Anna K. Nowak, PhD, MBBS
Frontline treatment with nintedanib plus pemetrexed and cisplatin improved progression-free survival (PFS) by 3.7 months for chemotherapy-naive patients with malignant pleural mesothelioma (MPM), according to data reported at the 2017 ASCO Annual Meeting.
In the phase II trial, known as LUME-Meso, the median PFS was 9.4 months with the nintedanib combination versus 5.7 months with pemetrexed and cisplatin alone (HR, 0.54; 95% CI, 0.33-0.87; P = .010). The median overall survival (OS) was 18.3 months with nintedanib versus 14.2 months with chemotherapy alone; however, this finding was not statistically significant (HR, 0.77; 95% CI, 0.46-1.29; P
Outcomes with nintedanib seemed more promising for patients with epithelioid MPM, which is the only histology being included in an ongoing phase III study exploring the triplet. In those with epithelioid MPM, the median OS was 20.6 versus 15.2 months; however, this improvement was also not statistically significant (HR, 0.70; 95% CI, 0.40-1.21; P
= .197). The median PFS in this population was 9.7 months with nintedanib versus 5.7 months with chemotherapy alone (HR, 0.49; 0.30-0.82; P
"Nintedanib plus pemetrexed and cisplatin demonstrated clinical benefit in first-line treatment of patients with MPM. The greatest benefit was observed in patients with epithelioid histology," said lead investigator Anna K. Nowak, PhD, MBBS, of the University of Western Australia, Perth. "The safety profile was manageable and consistent with previous nintedanib studies, and the nintedanib did not compromise delivery of the backbone chemotherapy."
The study randomized 87 patients to receive pemetrexed plus cisplatin with either placebo (n = 43) or nintedanib (n = 44). Nintedanib was administered at 200 mg twice daily for day 2 to 21. Pemetrexed was given at 500 mg/m2 and cisplatin was administered at 75 mg/m2
every 21 days. The primary endpoint of the study was PFS, with secondary outcomes focused on OS and ORR.
The median age of patients was 68 years in the nintedanib arm and 66 years in the placebo group. Approximately three-fourth of patients were male and the ECOG performance status was 0 and 1. Most patients had epithelioid histology (88%) and 80% had stage III/IV disease. A minority had received prior surgery (range, 4.7% to 11.4%). Time since diagnosis was 1.5 and 1.7 months, in the nintedanib and placebo groups, respectively.
The objective response rate (ORR) was 57% with nintedanib and 44% with chemotherapy (odds ratio, 1.66; 95% CI, 0.72-3.92). The median duration of response was 6.0 months in the nintedanib arm and 4.0 months for chemotherapy.
Following the study, 59.1% of patients in the nintedanib arm received systemic therapy compared with 67.4% in the placebo arm. In addition to chemotherapy, 11.4% and 14.0% of patients received subsequent immunotherapy, in the nintedanib and placebo groups, respectively.
The most common grade ≥3 adverse events (AEs) with nintedanib versus placebo were neutropenia (43.2% vs 12.2%) followed by liver-related investigations, increased GGT, increased ALT, and electrolyte imbalance. Febrile neutropenia was experienced by 2.3% of patients in the nintedanib arm compared with none of those in the placebo group. AEs leading to discontinuation were experienced by 6.8% of those in the nintedanib arm versus 17.1% with chemotherapy alone.
The ongoing phase III LUME-Meso trial is still actively recruiting patients comparing nintedanib plus chemotherapy to chemotherapy and placebo. The trial now looking exclusively at those with epithelioid MPM. The estimated primary completion date for the study is October 30, 2019 (NCT01907100).
Nowak AK, Grosso F, Steele N, et al. Mature overall survival (OS) results from the LUME-Meso study of nintedanib (N) + pemetrexed/cisplatin (PEM/CIS) vs placebo (P) + PEM/CIS in chemo-naïve patients (pts) with malignant pleural mesothelioma (MPM). J Clin Oncol. 2017;35 (suppl; abstr 8506).
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