China’s National Medical Products Administration has approved the combination of pembrolizumab plus carboplatin and paclitaxel for the first-line treatment of patients with metastatic squamous non–small cell lung cancer.
Jonathan Cheng, MD
China’s National Medical Products Administration (NMPA) has approved the combination of pembrolizumab (Keytruda) plus carboplatin and paclitaxel for the first-line treatment of patients with metastatic squamous non—small cell lung cancer (NSCLC).1
The approval is based on interim overall survival (OS) findings from the phase III KEYNOTE-407 trial, as well as interim data that were part of an extension of the international study in Chinese patients. Results showed that the pembrolizumab/chemotherapy combination led to a 36% reduction in the risk of death compared with chemotherapy alone (HR, 0.64; 95% CI, 0.49-0.85; P = .0017).2 In Chinese patients, the immunotherapy regimen led to a 56% reduction in the risk of death versus chemotherapy alone (HR, 0.44; 95% CI, 0.24-0.81).3
“In KEYNOTE-407, Keytruda in combination with chemotherapy significantly improved both overall survival and progression-free survival in patients with metastatic squamous non—small cell lung cancer,” Ying Cheng, MD, director of Jilin Cancer Hospital, stated in a press release. “Lung cancer is the leading cause of cancer death in China, so this approval represents an important milestone for the patients and families facing this difficult-to-treat disease.”
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 (Abraxane) 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 survival (PFS) and OS; secondary endpoints included objective response rate (ORR) and duration of response (DOR).
Interim results also showed that pembrolizumab in combination with chemotherapy demonstrated an improvement in PFS, with a reduction in the risk of progression or death by 44% versus chemotherapy alone (HR, 0.56; 95% CI, 0.45-0.70; P <.0001). In the extension of the global study in Chinese patients, pembrolizumab/chemotherapy also demonstrated an improvement in PFS (HR, 0.32; 95% CI, 0.21-0.49).
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.
Final results of KEYNOTE-407 were presented during the 2019 ESMO Congress.4 At a median follow-up of 14.3 months (range, 0.1-31.3) the combination of pembrolizumab and chemotherapy continued to improve OS, with a median OS of 17.1 months versus 11.6 months for chemotherapy alone (HR, 0.71; 95% CI, 0.58-0.88). Additionally, the median PFS was 8.0 months versus 5.1 months, and the ORR was 62.6% and 38.4% with pembrolizumab/chemotherapy and chemotherapy alone, respectively.
Further final data showed that second-line therapy was received by 32.0% in the pembrolizumab and chemotherapy arm and 59.4% for those on chemotherapy alone. Moreover, PFS2 was longer for those who received frontline pembrolizumab/chemotherapy at a median 13.8 months versus 9.1 months for those who were on the chemotherapy-alone arm; PD-L1 tumor proportion score did not lead to differing outcomes.
“This approval expands our current lung cancer indications in China to include Keytruda in combination with chemotherapy in patients with squamous cell carcinoma, a particularly difficult-to-treat type of lung cancer,” Jonathan Cheng, MD, vice president, oncology clinical research, Merck Research Laboratories, the developer of the PD-1 inhibitor, stated in a press release. “Importantly, Keytruda provides a foundation for the treatment of lung cancer in China and now more patients with non-small cell lung cancer may have the opportunity to benefit from combination therapy with Keytruda.”
In October 2018, 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. The European Commission approved the combination in March 2019 for the same indication.