Adjuvant Pembrolizumab Improves DFS in Stage IB-IIIA NSCLC, Irrespective of PD-L1 Expression

Roy Baynes, MD, PhD

Adjuvant treatment with pembrolizumab (Keytruda) led to a statistically significant and clinically meaningful improvement in disease-free survival (DFS) vs placebo in patients with stage IB to IIIA non–small cell lung cancer (NSCLC) following resection, regardless of PD-L1 expression, meeting 1 of the dual primary end points of the phase 3 KEYNOTE-091 trial (EORTC-1416-LCG/ETOP-8-15-PEARLS; NCT02504372).¹

Additional results from the interim analysis showed that pembrolizumab also resulted in an improved DFS compared with placebo in those whose tumors did express PD-L1 with a tumor proportion score (TPS) of 50% or higher; however, this was not found to meet statistical significance per the prespecified statistical plan for the trial.

Investigators will continue to examine DFS in patients with PD-L1–high tumors and will also evaluate the difference in overall survival (OS) between the 2 approaches, as a secondary end point.

KEYNOTE-091 is the first positive study for adjuvant pembrolizumab in patients with stage IB to IIIA NSCLC, according to Merck. Data from the trial are anticipated to read out at an upcoming medical conference, and to also be submitted to regulatory authorities for further discussion.

“[Pembrolizumab] has become foundational in the treatment of metastatic NSCLC and we continue to advance research to explore its potential to help fight cancer earlier,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, as well as chief medical officer of Merck Research Laboratories, stated in a press release. “We are encouraged by these results supporting the potential role of [pembrolizumab] in stage IB to IIIA NSCLC.”

KEYNOTE-091 enrolled patients with a pathological diagnosis of NSCLC that was Union for International Cancer Control v7 stage IB, II to IIIA following complete resection with margins that proved to be microscopically free of disease.² Patients had to have an ECOG performance status of 0 or 1 and acceptable organ function.

They could not have severe comorbidities, nor prior or planned neoadjuvant or adjuvant radiotherapy and/or neoadjuvant chemotherapy for their current malignancy. Patients also needed to have a tumor sample obtained at the time of resection to undergo assessment for PD-L1 expression per immunohistochemistry.

If patients had evidence of disease at the time of examination and/or baseline radiological assessment, received more than 4 cycles of adjuvant treatment, or received prior PD-1, PD-1/2, anti-CD137, CTLA-4 modulators, or other immune-modulating drugs, they were excluded.

Other exclusion criteria included having received a live vaccine within 30 days before their first infusion, having a history of human immunodeficiency virus, chronic use of immunosuppressive agents, a history of interstitial lung disease, active autoimmune disease that requires systemic treatment in the past 2 years, and a history of a hematologic or primary solid tumor, among others.

The trial enrolled a total of 1177 patients who were randomized 1:1 to receive either intravenous (IV) pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or IV placebo every 3 weeks for 1 year.

The dual primary end points are DFS in. the overall patient population and in those with a PD-L1 TPS of 50% or higher. Key secondary end points include OS and lung-cancer–specific survival.

“Surgery is widely considered the first and most important intervention for most patients with early-stage NSCLC; however, an estimated 43% of those who undergo surgery will see their disease return,” Professor Mary O’Brien, The Royal Marsden, National Health Service Foundation Trust, and Imperial College, London, United Kingdom, and co-principal investigator of KEYNOTE-091, added in the release. “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 to IIIA NSCLC.”

References

1. 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, 2021. Accessed January 10, 2022. https://bit.ly/3zJssg7
2. 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. Updated July 17, 2020. Accessed January 10, 2022. https://www.clinicaltrials.gov/ct2/show/NCT02504372