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Efficacy and Safety of Nintedanib Plus Docetaxel in Patients with Advanced Lung Adenocarcinoma: Complementary and Exploratory Analyses of the Phase III LUME-Lung 1 Study

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Abstract

Background

Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months.

Objective

This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT.

Patients and Methods

Exploratory analyses were conducted of the overall and European LUME-Lung 1 adenocarcinoma population according to age, prior therapy, and tumor dynamics. Analyses also used TSFLT and time from end of FLT (TEFLT).

Results

Treatment with nintedanib/docetaxel significantly improved OS in European patients independently of age or prior therapy. Analyses of several patient subgroups showed improvements in median OS: TSFLT <6 months, 9.5 versus 7.5 months (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.55–0.98); chemorefractory to FLT, 9.1 versus 6.9 months (HR 0.72, 95% CI 0.52–0.99); progressive disease (PD) as best response to FLT, 9.8 versus 6.3 months (HR 0.62, 95% CI 0.41–0.94); TEFLT ≤6 months, 11.3 versus 8.2 months (HR 0.75, 95% CI 0.61–0.92); and TEFLT <3 months, 11.0 versus 8.0 months (HR 0.74, 95% CI 0.58–0.94).

Conclusions

Nintedanib/docetaxel demonstrated significant OS benefits in adenocarcinoma patients, which were more pronounced in patients with shorter TSFLT or TEFLT, or with PD as best response to FLT.

This study was registered at ClinicalTrials.gov: NCT00805194.

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Acknowledgments

Analyses were conducted by Boehringer Ingelheim. The authors would like to thank the study investigators, study center staff, and all trial participants and their families.

Author information

Authors and Affiliations

  1. Lung Cancer Unit, Meir Medical Center, 4428164, Kfar Saba, Israel

    Maya Gottfried

  2. Département D’Oncologie Médicale, ICO René Gauducheau, 44805, Saint Herblain Cedex, France

    Jaafar Bennouna & Jean-Yves Douillard

  3. Dnepropetovsk Medical Academy, Municipal Clinical Hospital #4, Dnipropetrovsk, 49102, Ukraine

    Igor Bondarenko

  4. Department of Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 22927, Grosshansdorf, Germany

    David F. Heigener & Martin Reck

  5. Oncology Institute, 02-781, Warsaw, Poland

    Maciej Krzakowski

  6. Department of Oncology, Herlev Hospital, 2730, Herlev, Denmark

    Anders Mellemgaard

  7. Thoracic Oncology Unit, AUO San Luigi, Department of Oncology, University of Turin, 10124, Torino, Italy

    Silvia Novello

  8. Department of Thoracic Oncology, GOU VPO St Petersburg State Medical University, St Petersburg, 197022, Russia

    Sergei Orlov

  9. Department of Medical Oncology, Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UK

    Yvonne Summers

  10. Asklepios Fachkliniken München-Gauting, 82131, Gauting, Germany

    Joachim von Pawel

  11. Boehringer Ingelheim Pharma GmbH & Co. KG, 88400, Biberach, Germany

    Julia Stöhr

  12. Boehringer Ingelheim Pharma GmbH & Co. KG, 55216, Ingelheim am Rhein, Germany

    Rolf Kaiser

  13. Johannes Gutenberg University of Mainz, 55122, Mainz, Germany

    Rolf Kaiser

Authors
  1. Maya Gottfried
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  2. Jaafar Bennouna
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  3. Igor Bondarenko
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  4. Jean-Yves Douillard
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  7. Anders Mellemgaard
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  8. Silvia Novello
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  9. Sergei Orlov
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  10. Yvonne Summers
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  11. Joachim von Pawel
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  12. Julia Stöhr
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  13. Rolf Kaiser
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  14. Martin Reck
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Corresponding author

Correspondence to Maya Gottfried.

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Funding

The studies on which this analysis was based, were sponsored by Boehringer Ingelheim. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Aurora O’Brate, PhD, of inVentiv Medical Communications, UK, during the preparation of this manuscript.

Conflicts of Interest

JB has received consulting fees/honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, and Roche. J-YD has received a research grant from Merck Serono for his institution and consulting fees/honorarium and payment for lectures/speakers bureaus from Amgen, AstraZeneca, Bayer, Roche, Sanofi, and Sirtex. AM has received consulting fees/honorarium (advisory board) from Boehringer Ingelheim. DFH has received consulting fees/honoraria from Boehringer Ingelheim, Eli Lilly, Hoffmann-la Roche, and Bristol-Myers Squibb. YS has received consulting fees/honoraria (advisory board), support for travel to a conference, and payment for lectures/speakers bureaus from Boehringer Ingelheim. SN has received payment for lectures/speakers bureaus from Eli Lilly, Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, and AstraZeneca. JS is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG. RK is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG and an applicant on a pending patent for nintedanib. MR has received consulting fees/honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Hoffmann-La Roche, Merck Sharp & Dohme, Novartis, and Pfizer. MG, IB, JvP, MK, and SO have no conflicts of interest to disclose.

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Gottfried, M., Bennouna, J., Bondarenko, I. et al. Efficacy and Safety of Nintedanib Plus Docetaxel in Patients with Advanced Lung Adenocarcinoma: Complementary and Exploratory Analyses of the Phase III LUME-Lung 1 Study. Targ Oncol 12, 475–485 (2017). https://doi.org/10.1007/s11523-017-0517-2

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  • DOI: https://doi.org/10.1007/s11523-017-0517-2

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