Adding nintedanib to pemetrexed/cisplatin improved the progression-free survival of patients with malignant pleural mesothelioma compared with placebo.
Adding nintedanib to pemetrexed/cisplatin improved the progression-free survival (PFS) of patients with malignant pleural mesothelioma compared with placebo, according to updated results (abstract 8506) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.
Nintedanib is an oral multikinase inhibitor that targets vascular endothelial growth factor receptors 1–3, platelet-derived growth factor receptors Î±/Î², fibroblast growth factor receptors 1–3, and Src and Abl kinase signaling. Patients treated with nintedanib on this trial had a median PFS (the primary endpoint) gain of 3.7 months compared with placebo.
“This study met its primary endpoint and demonstrated clinical benefit in first-line treatment in patients with mesothelioma with the addition of nintedanib to pemetrexed and cisplatin,” said Anna K. Nowak, MD, of the University of Western Australia, who presented the results.
According to Nowak, mesothelioma is often diagnosed at an advanced stage. Pemetrexed/cisplatin is the only approved regimen for this disease, providing a median overall survival of about 1 year.
Data from the primary analysis of this trial showed that nintedanib improved PFS (hazard ratio [HR], 0.56; 95% CI, 0.34–0.91) compared with placebo. At the meeting, Nowak presented updated PFS and mature overall survival results.
The trial included 87 patients with unresectable mesothelioma who were randomly assigned to 6 cycles or less of pemetrexed/cisplatin plus nintedanib or placebo followed by nintedanib or placebo monotherapy until progression.
Results from the updated analysis showed a median PFS of 5.7 months for placebo compared with 9.4 months for nintedanib (HR, 0.54; 95% CI, 0.33–0.87; P = .010). In a preplanned subgroup analysis of patients with epithelioid histology, the median PFS increased from 5.7 months with placebo to 9.7 months with nintedanib (HR, 0.49; 95% CI, 0.30–0.82; P = .006).
There was no significant difference in overall survival between the two treatment arms (HR, 0.77; 95% CI, 0.46–1.29; P = .319). The median overall survival increased from 14.2 months in the placebo arm to 18.3 months in the nintedanib arm, but the difference was not statistically significant. In patients with epithelioid histology, the median overall survival was 20.6 months for nintedanib compared with 15.2 months for placebo (HR, 0.70; 95% CI, 0.40–1.21; P = .197).
Finally, the objective response rate was 57% in the nintedanib arm compared with 44% in the placebo arm (odds ratio, 1.66; 95% CI, 0.72–3.92).
There was substantially more neutropenia and thrombocytopenia in the nintedanib arm. In addition, diarrhea and abnormalities in liver function were also more common in the nintedanib arm. However, Nowak noted that few of the diarrhea events were grade 3 or higher. Four fatal serious adverse events occurred on the study-one in the nintedanib arm and three in the placebo arm-but all were related to disease progression.
A phase III study of this regimen is ongoing.