CHICAGO – Nivolumab monotherapy resulted in a median overall survival of 8.2 months and a 1-year survival rate of 41% in advanced, heavily pretreated squamous cell non–small cell lung cancer in a phase II study.
Advanced, treatment-refractory squamous cell non–small cell lung cancer (NSCLC) is an area of high unmet need with no effective therapeutic options and this cohort was “truly” treatment refractory, study author Dr. Suresh Ramalingam said at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.
Of the 117 patients, 65% had received at least three prior systemic regimens, 61% had progressive disease as their best response to the most recent therapy, and 76% came into the study within 3 months of completing their most recent therapy.
The patients had stage IIIB/IV disease and were given nivolumab 3 mg/kg IV every 2 weeks until progressive disease or unacceptable toxicity. Their median age was 65 years (range 37-87 years).
The study’s primary end point of objective response rate by independent radiology review was 15% (17/117 patients), including eight confirmed partial responses in patients with rapid progression on prior therapy, Dr. Ramalingam, director of medical oncology and the lung cancer program, Winship Cancer Institute of Emory University, Atlanta, said.
The median duration of response has not been reached and 76% of responses are ongoing. In all, 24% of patients received subsequent therapy, excluding subsequent immunotherapy.
Median progression-free survival (PFS) was 2 months and the 1-year PFS rate was 20%, he said.
An exploratory biomarker analysis of 76 evaluable samples showed nivolumab was clinically active in patients whose tumors were positive as well as negative for programmed death-ligand 1 expression.
Dr. Ramalingam highlighted a 73-year-old former smoker with stage IIIB disease and active brain metastasis at study entry who had stable disease after treatment with nivolumab that was ongoing at 68 weeks including a response in his brain lesions, despite having no prior central nervous system-directed therapy, and failing prior radiotherapy and three prior systemic regimens (cisplatin[Platinol]/gemcitabine [Gemzar], docetaxel [Taxotere], and vinorelbine [Navelbine]).
Overall, nivolumab was well tolerated, as shown by the fact that 85% of patients received at least 90% of their planned dose intensity, he said.
The safety profile was consistent with prior nivolumab studies, with 12% of patients discontinuing treatment because of toxicity. Two treatment-related deaths (one hypoxic pneumonia and one ischemic stroke) occurred in patients with multiple comorbidities and concurrent progressive disease.
A poster also presented at the meeting (Ab. 170, Gettinger, S.N., et al.) showed an objective response rate of 17% among 54 treatment-refractory patients given second-line or later nivolumab 1 mg/kg, 3 mg/kg, or 10 mg/kg every 2 weeks for squamous cell NSCLC, among other solid tumors. The median PFS was 3.8 months, 1-year PFS 27%, median overall survival 9.2 months, and 1-year overall survival 41%.
A phase III trial is also ongoing comparing overall survival of nivolumab vs. docetaxel in advanced squamous cell NSCLC after failure of prior platinum-based chemotherapy, Dr. Ramalingam said.