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Immunotherapy Regimen for EGFR-Mutated Non–Small-Cell Lung Cancer
Despite high initial response rates, patients with epidermal growth factor receptor (EGFR)–mutated non–small-cell lung cancer (NSCLC) develop resistance to EGFR tyrosine kinase inhibitors (TKIs), and median progression-free survival (PFS) ranges from 9 to 19 months with first-line treatment. Upon progression, most patients receive chemotherapy. There has been interest in integrating immunotherapy into treatment, however, single-agent immunotherapy has minimal efficacy.
In the previously reported IMpower150 trial, the addition of the PDL1 inhibitor atezolizumab to the combination of bevacizumab, carboplatin, and paclitaxel improved PFS, including in a heterogeneous subset of patients with EGFR mutations and ALK translocations, all of whom had progression on prior targeted therapy (NEJM JW Oncol Hematol Sep 2018 and N Engl J Med 2018; 378:2288).
Now investigators report results of ORIENT-31, which investigated the combination of the anti-PD-1 antibody sintilimab, the bevacizumab biosimilar IBI305, and pemetrexed and cisplatin chemotherapy in patients with advanced nonsquamous NSCLC with EGFR mutations and progression after initial treatment with an EGFR TKI. In this industry-supported trial conducted in China, 444 patients were randomized to sintilimab and IBI305 plus chemotherapy, sintilimab plus chemotherapy, or chemotherapy alone.
At a median follow-up of 9.8 months, PFS, the primary endpoint, was significantly improved in the sintilimab-IBI305-chemotherapy group versus the chemotherapy-alone group (6.9 vs. 4.3 months; hazard ratio, 0.46; P<0.0001), as was objective response rate (44% vs. 25%) and median duration of response (8.3 vs. 7.0 months). The regimens were generally well tolerated, with no new safety signals.
This trial is important for patients with EGFR-mutant NSCLC. Immunotherapy has generally not proven effective for these patients, but when given along with bevacizumab and chemotherapy, it appears to be more beneficial. This may occur because of the immunomodulatory effects of vascular endothelial growth factor (VEGF) inhibitors: the reversal of VEGF-mediated immunosuppression by these agents may enhance the T-cell–mediated cancer-cell killing ability of checkpoint inhibitors. This study along with others investigating immunotherapy will help us refine the best treatment approach for patients with EGFR-mutant TKI-resistant NSCLC.
Lu S et al.
Title: Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): First interim results from a randomised, double-blind, multicentre, phase 3 trial.
Source: Lancet Oncol 2022 Sep ; [e-pub]. (Abstract/FREE Full Text)