Nasser H Hanna1, Rolf Kaiser2, Richard N Sullivan3, Osvaldo Rudy Aren4, Myung-Ju Ahn5, Beatrice Tiangco6, Isabelle Voccia7, Joachim von Pawel8, Vladimir Kovcin9, Jason Agulnik10, Birgit Gaschler-Markefski11, José Barrueco12, Patricia Sikken11, Charles Schloss12, Joo-Hang Kim13. 1. Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indiana University, Indianapolis, IN, USA. Electronic address: nhanna@iupui.edu. 2. Boehringer Ingelheim Pharmaceuticals GmbH & Co. KG, Biberach, Germany; Institute of Clinical Pharmacology, Georg-August-University Göttingen, Germany. 3. Department of Oncology, Auckland City Hospital, Auckland, New Zealand. 4. Instituto Nacional del Cáncer, Santiago, Chile. 5. Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 6. Internal Medicine, National Kidney and Transplant Institute, Quezon City, Philippines. 7. Boehringer Ingelheim (Canada) Ltd, Burlington, ON, Canada. 8. Pneumology Clinic, Asklepios Fachkliniken, Gauting, Germany. 9. Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia. 10. Jewish General Hospital, Montréal, Québec, Canada. 11. Boehringer Ingelheim Pharmaceuticals GmbH & Co. KG, Biberach, Germany. 12. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. 13. Yonsei Cancer Center, Yonsei University Health System, Seoul, South Korea.
Abstract
OBJECTIVES: LUME-Lung 2 investigated the efficacy/safety of nintedanib plus pemetrexed in patients with pretreated non-squamous non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with stage IIIB/IV or recurrent non-squamous NSCLC who had received one prior chemotherapy regimen were randomized (1:1 stratified by histology [adenocarcinoma/non-adenocarcinoma], prior bevacizumab, Eastern Cooperative Oncology Group performance status and presence of brain metastases) to receive intravenous pemetrexed 500mg/m2 on Day 1 plus nintedanib 200mg orally twice daily or matching placebo on Days 2-21, every 3 weeks until progression/unacceptable toxicity. Progression-free survival (PFS) by independent central review was the primary endpoint. Overall survival (OS) was the key secondary endpoint. RESULTS: Based on the pre-planned futility analysis of investigator-assessed PFS, conducted by an independent data monitoring committee, recruitment was halted on 18 June 2011 after 713 (n=353 nintedanib/pemetrexed; n=360 placebo/pemetrexed)/1300 planned patients had enrolled. There were no safety concerns. Subsequent analysis demonstrated a significant improvement in PFS favoring nintedanib/pemetrexed over placebo/pemetrexed (median 4.4 months vs 3.6 months; hazard ratio [HR]=0.83, 95% confidence interval [CI] 0.70-0.99, p=0.0435). There was no significant difference in OS (median 12.0 months vs 12.7 months; HR=1.01, 95% CI 0.85-1.21, p=0.8940) after 514 deaths. Nintedanib/pemetrexed resulted in a higher incidence of grade ≥3 elevated alanine aminotransferase (23.3% vs 7.3%), elevated aspartate aminotransferase (12.1% vs 1.7%) and diarrhea (3.5% vs 1.1%) compared with placebo/pemetrexed, but no difference in hypertension, bleeding or thrombosis. CONCLUSION: Although recruitment stopped prematurely, combining nintedanib with pemetrexed significantly prolonged PFS in patients with advanced non-squamous NSCLC after first-line chemotherapy, with a manageable safety profile.
RCT Entities:
OBJECTIVES: LUME-Lung 2 investigated the efficacy/safety of nintedanib plus pemetrexed in patients with pretreated non-squamous non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:Patients with stage IIIB/IV or recurrent non-squamous NSCLC who had received one prior chemotherapy regimen were randomized (1:1 stratified by histology [adenocarcinoma/non-adenocarcinoma], prior bevacizumab, Eastern Cooperative Oncology Group performance status and presence of brain metastases) to receive intravenous pemetrexed 500mg/m2 on Day 1 plus nintedanib 200mg orally twice daily or matching placebo on Days 2-21, every 3 weeks until progression/unacceptable toxicity. Progression-free survival (PFS) by independent central review was the primary endpoint. Overall survival (OS) was the key secondary endpoint. RESULTS: Based on the pre-planned futility analysis of investigator-assessed PFS, conducted by an independent data monitoring committee, recruitment was halted on 18 June 2011 after 713 (n=353 nintedanib/pemetrexed; n=360 placebo/pemetrexed)/1300 planned patients had enrolled. There were no safety concerns. Subsequent analysis demonstrated a significant improvement in PFS favoring nintedanib/pemetrexed over placebo/pemetrexed (median 4.4 months vs 3.6 months; hazard ratio [HR]=0.83, 95% confidence interval [CI] 0.70-0.99, p=0.0435). There was no significant difference in OS (median 12.0 months vs 12.7 months; HR=1.01, 95% CI 0.85-1.21, p=0.8940) after 514 deaths. Nintedanib/pemetrexed resulted in a higher incidence of grade ≥3 elevated alanine aminotransferase (23.3% vs 7.3%), elevated aspartate aminotransferase (12.1% vs 1.7%) and diarrhea (3.5% vs 1.1%) compared with placebo/pemetrexed, but no difference in hypertension, bleeding or thrombosis. CONCLUSION: Although recruitment stopped prematurely, combining nintedanib with pemetrexed significantly prolonged PFS in patients with advanced non-squamous NSCLC after first-line chemotherapy, with a manageable safety profile.
Authors: Ravi Paluri; Ankit Madan; Peng Li; Benjamin Jones; Mansoor Saleh; Mary Jerome; Deborah Miley; Jennifer Keef; Francisco Robert Journal: Cancer Chemother Pharmacol Date: 2019-01-02 Impact factor: 3.333
Authors: Birgit Gaschler-Markefski; Patricia Sikken; John V Heymach; Maya Gottfried; Anders Mellemgaard; Silvia Novello; Claudia-Nanette Gann; José Barrueco; Martin Reck; Nasser H Hanna; Rolf Kaiser Journal: ESMO Open Date: 2017-04-11