Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial
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Published version
Author(s)
Type
Journal Article
Abstract
Purpose
LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of
nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM).
Phase II results are reported here.
Patients and Methods
Chemotherapy-na¨ıve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative
Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were
randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib
(200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression.
The primary end point was progression-free survival (PFS).
Results
Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin
cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for
placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017),
which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend
toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319).
Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR,
0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and
median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v
placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade $ 3 adverse event (AE;
nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib
group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those
receiving nintedanib versus 17.1% of those in the placebo group.
Conclusion
Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were
manageable. The clinical benefit was evident in patients with epithelioid histology. The confirmatory
phase III part of the study is ongoing.
LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of
nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM).
Phase II results are reported here.
Patients and Methods
Chemotherapy-na¨ıve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative
Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were
randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib
(200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression.
The primary end point was progression-free survival (PFS).
Results
Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin
cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for
placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017),
which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend
toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319).
Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR,
0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and
median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v
placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade $ 3 adverse event (AE;
nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib
group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those
receiving nintedanib versus 17.1% of those in the placebo group.
Conclusion
Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were
manageable. The clinical benefit was evident in patients with epithelioid histology. The confirmatory
phase III part of the study is ongoing.
Date Issued
2017-11-01
Date Acceptance
2017-09-01
Citation
Journal of Clinical Oncology, 2017, 35 (31), pp.3591-3600
ISSN
0732-183X
Publisher
American Society of Clinical Oncology
Start Page
3591
End Page
3600
Journal / Book Title
Journal of Clinical Oncology
Volume
35
Issue
31
Copyright Statement
© 2017 by American Society of Clinical
Oncology
Oncology
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
CELL LUNG-CANCER
TRIPLE ANGIOKINASE INHIBITOR
LEUKEMIA GROUP-B
OPEN-LABEL
BIBF 1120
GROWTH-FACTOR
DOUBLE-BLIND
EXPRESSION
BEVACIZUMAB
COMBINATION
Publication Status
Published