Interim results from the phase 3 KEYNOTE-091 show promise for the use of pembrolizumab in patients with stage IB-IIIA non–small cell lung cancer treated in the adjuvant setting.
Adjuvant pembrolizumab (Keytruda) treatment in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) following surgical resection regardless of PD-L1 expression has demonstrated improvement in disease-free survival (DFS) compared with placebo, meeting the primary end point of the phase 3 KEYNOTE-091, Merck announced in a press release.1
“Globally, lung cancer is the leading cause of cancer death and it remains critically important to detect and treat lung cancer early,” said Luis Paz-Ares, MD, PhD, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain, and co-principal investigator, in a press release. “The goal of adjuvant treatment is to lower the risk of cancer returning after surgery. By moving Keytruda 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-IIIA non-small cell lung cancer.”
Results were from an interim analysis of the randomized clinical trial (EORTC-1416-LCG/ETOP-8-15 – PEARLS, NCT02504372). The improvement in DFS observed with adjuvant pembrolizumab was statistically significant and clinically meaningful in the stage IB-IIIA NSCLC patient population. Further adjuvant pembrolizumab showed improvement in DFS versus placebo in the subgroup of patients whose tumors express PD-L1 with tumor proportion score (TPS) ≥ 50%. However, this result was not statistically significant.
The safety of adjuvant pembrolizumab observed at the interim analysis was consistent with what has been seen in prior studies.
“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,” said Professor Mary O’Brien, PhD, The Royal Marsden, NHS Foundation Trust, and Imperial College, London, UK and co-principal investigator, in the press release. “Data from KEYNOTE-091 suggest adjuvant Keytruda 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.”
In addition to DFS, the study is also evaluating overall survival and lung cancer-specific survival as secondary end points. A total of 1177 patients with stage IB/II-IIIA NSCLC will be assessed on treatment with adjuvant pembrolizumab 200 mg administered via intravenous infusion every 3 weeks or matching placebo.2
Patients with pathologically confirmed stage IB/II-IIIA NSCLC who have available tissue for biopsy, an ECOG performance score of 0-1, and adequate organ function are eligible to enroll. Females cannot be pregnant when enrolling in the trial and all patients must agree to use contraception while the study is ongoing.
Those ineligible to enroll are patients who have had more than 4 cycles of adjuvant therapy, prior anti-PD-1, anti-PD ligand-1/2, anti-CD137, or cytotoxic T-lymphocyte-associated protein 4, a live vaccine within 30 days prior to starting study treatment, were treated with an investigational agent or device within 4 weeks of study enrollment, had chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the last 3 days prior enrolling in the study, or had previous allogeneic transplant.
Comorbidities including Human Immunodeficiency Virus, active Hepatitis B or C, active autoimmune disease requiring systemic treatment within the last 2 years also make certain patients ineligible to participate in the study. Further, those with a history of a hematologic or primary solid tumor malignancy, active infection requiring therapy, or have toxicities above a grade 1 because of surgery of chemotherapy are ineligible.
Analyses are ongoing in KEYNOTE-091 and results will be presented at an upcoming medical meeting and shared with regulatory bodies.
“Keytruda has become foundational in the treatment of metastatic non-small cell lung cancer and we continue to advance research to explore its potential to help fight cancer earlier,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in the press release.1 “We are encouraged by these results supporting the potential role of Keytruda in stage IB-IIIA non-small cell lung cancer. We thank the patients, investigators, and our partners at EORTC and ETOP for their important contributions to this study and look forward to sharing these results with the medical community as soon as possible.”
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, 2022. Accessed January 10, 2022. https://bit.ly/3GgGS9O
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. Accessed January 10, 2021. https://bit.ly/3HRAxlS