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Two parts of a phase I trial found that nivolumab could be a good first-line treatment option for patients with advanced non–small-cell lung cancer.
Two parts of a phase I trial found that nivolumab could be a good first-line treatment option for patients with advanced non–small-cell lung cancer (NSCLC). In one part of the study, the immunotherapy agent yielded good safety results and durable responses as monotherapy, and in the other, nivolumab combined with platinum-based doublet chemotherapy had more toxicity but again good responses.
Currently, platinum-based doublet chemotherapy (PT-DC) is the standard of care as a first-line therapy for NSCLC that is not driven by an EGFR or ALK mutation or rearrangement.
“Immune checkpoint inhibitors represent a distinct approach to treating malignancies, with durable antitumor activity and the potential for long-term survival demonstrated in multiple tumor types, including NSCLC,” wrote Scott Gettinger, MD, of Yale Cancer Center in New Haven, Connecticut, and co-authors of the monotherapy study.
CheckMate 012 was a multi-cohort phase I study designed to test nivolumab, a PD-1 inhibitor, as a first-line treatment in this malignancy. In the cohort reported by Gettinger’s group, 52 patients with advanced NSCLC were treated with nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. Both analyses were published online ahead of print today in the Journal of Clinical Oncology.
Adverse events of any grade occurred in 71% of that group, with fatigue (29%), rash (19%), and nausea (14%) among the most common. Ten patients (19%) had grade 3/4 adverse events, with rash being the only such event to occur in more than one patient (2.4%). Six patients discontinued nivolumab therapy because of an adverse event.
The confirmed objective response rate (ORR) was 23%; that included four patients with ongoing complete responses. Most of the responses (9 of 12) occurred early, by the first tumor assessment at week 11. The ORR was 28% in the 32 patients with PD-L1 expression on their tumor. At 24 weeks, the progression-free survival rate was 41%, and the median overall survival was 19.4 months.
“Nivolumab monotherapy as first-line therapy for patients with advanced NSCLC was generally well tolerated, showing promising activity with a manageable safety profile,” the authors concluded.
In the other study, led by Naiyer A. Rizvi, MD, of Columbia University Medical Center in New York, 56 patients received nivolumab along with a PT-DC regimen for 4 cycles, followed by nivolumab alone. There were no dose-limiting toxicities in the first 6 weeks of treatment.
In that cohort, grade 3/4 adverse events were more common, occurring in 45% of patients. Twelve patients (21%) discontinued therapy as a result of adverse events. The authors wrote that the safety profile was similar to that expected with single-agent therapy, though the discontinuation rate was higher with the combination therapy.
Again, there were promising response rates in this cohort. With paclitaxel/carboplatin along with nivolumab 5 mg/kg the ORR was 43%; with nivolumab 10 mg/kg and gemcitabine/cisplatin it was 33%; with nivolumab 10 mg/kg and pemetrexed/cisplatin it was 47%; and nivolumab 10 mg/kg with paclitaxel/carboplatin it was 47%.
The paclitaxel/carboplatin combination with nivolumab 5 mg/kg was deemed most promising, with a 2-year overall survival rate of 62% in those patients. With the other three combinations, the 2-year overall survival rates were 25%, 33%, and 27%, respectively.
“Our results suggest that the safety profile of nivolumab plus PT-DC can be managed using established safety guidelines,” the authors concluded. Both groups suggest that further randomized trials of nivolumab in this setting are warranted.