS was 53.6 months for pembrolizumab compared to 42.0 months for placebo.

“These are the first positive results for keytruda in the adjuvant setting for non-small cell lung cancer and represent the sixth positive pivotal study evaluating a Keytruda-based regimen in earlier stages of cancer,” Roy Baynes, MD, senior vice president and head of global clinical development, chief medical officer of Merck Research Laboratories said, in the press release. “Keytruda has become foundational in the treatment of metastatic non-small cell lung cancer, and we are pleased to present these data showing the potential of Keytruda to help more patients with lung cancer in earlier stages of disease. We thank the patients, their caregivers and investigators for participating in this study.”

Previous data from an interim analysis made available in January 2022 revealed that DFS in the PD-L1–positive cohort of the KEYNOTE-091 study, defined by having a tumor proportion score (TPS) ≥ 50%, improved with pembrolizumab.²

Within the PD-L1-positive population, data showed an 18% reduction in the risk of disease recurrence or death (HR, 0.82; 95% CI, 0.57-1.18; P =.14), and median DFS was not reached in either arm. In regard to a key secondary end point, a trend toward favorable overall survival (OS) in all patients, regardless of PD-L1 expression (HR, 0.87; 95% CI, 0.67-1.15; P =.17) was observed.

However, investigators noted that these data were not mature or statistically significant by the pre-specified statistical plan at the time of this interim analysis. These results allow for the continuation of the trial which will evaluate DFS in a population of patients with PD-L1 TPS of 50% or more and OS.

“We are encouraged by these new phase 3 data, as they represent the first-time adjuvant immunotherapy has demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with stage IB-IIIA non-small cell lung cancer,” said Professor Mary O'Brien, consultant medical oncologist, head of the Lung Unit at The Royal Marsden NHS Foundation Trust, professor, co-principal investigator of practice at Imperial College London.

The randomized clinical trial, KEYNOTE-091, which had a primary end point of DFS and secondary end points of OS and lung cancer specific survival, enrolled a total of 1177 patients with stage IB/II-IIIA NSCLC. Participants received either treatment with adjuvant pembrolizumab at 200 mg administered via intravenous infusion every 3 weeks or the matching placebo.³

Patients were eligible for enrollment if they had pathologically confirmed stage IB/II-IIIA NSCLC with an available tissue for biopsy, an ECOG performance score of 0-1, and adequate organ function. Females who were pregnant when enrolling were ineligible to participate in the trial and all patients must agree to use contraception while the study is ongoing.

In addition to KEYNOTE-091, there are 5 other pivotal trials currently evaluating pembrolizumab for use in patients with earlier stages. The trials, KEYNOTE-716 (NCT03553836) in stage IIB and IIC melanoma, KEYNOTE-054 (NCT02362594) in stage III melanoma, KEYNOTE-564 (NCT03142334) in renal cell carcinoma, KEYNOTE-522 (NCT03036488) in triple-negative breast cancer; and KEYNOTE-057 (NCT02625961) in Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer of cancer met their primary end point(s).

References:

1. Merck’s Keytruda (pembrolizumab) significantly improved disease-free survival (DFS) versus placebo as adjuvant therapy in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) regardless of PD-L1 expression. New release. Merck. March 17, 2022. Accessed March 21, 2022. https://bit.ly/3KRkJAY
2. 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 March 21, 2022. https://bit.ly/3GgGS9O
3. Study of pembrolizumab (MK-3475) vs placebo for participants with non-small cell lung cancer after resection with or without standard adjuvant therapy (MK-3475-091/KEYNOTE-091) (PEARLS). Clinicaltrials.gov. Accessed March 21, 2021. https://bit.ly/3HRAxlS