Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study.

PURPOSE: The objective was to determine the safety and clinical activity of atezolizumab (MPDL3280A), a humanized programmed death-ligand 1 (PD-L1) antibody, in renal cell carcinoma (RCC). Exploratory biomarkers were analyzed and associated with outcomes. PATIENTS AND METHODS: Seventy patients with metastatic RCC, including clear cell (ccRCC; n = 63) and non-clear cell (ncc; n = 7) histologies, received atezolizumab intravenously every 3 weeks. PD-L1 expression was scored at four diagnostic levels (0/1/2/3) that were based on PD-L1 staining on tumor cells and tumor-infiltrating immune cells (IC) with the SP142 assay. Primary end points were safety and toxicity; secondary end points assessed clinical activity per Response Evaluation Criteria in Solid Tumors version 1.1 and immune-related response criteria. Plasma and tissue were analyzed for potential biomarkers of atezolizumab response. RESULTS: Grade 3 treatment-related and immune-mediated adverse events occurred in 17% and 4% of patients, respectively, and there were no grade 4 or 5 events. Sixty-three patients with ccRCC were evaluable for overall survival (median, 28.9 months; 95% CI, 20.0 months to not reached) and progression-free survival (median, 5.6 months; 95% CI, 3.9 to 8.2 months), and 62 patients were evaluable for objective response rate (ORR; 15%; 95% CI, 7% to 26%). ORR was evaluated on the basis of PD-L1 IC expression (IC1/2/3: n = 33; 18%; 95% CI, 7% to 35%; and IC0: n = 22; 9%; 95% CI, 1% to 29%). The ORR for patients with Fuhrman grade 4 and/or sarcomatoid histology was 22% (n = 18; 95% CI, 6% to 48%). Decreases in circulating plasma markers and acute-phase proteins and an increased baseline effector T-cell-to-regulatory T-cell gene expression ratio correlated with response to atezolizumab. CONCLUSION: Atezolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with metastatic RCC. Correlative studies identified potential predictive and pharmacodynamic biomarkers. These results have guided ongoing studies and combinations with atezolizumab in RCC.

Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer.

OBJECTIVE: OCEANS is a randomized, placebo (PL)-controlled, phase 3 trial evaluating the efficacy and safety of bevacizumab combined with gemcitabine+carboplatin (GC) for patients with platinum-sensitive recurrent ovarian cancer (ROC). The study met its primary endpoint, demonstrating improved progression-free survival with GC+bevacizumab compared with GC+PL. Herein, we describe results of final overall survival (OS) and updated safety. METHODS: Patients with recurrent platinum-sensitive ROC (recurring ≥6months after first-line platinum-based therapy) and measurable disease at baseline were randomized to receive GC+bevacizumab or GC+PL for 6-10cycles; PL or bevacizumab was then continued until disease progression. In this updated analysis, a Cox proportional hazards model was used to compare OS between the 2 treatment arms. RESULTS: At the data cutoff date (July 19, 2013), 353 patients (72.9%) had died. Median follow-up for OS was 58.2months in the experimental arm and 56.4months in the control arm. Consistent with interim analyses, median OS was comparable between arms (GC+bevacizumab: 33.6months; GC+PL: 32.9months; hazard ratio=0.95; log-rank p=0.65), and was consistent across all examined patient subgroups. The frequency and severity of adverse events were consistent with previous analyses; no new safety concerns were identified. CONCLUSIONS: Results from final OS analysis of the phase 3 OCEANS study showed no significant difference in OS for patients treated with GC+bevacizumab compared with GC+PL.