CHICAGO — The addition of nintedanib to pemetrexed/cisplatin appeared safe and effective for the treatment of patients with malignant pleural mesothelioma, according to results from the LUME-Meso trial presented at International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology.
Nintedanib (Ofev, Boehringer Ingelheim) is an intracellular inhibitor that targets multiple tyrosine kinases, including VEGFR 1–3, PDGFR /, FGFR 1–3, Src and Abl.
“Nintedanib strongly inhibits malignant pleural mesothelioma tumor growth in human xenograft models and reduces the colony-forming capacity and migratory activity of malignant pleural mesothelioma cell lines,” José Barrueco, executive director of global clinical development of oncology at Boehringer Ingelheim, said during the presentation.
Barrueco and colleagues conducted the phase 2/phase 3 double-blind, randomized LUME-Meso trial to evaluate the combination of nintedanib plus pemetrexed/cisplatin in chemotherapy-naive patients with unresectable malignant pleural mesothelioma.
The researchers randomly assigned 87 patients 1:1 to receive six cycles or more of 200 mg nintedanib twice daily (n = 44) or placebo (n = 43) in combination with 500 mg/m2 pemetrexed plus 75 mg/m2 cisplatin on day 1 of each cycle until disease progression or unacceptable toxicity.
PFS served as the primary endpoint. Secondary endpoints included OS and forced vital capacity, a common pulmonary function test reflecting patient performance and quality of life.
In the phase 2 portion of the trial, patients treated with nintedanib demonstrated improved PFS and a trend for prolonged OS.
At the primary OS analysis — which occurred after 71% of events — the nintedanib arm showed a trend toward a survival benefit (HR = 0.77; 95% CI, 0.46-1.29) compared with the placebo arm. Further, researchers confirmed the primary PFS results (HR = 0.54; 95% CI, 0.33-0.87).
Patients with epithelioid malignant pleural mesothelioma experienced the greatest benefit from nintedanib treatment for both PFS (9.7 months vs. 5.7 months; HR = 0.49; 95% CI, 0.3-0.82) and OS (20.6 months vs. 15.2 months; HR = 0.7; 95% CI, 0.4-1.21)
Nintedanib also appeared associated with greater improvement in adjusted mean forced vital capacity change from baseline to cycle 8 for all patients (+10 vs. +2.8; mean treatment difference, 7.2) and those with epithelioid histology (+14.1 vs. +4.2; mean treatment difference, 9.9).
The researchers noted a trend toward improved forced vital capacity associated with nintedanib from cycle 2 in all patients and among those with epithelioid histology.
The most common severe adverse event was neutropenia (43% vs. 12%).
“The safety profile was manageable and consistent with previous nintedanib studies, and it did not compromise delivery of the backbone chemotherapy,” Barrueco said.
Only 6.8% of adverse events in patients treated with nintedanib led to treatment discontinuation.
Barrueco noted the phase 3 portion of the LUME-Meso trial is currently recruiting patients with unresectable epithelioid malignant pleural mesothelioma. – by Kristie L. Kahl
Novello S, et al. Abstract OA03.06. Presented at: International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology; Sept. 14-16, 2017; Chicago.
Barrueco reports an employment role with Boehringer Ingelheim.