Pembrolizumab/Chemo Gets EU Recommendation in Resectable NSCLC

The FDA approved neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab for patients with resectable NSCLC in October 2023.

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of neoadjuvant pembrolizumab (Keytruda) plus chemotherapy followed by adjuvant pembrolizumab among patients with resectable non–small cell lung cancer (NSCLC), according to a press release from Merck, the developer of pembrolizumab.¹

The European Commission will now review the CHMP’s recommendation for approving the pembrolizumab-based combination, with a final decision anticipated in the first half of the 2024.

Supporting data for the CHMP’s recommendation came from the phase 3 KEYNOTE-671 trial (NCT03425643). In data published in The New England Journal of Medicine, the median event-free survival (EFS) was not reached (NR; 95% CI, 34.1-NR) with pembrolizumab plus chemotherapy compared with 17.0 months (95% CI, 14.3-22.0) with placebo plus chemotherapy (HR, 0.58; 95% CI, 0.46-0.72; P <.001).2 Additionally, the estimated 24-month EFS rates were 62.4% (95% CI, 56.8%-67.5%) vs 40.6% (95% CI, 34.8%-46.3%) in each respective arm.

The median overall survival (OS) was not NR (95% CI, NR-NR) in the pembrolizumab arm and 45.5 months (95% CI, 42.0-NR) in the placebo arm. At 24 months, the estimated OS rates were 80.9% (95% CI, 76.2%-84.7%) vs 77.6% (95% CI, 72.5%-81.9%) in each respective arm.

Overall, 44.9% of patients who received pembrolizumab plus chemotherapy and 37.3% of those who received placebo plus chemotherapy had grade 3 or higher treatment-related adverse effects (TRAEs). Investigators also reported serious TRAES in 17.7% and 14.3% of patients in each respective treatment arm. Common TRAEs in both arms included nausea, neutrophil count decreases, and anemia.

“The CHMP’s positive opinion puts us another step closer to helping certain patients in Europe with earlier stages of [NSCLC], regardless of PD-L1 expression,” Marjorie Green, MD, senior vice president and head of Oncology, Global Clinical Development at Merck Research Laboratories, stated in the press release.1 “We look forward to the European Commission’s decision, as we continue to build on the legacy of [pembrolizumab] in certain types of lung cancer and pursue meaningful advances that may help extend the lives of patients.”

Investigators of the double-blind KEYNOTE-671 trial randomly assigned 797 patients to receive pembrolizumab (n = 397) or placebo (n = 400) in combination with chemotherapy. Neoadjuvant treatment included intravenous pembrolizumab at 200 mg or matched placebo every 3 weeks for 4 cycles followed by cisplatin/gemcitabine or cisplatin/pemetrexed. Following surgery, patients received adjuvant pembrolizumab at 200 mg intravenously or placebo every 3 weeks for a maximum of 13 cycles.

The trial’s dual primary end points were investigator-assessed EFS per RECIST v1.1 criteria and OS. Key secondary end points included major pathological response (MPR), pathological complete response (pCR), and safety.

Patients 18 years and older with previously untreated and pathologically confirmed stage II, IIIA, or IIIB NSCLC considered to be resectable based on investigator assessment and surgical consultation were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1 and availability of a tumor sample for PD-L1 status assessment.

The pembrolizumab-based combination yielded MPRs in 30.2% (95% CI, 25.7%-35.0%) of patients compared with 11.0% (95% CI, 8.1%-14.5%) of those who received placebo plus chemotherapy (difference, 19.2 percentage points; 95% CI, 13.9%-24.7%; P <.0001; threshold, P = .0001). Additionally, a pCR was reported in 18.1% (95% CI, 14.5%-22.3%) and 4.0% (95% CI, 2.3%-6.4%) of each respective treatment arm, leading to a 14.2 difference in percentage points (95% CI, 10.1-18.7; P <.0001; threshold, P = .0001).

The FDA approved neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab for patients with resectable NSCLC in October 2023.3 The regulatory agency based its approval on the KEYNOTE-671 data.

References

1. Merck receives positive EU CHMP opinion for KEYTRUDA® (pembrolizumab) in combination with chemotherapy as neoadjuvant treatment, then continued as monotherapy as adjuvant treatment, for the treatment of resectable NSCLC at high risk of recurrence. News release. Merck. February 23, 2024. Accessed February 23, 2024. http://tinyurl.com/2cx5k39a
2. Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non–small cell lung cancer. N Engl J Med. 2023;389(6):491-503. doi:10.1056/NEJMoa2302983
3. FDA approves neoadjuvant/ adjuvant pembrolizumab for resectable non-small cell lung cancer. News release. FDA. October 16, 2023. Accessed February 23, 2024. https://bit.ly/3M3hfyi