Bristol-Myers Squibb Co, said the China National Drug Administration has approved Opdivo (nivolumab injection) for the treatment of locally advanced or metastatic non-small cell lung cancer after prior platinum-based chemotherapy in adult patients without EGFR or ALK genomic tumor aberrations.
This is China’s first and only PD-1 inhibitor and is the only immuno-oncology agent to demonstrate a survival benefit compared with chemotherapy, based on data from the pivotal phase III CheckMate -078 trial, in which 90 percent of the patients enrolled were Chinese.
The approval is based on results from the phase III CheckMate -078 trial of Opdivo vs. chemotherapy among patients with previously treated NSCLC, findings from which were presented at the American Association for Cancer Research Annual Meeting in April 2018.
In November 2017, the trial was stopped early because the independent Data Monitoring Committee concluded that Opdivo demonstrated superior overall survival compared with chemotherapy. The application later received priority review by the Center for Drug Evaluation in China.
In CheckMate -078, Opdivo reduced the risk of death by 32 percent versus chemotherapy, the primary endpoint (HR 0.68; 97.7% CI: 0.52 to 0.90; p=0.0006), in patients with previously treated NSCLC. Both efficacy and safety of Opdivo in this patient population were consistent with the results of the landmark global CheckMate -017 and -057 studies. In CheckMate -078, Grade III/IV treatment-related adverse events occurred less frequently with Opdivo versus docetaxel (10 percent vs. 48 percent). Discontinuations due to Grade III/IV TRAEs were also less frequent with Opdivo (3 percent) than with docetaxel (5 percent).
CheckMate -078 is a phase III, multinational, randomized study comparing Opdivo with docetaxel in the treatment of patients with Stage IIIb/IV NSCLC whose disease has progressed after platinum-based doublet chemotherapy.
The study was conducted primarily in 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 non-squamous NSCLC, across PD-L1 expression status of <1% and ≥1%, to receive either Opdivo 3 mg/kg intravenously every two weeks (N=338) or docetaxel 75 mg/m2 intravenously every three weeks (N=166) until documented disease progression or unacceptable toxicity.
The primary endpoint was overall survival, including OS consistency observed with the global CheckMate -017 and CheckMate -057 studies. Secondary endpoints included objective response rate, progression-free survival, time to treatment failure, efficacy across subgroups, rates of treatment-related adverse events, and rate of disease-related symptom deterioration, as measured by the Lung Cancer Symptom Scale.
Minimum follow-up was 8.8 months. Median OS was 12.0 months in the Opdivo arm and 9.6 months in the chemotherapy arm (HR 0.68; 95% CI: 0.52 to 0.90; p=0.0006). Improved OS with Opdivo versus docetaxel was observed in patients with squamous (HR 0.61; 95% CI: 0.42 to 0.89) and non-squamous (HR 0.76; 95% CI: 0.56 to 1.04) tumor histology, and across all pre-defined subgroups based on tumor PD-L1 expression level.
The hazard ratios in patients with tumor PD-L1 expression ≥1% and <1% were 0.62 (95% CI: 0.45 to 0.87) and 0.75 (95% CI: 0.52 to 1.09), respectively. The ORR was 17 percent with Opdivo versus 4 percent with docetaxel. Median duration of response was not reached in the Opdivo arm versus 5.3 months in the docetaxel arm. Opdivo decreased risk of disease progression by 23 percent versus docetaxel (HR 0.77; 95% CI: 0.62 to 0.95; p=0.0147).
