European Commission Approves Adjuvant Pembrolizumab for High-Risk NSCLC

The European Commission has approved pembrolizumab (Keytruda) as adjuvant monotherapy for the treatment of adult patients with non–small cell lung cancer (NSCLC) who are at high risk of recurrence following complete resection and platinum-based chemotherapy.¹

The approval was based on findings from the phase 3 KEYNOTE-091 trial (NCT02504372), in which pembrolizumab led to a clinically meaningful improvement in investigator-assessed disease-free survival (DFS) vs placebo in patients who received adjuvant chemotherapy at a median follow-up of 46.7 months (HR, 0.76; 95% CI, 0.64-0.91).

“In the unfortunate scenario that NSCLC recurs after surgery, most patients have to face limited palliative treatment strategies, underscoring the need to improve treatment outcomes for earlier stages of NSCLC,” Solange Peters, MD, PhD, chair of the medical oncology and thoracic malignancies department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, stated in the news release. “This approval of pembrolizumab marks the first immunotherapy option approved in the European Union for patients with NSCLC who are at high risk of disease recurrence following surgery and chemotherapy, regardless of PD-L1 expression.”

In January 2023, the FDA approved pembrolizumab as an adjuvant treatment following resection and platinum-based chemotherapy for patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.²

Previously, with a median follow-up of 32.4 months, pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in DFS vs placebo in the overall population of patients with stage IB (T2a ≥4cm), II, or IIIA NSCLC per the American Joint Committee on Cancer (AJCC) seventh edition staging criteria (HR, 0.76; 95% CI, 0.63-0.91; P = .0014).

At the time of FDA approval, median DFS was 58.7 months (95% CI, 39.2–not reached [NR]) with pembrolizumab vs 34.9 months (95% CI, 28.6-NR) with placebo in patients who had received adjuvant chemotherapy (HR, 0.73; 95% CI, 0.60-0.89). Findings from an exploratory analysis demonstrated that patients who did not receive adjuvant chemotherapy (n = 167; 14%) did not experience DFS benefit with pembrolizumab (HR, 1.25; 95% CI, 0.76-2.05).³

The study evaluated pembrolizumab vs placebo as adjuvant therapy for patients with NSCLC who were at high risk (stage IB [T2a ≥ 4cm], II, or IIIA disease per AJCC 7th edition staging criteria) of recurrence following complete resection, regardless of tumor PD-L1 expression status. Per the study design, adjuvant chemotherapy consisting of up to 4 cycles was optional, but neoadjuvant chemotherapy and radiotherapy were prohibited.¹

Regarding baseline characteristics, 1010 patients (86%) received adjuvant platinum-based chemotherapy after resection. Patients who received adjuvant chemotherapy had a median age of 64 years (range, 35-84); 49% were 65 years of age or older. Additionally, 68% of patients were male, 77% were White, and 18% were Asian. Most patients (86%) were current or former smokers, and 39% had an ECOG performance status of 1. Eleven percent of patients had stage IB disease, 57% had stage II disease, and 31% had stage IIIA disease. Thirty-nine percent of patients had a positive PD-L1 tumor proportion score (TPS).³

A total of 1,177 patients were randomly assigned 1:1 to receive 200 mg of intravenous (IV) pembrolizumab every 3 weeks for one year or a maximum 18 doses (n = 590) or IV placebo every 3 weeks for one year or a maximum 18 doses (n = 587). Patients received a median of 17 doses of pembrolizumab and a median of 18 doses of placebo.

The dual primary end points were DFS in the overall population and in patients with a PD-L1 TPS of at least 50%. Secondary end points included overall survival (OS). At the time of the news release, OS data were not mature, with only 58% of prespecified OS events having occurred in the overall population.¹

“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,” Gregory Lubiniecki, MD, vice president, global clinical development, Merck Research Laboratories, stated. “We are proud that in Europe, pembrolizumab now has five approved indications in NSCLC, in both earlier and advanced stages of disease.”

References

1. European Commission approves Keytruda (pembrolizumab) as adjuvant treatment for adults with non-small cell lung cancer at high risk of recurrence following complete resection and platinum-based chemotherapy. News release. Merck. October 16, 2023. Accessed October 16, 2023. https://www.merck.com/news/european-commission-approves-keytruda-pembrolizumab-as-adjuvant-treatment-for-adults-with-non-small-cell-lung-cancer-at-high-risk-of-recurrence-following-complete-resection-and-platinum-based/
2. FDA approves pembrolizumab as adjuvant treatment for non-small cell lung cancer. News release. FDA. January 26, 2023. Accessed October 16, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-non-small-cell-lung-cancer
3. Keytruda. Prescribing information. Merck; 2023. Accessed October 16, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125514s128lbl.pdf