Nivolumab monotherapy demonstrates efficacy in previously treated NSCLC Gettinger SN, et al. J Clin Oncol. 2015;doi:10.1200/JCO.2014.58.3708.May 4, 2015 Nivolumab conferred durable responses and prolonged OS in patients with previously treated non–small cell lung cancer, according to study results. Nivolumab (Opdivo, Bristol-Myers Squibb) — a fully human immunoglobulin G4 programmed death 1 (PD-1) immune checkpoint inhibitor antibody — was well tolerated and active in patients with advanced NSCLC, melanoma and renal cell carcinoma in a phase 1 trial, according to the study background. Gettinger and colleagues evaluated data from 129 patients (median age, 65 years; 61% male) with advanced NSCLC. Patients were heavily pretreated — 54% had received three or more systemic treatments for their malignancy — and all patients experienced disease progression during treatment with at least one platinum- or taxane-based treatment regimen.Patients received 1- (n = 33), 3- (n = 37) or 10-mg/kg (n = 59) doses of nivolumab biweekly in 8-week cycles for up to 96 weeks.
Median follow-up was 39 months.Median OS was 9.9 months (95% CI, 7.8-12.4) across dose levels. Median OS for the 1-mg/kg and 10-mg/kg dose cohorts was 9.2 months; however, patients who received the 3-mg/kg dose (n = 37) — the dose chosen for investigation in phase 3 trials — achieved a median OS of 14.9 months (95% CI, 7.3-30.3).Across dose levels, the 1-year survival rate was 42% (95% CI, 33-50), 2-year survival rate was 24% (95% CI, 17-33) and 3-year survival rate was 18% (95% CI, 11-25).Fifty-six percent (95% CI, 38-71) of patients assigned the 3-mg/kg dose achieved 1-year OS, 42% (95% CI, 24-58) achieved 2 -year OS and 27% (95% CI, 12-43) achieved 3-year OS.
Median PFS for the entire population was 2.3 months (95% CI, 1.8-3.7).The objective response rate was 17% (n = 22), and the median response duration was 17 months (range, 1.4-36.8). Six additional patients displayed unconventional immune-pattern responses. Researchers noted median OS, survival rates and response rates were comparable in patients with squamous and nonsquamous NSCLC.A majority of patients (71%) experienced an adverse event of any grade, the most common of which were fatigue (24%), decreased appetite (12%) and diarrhea (10%). Grade 3 to grade 4 adverse events occurred in 14% of patients. Eighteen patients ceased treatment for reasons other than disease progression. Three patients died from treatment-related pneumonitis."Additional phase 1, 2 and 3 clinical trials are currently evaluating other anti-PD–1 or anti-PD–L1 antibodies and have shown encouragingly consistent activity in patients with advanced NSCLC," Gettinger and colleagues concluded. "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. Clinical trials evaluating combinations of nivolumab and other PD-1 axis inhibitors with chemotherapy, targeted therapy, epigenetic therapy and other immunotherapies are also underway or being planned and hold promise for fully realizing the potential of immunotherapy in NSCLC." – by Cameron Kelsall
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