Data from the phase 3 KEYNOTE-091 trial supported the European Commission’s approval of pembrolizumab as an adjuvant treatment for adults with non–small cell lung cancer at high risk of recurrence following complete resection and platinum-based chemotherapy.
The European Commission has granted approval to the PD-1inhibitor pembrolizumab (Keytruda) as a monotherapy for the adjuvant treatment of adults with non–small cell lung cancer (NSCLC) who are at high risk of recurrence following complete resection and platinum-based chemotherapy, according to a news release from Merck, the developer of the drug.1
Supporting data for the European approval came from findings from the phase 3 KEYNOTE-091 trial (NCT02504372). At a median follow-up of 46.7 months, pembrolizumab in the adjuvant setting demonstrated a clinically meaningful improvement in disease-free survival (DFS) compared with placebo in patients who received adjuvant chemotherapy, reducing the risk of disease recurrence or death by 24% (HR, 0.76; 95% CI, 0.64-0.91). At an earlier follow-up of 32.4 months, pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in DFS in the overall population (HR, 0.76; 95% CI, 0.63-0.91; P=.0014) compared with placebo in patients with NSCLC who are at high risk of recurrence, defined as stage IB (T2a ≥4 centimeters).
“Today’s approval demonstrates our continued progress to help more patients living with certain types of lung cancer in Europe, treating them earlier in their disease when it may be the most impactful,” said Gregory Lubiniecki, MD, vice president, Global Clinical Development, Merck Research Laboratories. “We are proud that in Europe, KEYTRUDA now has five approved indications in non-small cell lung cancer, in both earlier and advanced stages of disease.”
In this randomized, triple-blind, phase 3 trial, 1177 patients were recruited from 196 medical centers in 29 countries.2 Eligible patients were aged 18 years or older, with completely resected, pathologically confirmed stage IB (tumors of ≥4 cm in diameter). Eligible participants were randomly assigned (1:1) to intravenously receive either 200 mg of pembrolizumab or a placebo every 3 weeks for 1 year (or maximum 18 doses). The median number of doses was 17 for pembrolizumab and 18 for placebo.
The primary endpoint for this study was DFS in the overall population and in the population with a PD-L1 tumor proportion score (TPS) of 50% or greater. Pembrolizumab significantly prolonged DFS compared with placebo in the overall population of patients with completely resected stage IB to IIIA NSCLC who may or may not have received adjuvant chemotherapy (up to 4 cycles). Data from a subgroup analysis published in the Journal of Clinical Oncology showed that pembrolizumab also improved DFS in patients who received 1 to 4 cycles of prior adjuvant chemo.3 An additional efficacy outcome was overall survival (OS). Data showed that OS results were not mature, with only 58% of prespecified OS events in the overall population.
Safety was assessed in all participants randomly assigned to treatment who received at least one dose of study treatment.
Frequent adverse effects associated with pembrolizumab include immune-meditated adverse reactions, such as effects in liver enzymes, creatinine, and thyroid functions, as well as a fluctuation in blood cortisol levels and infections. Pembrolizumab can also cause immune-meditated pneumonitis, specifically in patients who have received prior thoracic radiation, immune-mediated colitis, diarrhea, cytomegalovirus infection/reactivation, immune-mediated hepatitis, hepatic toxicity, adrenal insufficiency, hypophysitis, thyroid disorders, immune-mediated nephritis with renal dysfunction, diabetes, immune-mediated rash or dermatitis, and other immune-mediated reactions.
This decision marks the fifth approval for pembrolizumab in lung cancer in the European Union (EU). This approval allows marketing of this pembrolizumab regimen in all 27 EU member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland.
Based on these results, pembrolizumab was also approved for adjuvant treatment in this patient population by the FDA in January 2023.4