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Phase 2 study of bevacizumab plus carboplatin/nab-paclitaxel followed by bevacizumab plus nab‐paclitaxel for non‐squamous non‐small cell lung cancer with malignant pleural effusion

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Summary

Objectives Vascular endothelial growth factor plays an important role in the pathogenesis of malignant pleural effusion (MPE). We previously showed the efficacy of bevacizumab (Bev) plus carboplatin (CBDCA)/paclitaxel (PTX) in the treatment of non-small lung cell cancer (NSCLC) with MPE. However, the toxicities were a little severe, and the efficacy was not satisfied sufficiently. Therefore, we conducted a phase II study for NSCLC with MPE to evaluate the efficacy and safety of Bev plus CBDCA/nab-PTX, which is a new combination therapy. Methods Chemotherapy-naive non-squamous (SQ) NSCLC patients with MPE participated in the study. A single aspiration (not allowing chest tube drainage) was allowed before chemotherapy. Patients received a maximum of six cycles of Bev (15 mg/kg, day1) plus CBDCA (AUC 6, day1)/nab-PTX (100 mg/m2, day1, 8) every 3 weeks followed by Bev (15 mg/kg, day1) plus nab-PTX (100 mg/m2, day1, 8) every 3 weeks without disease progression or unacceptable severe toxicities. The primary endpoint was objective response rate (ORR). Results The study enrollment was ceased because of suspension of the registration period (as scheduled) after 12 of 20 planned patients were treated successfully between March 2014 and February 2018. The ORR was 58.3 % (95 % CI, 27.7–84.8 %), and the disease control rate was 100 % (95 % CI, 73.5–100 %). Eight patients received maintenance therapy. Median progression-free and overall survival times were 14.4 and 26.9 months, respectively. Most patients experienced hematological toxicities, including ≥ grade 3 neutropenia and anemia; none experienced severe bleeding events and grade 5 toxicities. Conclusion The combination of Bev plus CBDCA/nab-PTX, a novel combination, might have efficacy with acceptable toxicities in chemotherapy-naïve non-SQ NSCLC patients with MPE.

Trial Registration University Hospital Medical Information Network in Japan (UMIN) Clinical Trials Registry (No. UMIN000013329) registered on 4th March 2014.

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Data availability

The datasets are available from the corresponding author on reasonable request.

Abbreviations

NSCLC:

non-small lung cell cancer

MPE:

malignant pleural effusion

PFS:

progression-free survival

OS:

overall survival

DCR:

disease control rate

AEs:

adverse events

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Acknowledgements

The authors thank all the participants and their families, and all caregivers involved in the present study. We would like to thank Editage (www.editage.com) for English language editing.

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Authors and Affiliations

  1. Department of Thoracic Oncology, Osaka International Cancer Institute, Chuo-ku Otemae 3-1- 69, Osaka City, Osaka, 541-8567, Japan

    Motohiro Tamiya, Toru Kumagai & Fumio Imamura

  2. Department of Thoracic Oncology, Kinki-Chuo Chest Medical Center, Kitaku Nagasone-cho 1180, Sakai City, Osaka, 591-8555, Japan

    Akihiro Tamiya, Yoshihiko Taniguchi, Kanako Katayama, Shojiro Minomo, Keiko Nakao, Naoko Takeuchi & Yoshinobu Matsuda

  3. Department of Thoracic Malignancy, Osaka Habikino Medical Center, Habikino 3-7-1, 583-8588, Habikino City, Osaka, Japan

    Hidekazu Suzuki, Norio Okamoto & Tomonori Hirashima

  4. Department of Respiratory Medicine and Clinical Immunology, Osaka University, Yamadaoka 2-15, 565-0871, Suita City, Osaka, Japan

    Yujiro Naito & Takayuki Shiroyama

  5. Department of Clinical Research Center, Kinki-Chuo Chest Medical Center, Kitaku Nagasone- cho 1180, Sakai City, Osaka, 591-8555, Japan

    Kyoichi Okishio & Shinji Atagi

Authors
  1. Motohiro Tamiya
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  2. Akihiro Tamiya
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  3. Hidekazu Suzuki
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  11. Takayuki Shiroyama
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Contributions

Motohiro Tamiya amd Akihiro Tamiya designed the study and wrote the initial draft of the manuscript. Motohiro Tamiya, Akihiro Tamiya, and Hidekazu Suzuki assisted in the preparation of the manuscript. All other authors have contributed to collect data and review the manuscript. All authors approved the version of the manuscript finally and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Motohiro Tamiya.

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Conflict of interest

Tamiya M. reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Ono Pharmaceutical, personal fees from MSD, personal fees from AstraZeneca, personal fees from Taiho Pharmaceutical, personal fees from Eli Lilly, personal fees from Asahi Kasei Pharmaceutical, personal fees from Chugai Pharmaceutical, outside the submitted work. Tamiya A. reports personal fees from Chugai Pharmaceutical, grants and personal fees from AstraZeneka, personal fees from Eli Lilly, personal fees from Boehringer Ingelheim, grants and personal fees from Ono Pharmaceutical, grants and personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Taiho, personal fees from Pfizer, personal fees from Kissei, outside the submitted work. Taniguchi Y. reports personal fees from Chugai Pharmaceutical, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Ono Pharmaceutical, personal fees from Boehringer Ingelheim, personal fees from MSD, personal fees from AstraZeneca, personal fees from Mundipharma, personal fees from Taiho Pharmaceutical, outside the submitted work. Kumagai T. reports grants and personal fees from Ono Pharmaceutical, grants and personal fees from MSD, grants and personal fees from AstraZeneca, grants and personal fees from Takeda Pharmaceutical, grants and personal fees from Taiho Pharmaceutical, grants and personal fees from Eli Lilly, grants and personal fees from Novartis Pharmaceutical, grants from Merck Serono, grants from Pfizer, grants from Boehringer lngelheim, personal fees from Teijin Pharmaceutical, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Chugai Pharmaceutical, outside the submitted work. Atagi A. reports grants and personal fees from AstraZeneca, grants and non-financial support from F. Hoffmann-La Roche, grants and personal fees from Ono Phermaceutical, grants and personal fees from Taiho Phermaceutical, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Pfizer, grants and personal fees from Bristol-Myers Squibb, personal fees from Hisamitsu, grants and personal fees from MSD, grants and personal fees from Eli Lilly, personal fees from Kyowa Hakko Kirin, grants and personal fees from Merck Serono, grants and personal fees from Chugai Phermaceutical, outside the submitted work. Suzuki H, Katayama K, Minomo S, Nakao K, Takeuchi N, Matsuda Y, Naito Y, Shiroyama T, Okamoto N, Okishio K, Imamura F, Hirashima T has nothing to disclose. 

Ethical approval and consent to participate

Institutional review board (IRB) approval for this study was obtained from the Medical Research Ethics Committee of Osaka International Cancer Institute, Osaka Habikino Medical Center, and Kinki-Chuo Chest Medical Center (Osaka International Cancer Institute: No.1,609,019,097, Osaka Habikino Medical Center: No.662, Kinki-Chuo Chest Medical Center: No.460). We got written informed consent before study-specific procedures from all patients.

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All patients provided written informed consent for publication before enrollment.

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Tamiya, M., Tamiya, A., Suzuki, H. et al. Phase 2 study of bevacizumab plus carboplatin/nab-paclitaxel followed by bevacizumab plus nab‐paclitaxel for non‐squamous non‐small cell lung cancer with malignant pleural effusion. Invest New Drugs 39, 1106–1112 (2021). https://doi.org/10.1007/s10637-021-01076-8

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