Nivolumab Is China’s First Approved Immuno-Oncology Drug

A new era is being launched in China with the approval earlier this month of the country’s first immuno-oncology agent, nivolumab (Opdivo), for previously treated non–small-cell lung cancer (NSCLC). The China National Drug Administration approved nivolumab after a phase III study demonstrated it yielded superior overall survival (OS) compared with docetaxel in patients with previously treated NSCLC, regardless of PD-L1 expression and tumor histology.

Professor Yi-Long Wu, a tenured director of Guangdong General Hospital and the chair of the Chinese Thoracic Oncology Group, said lung cancer is a major public health issue in China and represents the highest incidence and mortality of all cancers in the country. “Opdivo prolongs a long-term survival for Chinese advanced lung cancer patients, especially for advanced squamous lung cancer that accounts for 30% to 40% [of cases],” Professor Wu told Cancer Network.

The approval is based on results of the phase III CheckMate -078 trial of nivolumab vs chemotherapy among patients with previously treated NSCLC. The findings were presented at the American Association for Cancer Research Annual Meeting in April 2018. CheckMate -078 was stopped early in November 2017 because the Independent Data Monitoring Committee concluded that nivolumab demonstrated superior OS compared with chemotherapy.

In CheckMate -078, nivolumab reduced the risk of death by 32% compared with chemotherapy, the primary endpoint (hazard ratio [HR], 0.68). Both the efficacy and safety of nivolumab in this patient population were consistent with the results of the landmark global CheckMate -017 and -057 studies. In CheckMate -078, grade 3/4 treatment-related adverse events (TRAEs) occurred less frequently with nivolumab than with docetaxel (10% vs 48%). Discontinuations due to grade 3/4 TRAEs were also less frequent with nivolumab (3%) compared with docetaxel (5%).

A phase III, multinational, randomized study, CheckMate -078 was conducted primarily in mainland China, with additional study sites in Hong Kong, Russia, and Singapore. The trial randomized 504 patients (451 from China, 45 from Russia, 8 from Singapore) without EGFR mutations and with both squamous and nonsquamous NSCLC, across programmed death ligand 1 (PD-L1) expression status of < 1% and ≥ 1%. All patients received either nivolumab at 3 mg/kg intravenously every 2 weeks (n = 338) or docetaxel 75 mg/m² intravenously every 3 weeks (n = 166) until documented disease progression or unacceptable toxicity.

Minimum follow-up was 8.8 months. Median OS was 12.0 months in the nivolumab arm and 9.6 months in the chemotherapy arm (HR, 0.68). Improved OS with nivolumab vs docetaxel was observed in patients with squamous (HR, 0.61) and nonsquamous (HR, 0.76) tumor histology, and across all predefined subgroups based on tumor PD-L1 expression level. The hazard ratios in patients with tumor PD-L1 expression ≥ 1% were 0.62 and 0.75 in patients with tumor PD-L1 expression < 1%. The overall response rate (ORR) was 17% with nivolumab vs 4% with docetaxel. Median duration of response was not reached in the nivolumab arm vs 5.3 months in the docetaxel arm. Nivolumab decreased risk of disease progression by 23% compared with docetaxel (HR, 0.77).

Professor Wu commented that most lung cancer patients already have advanced-stage disease when diagnosed, so prolonging survival is an important goal. He said this approval is a significant therapeutic advance and is welcome news for patients and clinicians in China.