Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Another KRAS G12C inhibitor. Congrats to FCS Director of Drug Development Manish Patel, MD, one of the authors. Durable responses with less adverse events.
The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non–small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned.
Patients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method.
Seven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months [all patients]; 61.6 months [censored patients]), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5 v 29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9 v 5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS.
These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.
Another KRAS G12C inhibitor. Congrats to FCS Director of Drug Development Manish Patel, MD, one of the authors. Durable responses with less adverse events.
Neoadjuvant chemotherapy trial with post op nivolumab for 6 months shows promising results.
Patients with poor performance status do better on atezolizumab monotherapy vs. single agent chemotherapy.
Targeted therapy in NSCLC, FCS was part of this trial.
The NADIM-II study looked at perioperative Nivo+chemo vs. chemo alone in stIIIA – stIIIB NSCLC. High pCR rates with chemoIO are again seen, as in the Checkmate 816 and NADIM-I study, they were even higher in this cohort (37%), suggesting higher-stage patients derive the biggest benefit from neoadjuvant chemoIO. Pretty impressive results, however, I still must point out that this was a phase II study with a small sample size, OS benefits have not been demonstrated and this has yet to make it on to NCCN.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
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