Adding nintedanib to pemetrexed plus cisplatin prolonged progression-free survival (PFS) in patients with malignant pleural mesothelioma (MPM) and demonstrated a manageable toxicity profile, according to a study published in The Journal of Clinical Oncology.1
For this phase 2 study (ClinicalTrials.gov Identifier: NCT01907100), researchers randomly assigned 87 patients with unresectable, non-sarcomatoid MPM to receive 6 cycles of pemetrexed and cisplatin with nintedanib 200 mg twice daily or placebo, followed by nintedanib or placebo monotherapy. Patients were stratified by epithelioid or biphasic histology.
The primary analysis demonstrated that nintedanib prolonged PFS (hazard ratio [HR], 0.56; 95% CI, 0.34-0.91; P = .017), and these results were confirmed by updated PFS analyses (HR, 0.54; 95% CI, 0.33-0.87; P = .010).
Evidence from the study also trended towards improved overall survival (OS; HR, 0.77; 95% CI, 0.46-1.29; P = .319).
Patients with epithelioid histology experienced a median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30-0.82; P = .006; median [nintedanib vs placebo], 9.7 vs 5.7 months), and a median OS gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib vs placebo], 20.6 months vs 15.2 months).
The most frequently reported grade 3 or greater adverse event (AE) was neutropenia, occurring in 43.2% and 12.2% of nintedanib and placebo-receiving patients, respectively, and febrile neutropenia occurred in 4.5% of patients in the nintedanib arm. AEs led to discontinuation in 17.1% of patients in the placebo arm, and 6.8% of patients in the nintedanib arm.
The study authors noted that “the confirmatory phase 3 part of the study is ongoing.”
- Grosso F, Steele N, Novello S, et al. Nintedanib plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma: phase II results from the randomized, placebo-controlled LUME-Meso trial. J Clin Oncol. 2017 Sep 11. doi: 10.1200/JCO.2017.72.9012 [Epub ahead of print]