Luis Paz-Ares, MD
The European Commission has approved pembrolizumab (Keytruda) in combination with carboplatin and either paclitaxel or nab-paclitaxel (Abraxane) for the frontline treatment of patients with metastatic squamous non–small cell lung cancer (NSCLC).
The approval is based on findings from the phase III KEYNOTE-407 trial, in which pembrolizumab plus chemotherapy demonstrated a 36% reduction in the risk of death compared with chemotherapy alone, regardless of PD-L1 expression (HR, 0.64; 95% CI, 0.49-0.85; P
With this approval, the combination can now be marketed in all 28 European Union member states, plus Iceland, Lichtenstein and Norway, said Merck, the manufacturer of the PD-1 inhibitor, in a press release.
“In KEYNOTE-407, first-line treatment with Keytruda in combination with chemotherapy resulted in significant improvements in overall survival for patients with metastatic squamous non–small cell lung cancer, regardless of PD-L1 expression,” said Luis Paz-Ares, MD, chair of the Department of Medical Oncology, Hospital Universitario Doce de Octubre, in Madrid, Spain, in the press release. “Lung cancer is the leading cause of cancer death in Europe, so this approval marks an important milestone for the patients and families facing this difficult-to-treat type of lung cancer.”
In the multicenter, double-blind, placebo-controlled, phase III KEYNOTE-407 study, 559 patients were randomized 1:1 to receive pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel versus carboplatin/paclitaxel or carboplatin/nab-paclitaxel alone. In the experimental arm, patients received carboplatin at AUC 6 mg/mL/min on day 1 of each 21-day cycle for 4 cycles, paclitaxel at 200 mg/m2
on day 1 of each 21-day cycle for 4 cycles or nab-paclitaxel at 100 mg/m2
on days 1, 8, and 15 of each 21-day cycle for 4 cycles, followed by pembrolizumab at 200 mg intravenously every 3 weeks. Pembrolizumab was administered prior to chemotherapy on day 1.
In the chemotherapy arm, patients received placebo and carboplatin AUC 6 mg/mL/min on day 1 of each 21-day cycle for 4 cycles and paclitaxel 200 mg/m2
on day 1 of each 21-day cycle for 4 cycles or nab-paclitaxel 100 mg/m2
on days 1, 8, and 15 of each 21-day cycle for 4 cycles, followed by placebo every 3 weeks.
The coprimary endpoints were progression-free and overall survival (OS); secondary endpoints included objective response rate (ORR) and duration of response (DOR).
Results also showed that the combination of pembrolizumab with carboplatin and either paclitaxel or nab-paclitaxel significantly improved progression-free survival, with a reduction in the risk of progression or death of 44% versus chemotherapy alone (HR, 0.56; 95% CI, 0.45-0.70; P
<.0001). Among those who received the immunotherapy/chemotherapy regimen, the ORR was 58% (95% CI, 52-64) compared with 38% (95% CI, 33-44) for patients who were treated with chemotherapy alone (P
Additionally, the median DOR was 7.7 months (range, 1.1+ to 14.7+ months) for patients on the pembrolizumab arm versus 4.8 months (range, 1.3+ to 15.8+ months) for those who received chemotherapy alone.
Regarding safety, the pembrolizumab regimen has been evaluated in 791 patients with NSCLC receiving pembrolizumab at 200 mg, 2 mg/kg, or 10 mg/kg every 3 weeks, in clinical trials, said Merck in the press release. In this patient population, the most frequent adverse events (AEs) were nausea (49%), anemia (48%), fatigue (38%), constipation (34%), diarrhea (31%), neutropenia (29%), and decreased appetite (28%). Grade 3 to 5 AEs were reported in 67% for the pembrolizumab regimen and 66% for chemotherapy alone.
“Keytruda provides a foundation for the treatment of lung cancer in Europe, and this approval expands our first-line combination indications to include adults with metastatic squamous non-small cell lung cancer,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “This is a meaningful treatment advance as an anti–PD-1 combination therapy is now approved in Europe for this type of non–small cell lung cancer. With this approval, more patients with non–small cell lung cancer may have the opportunity to benefit from combination therapy with Keytruda.”
The FDA approved first-line pembrolizumab for use in combination with carboplatin and either paclitaxel or nab-paclitaxel for the treatment of patients with metastatic squamous NSCLC in October 2018.
- European Commission Approves Merck’s KEYTRUDA® (Pembrolizumab) in Combination with Chemotherapy for First-Line Treatment of Adults with Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC). Merck. Published March 14, 2019. https://bit.ly/2TFGZab. Accesses March 14, 2019.
- Paz-Ares LG, Luft A, Tafreshi A, et al. Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients (Pts) with metastatic squamous (Sq) non-small cell lung cancer (NSCLC). J Clin Oncol. 2018;36 (suppl; abstr 105). doi: doi: 10.1056/NEJMoa1810865.