Nintedanib Boosts Malignant Pleural Mesothelioma PFS Achieved By Chemotherapy Alone

Adding nintedanib to first-line pemetrexed plus cisplatin chemotherapy extends progression-free survival for patients with unresectable malignant pleural mesothelioma

medwireNews: Phase II study findings show improved progression-free survival (PFS) with the angiokinase inhibitor nintedanib in patients undergoing pemetrexedcisplatin chemotherapy for treatment-naïve, unresectable, nonsarcomatoid malignant pleural mesothelioma.

Giorgio Scagliotti, from the University of Turin in Italy, and team report a “clinically meaningful benefit” for PFS among the 44 nintedanib-treated participants of the LUME-Meso trial. The hazard ratio (HR) was a significant 0.56 for the nintedanib group versus the 41 placebo-treated patients after 69 PFS events, later updated to 0.54 after 72 PFS events had occurred.

Overall survival (OS) also favoured the addition of nintedanib 200 mg twice daily over placebo to the chemotherapy regimen, with a HR of 0.77, although this did not reach statistical significance.

But when patients were stratified by histology, the HR for OS became significant for the subgroup of patients with epithelioid tumours who received nintedanib versus placebo, denoting a median OS gain of 5.4 months (20.6 vs 15.2 months, HR=0.70). PFS was also significantly longer in patients with epithelioid tumours who were given nintedanib compared with their placebo-treated counterparts (9.7 vs 5.7 months, HR=0.49).

With just 10 patients with biphasic histology, the number of patients was too low to provide a reliable estimate of treatment effect, the researchers comment.

“The median OS time of 20.6 months achieved in the epithelioid histology subtype is, to our knowledge, the longest reported in a randomized, double blind phase II study”, the authors write in the Journal of Clinical Oncology.

They add that “the median PFS prolongation of 4 months in these patients (with minimal additional toxicity) provided the rationale to proceed to the phase III component of the study.”

Grade 3 or more severe adverse events occurred in 79.5% of patients given chemotherapy plus nintedanib and 53.7% of those who received chemotherapy plus placebo, including an increase in the frequency of neutropenia in the nintedanib-treated patients (43.2 vs 12.2%).

Treatment was discontinued because of adverse events in 6.8% of the nintedanib-treated patients and 17.1% of controls, and 31.8% and 14.6% of patients required dose reduction of their study agent, respectively.

Reference

Grosso F, Steele N, Novello S, et al. Nintedanib plus pemetrexed/cisplatin in patients with malignant plural mesothelioma: Phase II results from the randomized, placebo-controlled LUME-Meso trial. J Clin Oncol; Advance online publication 11 September 2017. DOI: 10.1200/JCO.2017.72.9012

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