CHICAGO (FRONTLINE MEDICAL NEWS) – Adding the oral kinase inhibitor nintedanib to pemetrexed/cisplatin resulted in substantial improvements in outcomes in patients with unresectable malignant pleural mesothelioma in phase 2 of the randomized, placebo-controlled phase 2/3 LUME-Meso study.

The effects were particularly pronounced among those with epithelioid histology, Jose Barrueco, PhD, of Boehringer Ingelheim Pharmaceuticals, Ridgefield, Conn., reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Progression-free survival – the primary endpoint of the study – was improved in 44 patients randomized to receive up to six cycles of pemetrexed/cisplatin plus nintedanib, compared with 43 patients who received pemetrexed/cisplatin plus placebo (median 9.4 vs. 5.7 months; hazard ratio, 0.54), Dr. Barrueco said.

In the 89% of patients with epithelioid malignant pleural mesothelioma, progression-free survival was a median of 9.7 vs. 5.7 months with nintedanib vs. placebo (HR, 0.49).

There was a trend toward improved overall survival in the nintedanib group vs. the placebo group, (median 18.3 vs. 14.2 months; HR, 0.77; P = .319), and overall survival was slightly better in those with epithelioid histology (median 20.6 vs. 15.2 months ; HR, 0.70; P = .197).

Consistent with these results, the adjusted mean change in forced vital capacity at cycle eight also favored nintedanib over placebo (+10.0 vs. +2.8 for a mean treatment difference of 7.2 overall, and +14.1 vs. +4.2 for a mean treatment difference of 9.9 in those with epithelioid histology).

“Overall frequency of adverse events was consistent with the known safety profile of nintedanib,” Dr. Barrueco said, noting that most adverse events were reversible with dose reduction.

Study participants were chemotherapy-naive patients with a mean age of 67 years and Eastern Cooperative Oncology Group performance status of 0-1. They received pemetrexed at a dose of 500 mg/m2 and cisplatin at a dose of 75 mg/m2 on day 1 plus either nintedanib at a dose of 200 mg twice daily on days 2-21 or placebo, followed by monotherapy with nintedanib or placebo until progression or unacceptable toxicity.

“In conclusion, nintedanib plus pemetrexed/cisplatin demonstrated a signal for clinical benefit in the first-time treatment of patients with malignant pleural mesothelioma. This was evident in all endpoints of the trial, and consistently showed benefit for the nintedanib group,” Mr. Barrueco said, noting that phase 3 of the LUME-Meso study is now recruiting.