PL02.09 Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial

Abstract

been limited progress in the last two decades and outcomes remain poor with a median overall survival (OS) of w10 months. IMpower133 (NCT02763579), a global Phase 1/3, double-blind, randomized, placebo-controlled trial evaluated efficacy and safety of adding atezolizumab, a humanized monoclonal antiePD-L1 antibody, or placebo to 1L carboplatin and etoposide in ES-SCLC. Method: Patients with measurable (RECIST v1.1) ES-SCLC, ECOG performance status 0 or 1, who had not received prior systemic treatment for ES-SCLC were enrolled. PD-L1 immunohistochemical testing was not required. Patients were randomized 1:1 to receive four 21-day cycles of carboplatin (AUC 5 mg/mL/min IV, Day 1) plus etoposide (100 mg/m 2 IV, Days 1-3) with either atezolizumab (1200 mg IV, Day 1) or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or progressive disease per RECIST v1.1. Patients meeting predefined criteria could receive treatment beyond progression. Co-primary endpoints were OS and investigator-assessed progression-free survival (PFS). Adverse events (AEs) were graded per NCI-CTCAE v4.0. Blood-based tumor mutation burden (bTMB) was assessed using prespecified cutoffs of 16 vs. <16 and 10 vs. <10 mutations/Mb. Result: In total, 201 patients were randomized to the atezolizumab group, and 202 to the placebo group. Median follow-up was 13.9 months. Median OS was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio [HR] 0.70 [95% confidence interval (CI): 0.54, 0.91; P¼0.0069]). Median PFS was 5.2 months and 4.3 months, respectively (HR 0.77 [95% CI: 0.62, 0.96; P¼0.017]). OS and PFS benefits were consistent across key patient subgroups. Investigator-assessed confirmed objective response rates were 60.2% and 64.4% in the atezolizumab and placebo groups, respectively; median duration of response, 4.2 and 3.9 months. Exploratory analyses showed OS survival benefits in subgroups above and below prespecified bTMB cutoffs. Grade 3-4 treatment-related AEs were reported in 56.6% vs. 56.1% patients in atezolizumab vs. placebo groups, respectively; serious treatment-related AEs occurred in 22.7% and 18.9% patients, respectively. Conclusion: Addition of atezolizumab to carboplatin and etoposide provided a significant improvement in OS and PFS in 1L ES-SCLC in an all-comer patient population. No unexpected safety signals were identified. Atezolizumab plus carboplatin and etoposide may represent a new standard regimen for patients with untreated ES-SCLC.

MicroRNA-215-5p Treatment Suppresses Mesothelioma Progression via the MDM2-p53-Signaling Axis

“…More recently, several notable multi-institutional trials failed to establish superior efficacy of any new targeted drugs 3 against MPM, such as defactinib (Control of Mesothelioma with Maintenance Defactinib [COMMAND] trial) 4 or nintedanib (LUME-Meso trial). 5 In part, an incomplete understanding of the molecular mechanism(s) underlying MPM 6 contributes to this apparent chemotherapeutic plateau.…”

MicroRNA-206 suppresses mesothelioma progression via the Ras signaling axis

“…Recently, the LUME-Meso study did not meet the primary progression-free endpoint with the addition of nintedanib (anti-VEGFR 1-3, PDGFR a and b, and fibroblast growth factor receptors [FGFR] 1-3, plus Src and Abl kinases). 40 In an ongoing trial (NCT02863055), nintedanib is being investigated as maintenance therapy in patients with non-progressive disease after first-line chemotherapy. In addition, there are ongoing investigations of newer biosimilars, such as ramucirumab (anti-VEGFR2) in the phase II randomized, multi-center trial in a second-line setting (NCT03560973).…”