The immune checkpoint inhibitor nivolumab generated encouraging response rates and overall survival rates in heavily pretreated patients with non–small cell lung cancer, according to a report published online April 20 in the Journal of Clinical Oncology.

In a phase I multicenter dose escalation trial evaluating nivolumab at 1, 3, and 10 mg/kg in 129 patients, the overall response rate (ORR) across all doses was 17.1% (95% CI, 11.0% to 24.7%), duration of response was 17.0 months (1.4+ to 36.8+), overall survival (OS) was 9.9 months (7.8 to 12.4), and 1-, 2-, and 3-year survival rates were 42%, 24%, and 18%, respectively.

At 3 mg/kg, the dose currently being used for phase III trials, ORR was 24.3% (11.8% to 41.2%), OS was 14.9 months (7.3 to 30.3), and 1-, 2-, and 3-year survival was 56%, 42%, and 27%, respectively.

The ORR in the subgroup of patients who had received three or more prior treatments was 21%, similar to the ORR for the entire population, reported Dr. Scott N. Gettinger of the Yale Cancer Center, New Haven, Conn., and associates (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.58.3708]).

“This differs from chemotherapy, where response rates decrease with subsequent lines of therapy. [Outcomes with nivolumab treatment] surpass expectations of second- and third-line chemotherapies, taking into account the caveats of a phase I dose-escalation/expansion trial design,” the researchers wrote.

Expectations for current second-line chemotherapies for advanced non–small cell lung cancer (NSCLC) are ORRs of 7% to 9%, median OS of about 8 months, and 1-year survival of about 30%.

Treatment-related adverse events of any grade occurred in 71% of patients, most commonly fatigue (24%), decreased appetite (12%), and diarrhea (10%). Grade 3-4 events occurred in 14% of patients, most commonly fatigue (3%). There were three treatment-related deaths, all due to pneumonitis. No clear relationship between pneumonitis occurrence and dose level or treatment duration was observed. Guidelines for early identification and management of pneumonitis are now in place.

Additional phase I, II, and III trials are underway to evaluate nivolumab as well as other therapeutic antibodies directed to the immune checkpoint receptor, programmed death 1 (PD-1), or its ligand (PD-L1). The trials have produced consistently encouraging results in patients with advanced NSCLC.

“Efforts are now focusing on evaluating potential predictive biomarkers, such as tumor expression of PD-L1, to select populations most likely to benefit from antibodies targeting the PD-1 axis,” wrote Dr. Gettinger and his associates.


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