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Nab-paclitaxel maintenance therapy following carboplatin + nab-paclitaxel combination therapy in chemotherapy naïve patients with advanced non-small cell lung cancer: multicenter, open-label, single-arm phase II trial

  • PHASE II STUDIES
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Summary

Background A global multicenter study demonstrated superiority of carboplatin + nab-paclitaxel (PTX) therapy compared to carboplatin + PTX in terms of response rate (RR) and non-inferiority in terms of progression free survival (PFS) and overall survival (OS) in untreated patients with stage IIIB/IV non-small cell lung cancer; no clinical findings have so far been reported on maintenance therapies with nab-PTX. The aim of this study was to determine the efficacy and safety of maintenance therapy with nab-PTX following carboplatin + nab-PTX combination therapy. Methods Carboplatin (AUC 6) was administered on Day 1; and nab-PTX 100 mg/m2 on Days 1, 8, and 15, and dosing was repeated in 4 courses of 4 weeks each. In patients with clinical response was observed at the end of the 4th course, nab-PTX maintenance therapy was repeated. Results Out of 39 patients included in the efficacy analysis, 19 (48.7%) patients completed the induction therapy and 15 (38.5%) were transitioned to maintenance therapy. The median PFS in the maintenance phase was 6.5 (90%CI 1.4–11.4) months. The median OS in 15 patients was 12.6 (95%CI: 7.4-not reached). Grade ≥ 3 toxicities observed in more than 5% of patients were neutropenia (55.0%), anemia (15.0%), and febrile neutropenia (5.0%), with no increase during the maintenance phase. Conclusions Although statistically significance was not demonstrated presumably due to a limited transition rate from induction to maintenance phase, nab-PTX was suggested to be a useful treatment option following the induction therapy with nab-PTX in patients with advanced NSCLC.

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Acknowledgements

Clinical Research Support Center Kyushu, incorporated non-profit organization, supported research at individual study centers, and conducted data collection and data management. We appreciate the assistance by Ms. Ritsuko Kondo for editing the manuscript. The authors thank all the investigators and the patients who participated in the study.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Akira Nakao and Junji Uchino contributed equally to this work

Authors and Affiliations

  1. Department of Respiratory Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, Fukuoka, 814-0180, Japan

    Akira Nakao, Fumiyasu Igata, Rintaro On, Takato Ikeda, Hiroshi Yatsugi, Ryosuke Hirano, Tomoya Sasaki, Kentaro Watanabe & Masaki Fujita

  2. Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, 410 Kajii-cho, Hirokoji-agaru, kawaramachi-dori, Kamigyo-ku, Kyoto, Kyoto, 602-0857, Japan

    Junji Uchino, Keiko Tanimura, Tatsuya Imabayashi, Nobuyo Tamiya, Yoshiko Kaneko, Tadaaki Yamada & Koichi Takayama

  3. Department of Respiratory Medicine, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyoin, Chikushino, Fukuoka, 818-0067, Japan

    Nobuhiko Nagata

  4. Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan

    Junji Kishimoto

Authors
  1. Akira Nakao
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  2. Junji Uchino
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  4. Rintaro On
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  12. Yoshiko Kaneko
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  16. Junji Kishimoto
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  18. Masaki Fujita
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Contributions

Junji Uchino and Masaki Fujita contributed to the study concept and design, and supervised the study. All authors contributed to acquisition of data. Junji Uchino drafted the report, and all other authors critically reviewed and revised the report for important intellectual content. Junji Kishimoto did the statistical analysis, and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Junji Uchino.

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Conflicts of interests

J Uchino reports grants from Eli Lilly Japan K.K., outside the submitted work. T Yamada reports grants from Nippon Boehringer Ingelheim Co., Ltd., and Ono Pharmaceutical Co., Ltd., outside the submitted work. K Takayama reports grants from Chugai-Roche Co., grants from Ono Pharmaceutical Co., personal fees from Astrazeneca Co., personal fees from Chugai-Roche Co., personal fees from MSD-Merck Co., personal fees from Eli Lilly Co., personal fees from Boehringer-Ingelheim Co., personal fees from Daiichi-Sankyo Co., outside the submitted work. A Nakao, F Igata, R On, T Ikeda, H Yatsugi, R Hirano, T Sasaki, K Tanimura, T Imabayashi, N Tamiya, Y Kaneko, N Nagata, K Watanabe, J Kishimoto, and M Fujita have no conflict of interest to declare.

Ethical approval

The present study was conducted in accordance with the Declaration of Helsinki and “Ethical Guidelines for Medical and Health Research Involving Human Subjects”. The study protocol was approved by the ethics committee of each institution participating in this study. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Patients were given written informed consent forms approved by the Ethics Committees, were fully informed about the study in writing, and then freely signed their consent forms.

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Nakao, A., Uchino, J., Igata, F. et al. Nab-paclitaxel maintenance therapy following carboplatin + nab-paclitaxel combination therapy in chemotherapy naïve patients with advanced non-small cell lung cancer: multicenter, open-label, single-arm phase II trial. Invest New Drugs 36, 903–910 (2018). https://doi.org/10.1007/s10637-018-0617-6

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  • DOI: https://doi.org/10.1007/s10637-018-0617-6

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