Yi Long Wu, MD
Nivolumab (Opdivo) improved survival versus docetaxel in a predominantly Chinese population of patients with pretreated advanced or metastatic non–small cell lung cancer (NSCLC), according to Bristol-Myers Squibb (BMS), the manufacturer of the PD-1 inhibitor.
BMS announced that the phase III CheckMate-078 trial has been stopped early based on a recommendation from an independent panel, which concluded that the study had achieved its primary endpoint of improved overall survival (OS) with nivolumab versus docetaxel. According to BMS, this is the first phase III trial to demonstrated a survival benefit with an immuno-oncology agent in a Chinese population.
The company also reported that the China Food and Drug Administration has accepted a biologics license application for the use of nivolumab in patients with previously treated NSCLC. Data from the CheckMate-078 trial will be presented at a future medical meeting.
“It is exciting to see that the Phase 3 CheckMate-078 study met its primary endpoint early, which confirmed, for the first time, a superior overall survival benefit with a PD-1 inhibitor, nivolumab, in Chinese patients, compared with the standard treatment, docetaxel,” Yi-Long Wu, MD, a tenured professor of the Guangdong Lung Cancer Institute and the Guangdong General Hospital, chair of the Chinese Thoracic Oncology Group (CTONG) and the principal investigator of CheckMate-078, said in statement.
“Based on the topline results, nivolumab has the potential to become the first immuno-oncology treatment approved for previously treated lung cancer patients in China, and I hope that Chinese patients with NSCLC can benefit from this groundbreaking immuno-oncology treatment as early as possible,” added Wu.
The phase III CheckMate-078 trial accrued 504 patients with squamous or nonsquamous stage IIIb/IV NSCLC who progressed following platinum-based doublet chemotherapy. The study included 451 Chinese patients, 45 Russian patients, and 8 patients from Singapore.
Patients were randomized to 3 mg/kg of nivolumab intravenously every 2 weeks or docetaxel at 75 mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity. Beyond the primary OS endpoint, secondary endpoints included objective response rate, progression-free survival, time to treatment failure, efficacy across subgroups, rates of treatment-related adverse events (AEs), and rate of disease-related symptom deterioration measured by the lung cancer symptom scale. The AEs reported for the nivolumab arm were consistent with the safety profile for the PD-1 inhibitor from previous trials.
“The results of CheckMate -078 mark the third time Opdivo has demonstrated a survival advantage in previously treated metastatic non–small cell lung cancer. In China, where lung cancer is the leading cause of cancer death, these results are especially important, as they represent the first phase III trial to show an overall survival benefit with a PD-1 inhibitor in the Chinese patient population. Through our Opdivo clinical development program, we aim to bring the potential for long-term survival to patients where significant unmet medical needs remain,” Nick Botwood, MD, development lead, thoracic cancers, BMS, said in a press release.
In the United States, the FDA approved nivolumab in March 2015 for the treatment of patients with advanced squamous NSCLC who have progressed on or after platinum-based chemotherapy. The approval was based on data from the phase III CheckMate-017 trial, in which treatment with nivolumab improved OS by 41% versus docetaxel (9.2 vs 6.0 months; HR, 0.59; 95% CI, 0.44-0.79; P
In March 2015, the FDA approved nivolumab for patients with nonsquamous NSCLC who progress on or following platinum-based chemotherapy, or EGFR- or ALK-targeted agents in patients harboring those mutations, based on data from the phase III CheckMate-057 trial. Data from an interim analysis presented at the 2015 ASCO Annual Meeting showed a median OS of 12.2 months with nivolumab versus 9.4 months with docetaxel (HR, 0.73; 96% CI, 0.59-0.89; P
= .00155), with a 1-year OS of 50.5% versus 39.0%, respectively.