Merck & Co., the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP) announced results from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS.

The study found that adjuvant treatment with pembrolizumab significantly improved disease-free survival (DFS), one of the dual primary endpoints, reducing the risk of disease recurrence or death by 24% compared to placebo (hazard ratio [HR]=0.76 [95% CI, 0.63-0.91]; p=0.0014) in patients with stage IB (≥4 centimeters) to IIIA non-small cell lung cancer (NSCLC) following surgical resection regardless of PD-L1 expression.

Median DFS was 53.6 months for pembrolizumab versus 42.0 months for placebo, an improvement of nearly one year. These data are being presented today during a European Society for Medical Oncology (ESMO) Virtual Plenary and will be shared with regulatory authorities worldwide.

“These are the first positive results for pembrolizumab in the adjuvant setting for non-small cell lung cancer, and represent the sixth positive pivotal study evaluating a pembrolizumab-based regimen in earlier stages of cancer,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.

“Pembrolizumab 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 pembrolizumab 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.”

As previously announced, there was also an improvement in DFS for patients whose tumours express PD-L1 (tumour proportion score [TPS] ≥50%) treated with pembrolizumab compared to placebo, the other dual primary endpoint; these results did not reach statistical significance per the pre-specified statistical plan (HR=0.82 [95% CI, 0.57-1.18]; p=0.14).

Among these patients, median DFS was not reached in either arm. Additionally, a favourable trend in overall survival (OS), a key secondary endpoint, was observed for pembrolizumab versus placebo regardless of PD-L1 expression (HR=0.87 [95% CI, 0.67-1.15]; p=0.17); these OS data are not mature and did not reach statistical significance at the time of this interim analysis.

The trial will continue to evaluate DFS in patients whose tumours express high levels of PD-L1 (TPS ≥50%) and OS. The safety profile of pembrolizumab in this study was consistent with that observed in previously reported studies.

“Lung cancer is most treatable at earlier stages, and adding treatment after surgery may help reduce the risk of recurrence,” said Professor Mary O'Brien, consultant medical oncologist and head of the Lung Unit at The Royal Marsden NHS Foundation Trust and professor of practice (medical oncology) at Imperial College London, as well as co-principal investigator.

“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.”

“While significant advancements have been made in the treatment of metastatic non-small cell lung cancer, 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,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain and co-principal investigator.

“The positive disease-free survival data 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-IIIA non-small cell lung cancer.”

In addition to KEYNOTE-091, five other pivotal trials evaluating a pembrolizumab-based regimen in patients with earlier stages of cancer met their primary endpoint(s). These trials included: KEYNOTE-716 in stage IIB and IIC melanoma; KEYNOTE-054 in stage III melanoma; KEYNOTE-564 in renal cell carcinoma; KEYNOTE-522 in triple-negative breast cancer; and KEYNOTE-057 in Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle-invasive bladder cancer.

MSD has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations. Key studies in earlier stages of NSCLC include KEYNOTE-091, KEYNOTE-671, KEYNOTE-867 and KEYLYNK-012.

Source: European Organisation for Research and Treatment of Cancer