Camrelizumab Plus Chemo Considered as New First-Line Therapy

The combination of camrelizumab and chemotherapy resulted in survival benefit for patients with metastatic or otherwise advanced non-squamous non–small-cell lung cancer (NSCLC), according to research to be presented on September 8, 2019, at the International Association for the Study of Lung Cancer 2019 World Conference on Lung Cancer held in Barcelona, Spain.

“Platinum-based chemotherapy remains first-line therapy for advanced NSCLC without oncogenic drivers in China,” according to authors, led by C. Zhou, Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai. “Camrelizumab (SHR-1210, a potent anti-PD-1 monoclonal antibody) has shown promising activity in multiple malignancies.”

In this phase III trial (n=419), 205 patients were randomized to receive camrelizumab along with chemotherapy and 207 patients were randomized to receive chemotherapy alone. Participants had metastatic or otherwise advanced non-squamous NSCLC without EGFR or ALK mutations. They were stratified according to sex and smoking history (≥400/year vs. <400/year).

Treatment was given every 3 weeks and patients were randomized 1:1 to receive 4-6 cycles of carboplatin and pemetrexed (500 mg/m2) plus or minus camrelizumab (200 mg), followed by pemetrexed plus or minus camrelizumab as maintenance therapy. Patients in the chemotherapy arm with disease progression were allowed to cross over to camrelizumab monotherapy.

The primary endpoint was progression-free survival (PFS), according to central review (RECIST v1.1). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and overall survival (OS).

Median follow-up time in the study was 11.9 months. In the camrelizumab plus chemotherapy group, median PFS was 11.3 months (95% CI,  9.5–not  reached) compared with that of 8.3 months (95% CI 6.0–9.7) in the chemotherapy alone group (HR 0.61 [95% CI 0.46–0.80], P=0.0002).

Clinical benefit of the camrelizumab-chemotherapy combination compared with chemotherapy alone was supported by all secondary outcomes and confirmed by independent review. Specifically, ORR was 60.0% (CI, 53.0–66.8; P<0.0001) vs 39.1% (CI, 32.4–46.1; P<0.0001). DCR was 87. 3% (CI, 82.0–91.6; P=0.0009) vs 74.4% (CI, 67.9–80.2; P=0.0009). DoR was 17.6 months (CI, 11.6–NR; P=0.0356) vs 9.9 months (CI, 8.5–13.8; P=0.0356) vs 20.9 months (14.2–not reached; P=0.0356) and OS was not reached (CI, 17.1–not reached; P=0.0272) vs 20.9 months (CI, 14.2–not reached; P=0.0272).

The rate of grade 3/4 adverse events was 66.8% in the camrelizumab plus chemotherapy arm vs 51.2% in the chemotherapy arm. Of note, 5 patients died secondary to treatment in the combination arm vs four deaths in the chemotherapy-alone arm.

 “First-line camrelizumab plus chemotherapy shows substantial clinical benefit in patients with advanced/metastatic non-squamous NSCLC with negative EGFR or ALK in terms of PFS, ORR, OS, and acceptable safety profiles,” concluded the authors. “The combination should become novel standard 1st line therapy for this population.”