Pembrolizumab/Chemotherapy Approved by FDA in Resectable NSCLC
Those with resectable non–small cell lung cancer can now receive neoadjuvant treatment with pembrolizumab and chemotherapy followed by adjuvant pembrolizumab after approval by the FDA.
The News
The FDA has approved neoadjuvant pembrolizumab (Keytruda) plus chemotherapy plus continuation adjuvant pembrolizumab for patients with resectable non–small cell lung cancer.1
The indication includes patients with tumors 4 cm or greater or those who are node-positive. The approval was based on results from the phase 3 KEYNOTE-671 trial (NCT03425643).
The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks. Of note, pembrolizumab should be given prior to chemotherapy when given on the same day.
Phase 3 KEYNOTE-671 Data
Event-free survival (EFS) data from the KEYNOTE-671 study were previously presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.2,3 At the median follow-up of 25.2 months, investigators reported a reduction in disease recurrence, progression, or death of 42% (HR, 0.58; 95% CI, 0.46-0.72; P <.00001). The median EFS was not reached (NR) in the treatment arm (95% CI, 34.1-NR) compared with 17 months (95% CI, 14.3-22.0) in the placebo arm.
Data from a subgroup analysis highlighted an improvement in EFS regardless of PD-L1 expression. The pembrolizumab-based regimen reduced the risk of EFS events compared with placebo in those with a tumor proportion score (TPS) of 50% or more (HR, 0.42; 95% CI, 0.28-0.65), TPS between 1% and 49% (HR, 0.51; 95% CI, 0.34-0.75), and a TPS of less than 1% (HR, 0.77; 95% CI, 0.41-0.77).
The pembrolizumab-based regimen’s EFS benefit over placebo was observed in those with stage II (HR, 0.65; 95% CI, 0.42-1.01), stage III (HR, 0.54; 95% CI, 0.41-0.72), and stage IIIB disease (HR, 0.52; 95% CI, 0.31-0.88).
Investigators reported a reduction in EFS in patients who did (HR, 0.33; 95% CI, 0.09-1.22) and did not (HR, 0.69; 95% CI, 0.55-0.86) respond to treatment with perioperative pembrolizumab, according to findings from an exploratory analysis.
Data from a prespecified interim analysis indicated that the dual primary end point of overall survival (OS) was met in the pembrolizumab arm.3 Investigators have plans for a safety data read out at the upcoming 2023 European Society of Medical Oncology (ESMO) Congress.
Those with resectable stage II, IIIA, or IIIB non–small cell lung cancer can now receive treatment with pembrolizumab and chemotherapy following the combination’s FDA approval.
KEYNOTE-671 Trial Design
The KEYNOTE-671 trial evaluated neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab vs placebo plus neoadjuvant chemotherapy followed by adjuvant placebo. A total of 786 patients were enrolled on the trial. Those in the experimental arm received 200 mg of pembrolizumab intravenously (IV) every 3 weeks for 4 cycles plus 75 mg/m2 of IV cisplatin on day 1 of each cycle and either 1000 mg/m2 of IV gemcitabine on days 1 and 8 or 500 mg/m2 of IV pemetrexed on day 1. Patients then received adjuvant pembrolizumab at 200 mg IV every 3 weeks for up to 13 cycles. Patients could also receive a matched placebo in the control group in place of pembrolizumab.
The trial’s primary end points were EFS and OS. Key secondary end points included major pathological response rate, pathological complete response (pCR) rate, global health status/quality of life scores, and adverse effects.
Safety
The most common adverse effects (AEs) included nausea, fatigue, neutropenia, anemia, and constipation. For patients receiving neoadjuvant treatment, 6% were not able to receive surgery because AEs vs 4.3% in the placebo arm. Additionally, of the 3.1% of patients who received the neoadjuvant combination, surgery was delayed vs 2.5% in the placebo arm.
References
- FDA approves neoadjuvant/ adjuvant pembrolizumab for resectable non-small cell lung cancer. News release. FDA. October 16, 2023. Accessed October 17, 2023. https://bit.ly/3M3hfyi
- Wakelee HA, Liberman M, Kato T, et al. KEYNOTE-671: randomized, double-blind, phase 3 study of pembrolizumab or placebo plus platinum-based chemotherapy followed by resection and pembrolizumab or placebo for early stage NSCLC. J Clin Oncol. 2023;41 (suppl 17):LBA100. doi:10.1200/JCO.2023.41.17_suppl.LBA100
- Merck announces pivotal KEYNOTE-671 trial meets dual primary endpoint of overall survival (OS) in resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC). News release. October 10, 2023. Accessed October 10, 2023. https://bit.ly/48KrNMx
These data support less restrictive clinical trial eligibility criteria for those with metastatic NSCLC. This is especially true regarding both targeted therapy and immunotherapy treatment regimens.
