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Phase II study of the combination of S-1 with bevacizumab for patients with previously treated advanced non-squamous non-small-cell lung cancer

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Abstract

Background

We assessed the efficacy and safety of bevacizumab and S-1 chemotherapy for patients with previously treated advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods

This was a prospective single-arm study, including patients with non-squamous NSCLC who had received at least one chemotherapy regimen along with a platinum-based regimen. Bevacizumab 15 mg/kg was intravenously administered every 3 weeks, and S-1 40 mg/m2 was orally administered twice daily from day 1 (evening) through day 15 (morning). The treatment continued for 3 weeks/cycle until disease progression or until unacceptable toxicities occurred. During the lead-in part, six patients were evaluated for dose-limiting toxicity (DLT) rate. In phase II, the primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.

Results

In the lead-in part, we evaluated the safety in the first six patients and observed no DLT. In phase II, a total of 46 patients were enrolled from September 2012 to December 2018. The median follow-up duration was 13.7 months [95% confidence interval (CI) 1.4–72.0]. The ORR was 28.3%. The median PFS and OS were 4.3 (95% CI 2.9–5.9) and 15.0 months (95% CI 9.8–30.3), respectively. The most common adverse events were hypertension (65.2%), diarrhea (47.8%), mucositis oral (45.7%), and proteinuria (43.5%), and the most common grade 3 adverse events were hypertension (23.9%) and proteinuria (6.5%). Grade 4/5 adverse events were not observed.

Conclusion

Bevacizumab and S-1 combination chemotherapy showed high activity and were well tolerated in patients with previously treated advanced non-squamous NSCLC.

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References

  1. Siegel RL, Miller KD, Jemal A (2017) Cancer statistics. CA Cancer J Clin 67(1):7–30. https://doi.org/10.3322/caac.21387

    Article  PubMed  Google Scholar 

  2. Fossella FV, DeVore R, Kerr RN et al (2000) Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 18(12):2354–2362. https://doi.org/10.1200/jco.2000.18.12.2354

    Article  CAS  PubMed  Google Scholar 

  3. Shepherd FA, Dancey J, Ramlau R et al (2000) Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 18(10):2095–2103. https://doi.org/10.1200/jco.2000.18.10.2095

    Article  CAS  PubMed  Google Scholar 

  4. Nokihara H, Lu S, Mok TSK et al (2017) Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer). Ann Oncol 28(11):2698–2706. https://doi.org/10.1093/annonc/mdx419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550. https://doi.org/10.1056/NEJMoa061884

    Article  CAS  PubMed  Google Scholar 

  6. Garon EB, Ciuleanu T-E, Arrieta O et al (2014) Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. The Lancet 384(9944):665–673. https://doi.org/10.1016/s0140-6736(14)60845-x

    Article  CAS  Google Scholar 

  7. Nukatsuka M, Saito H, Nakagawa F et al (2012) Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice. Exp Ther Med 3(5):755–762. https://doi.org/10.3892/etm.2012.484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  9. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10(1):1–10. https://doi.org/10.1016/0197-2456(89)90015-9

    Article  CAS  PubMed  Google Scholar 

  10. Totani Y, Saito Y, Hayashi M et al (2009) A phase II study of S-1 monotherapy as second-line treatment for advanced non-small cell lung cancer. Cancer Chemother Pharmacol 64(6):1181–1185. https://doi.org/10.1007/s00280-009-0981-1

    Article  CAS  PubMed  Google Scholar 

  11. Hanna N, Shepherd FA, Fossella FV et al (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22(9):1589–1597. https://doi.org/10.1200/JCO.2004.08.163

    Article  CAS  PubMed  Google Scholar 

  12. Scagliotti GV, Parikh P, von Pawel J et al (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26(21):3543–3551. https://doi.org/10.1200/JCO.2007.15.0375

    Article  CAS  PubMed  Google Scholar 

  13. Gandhi L, Rodriguez-Abreu D, Gadgeel S et al (2018) Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med 378(22):2078–2092. https://doi.org/10.1056/NEJMoa1801005

    Article  CAS  PubMed  Google Scholar 

  14. Okamoto I, Yoshioka H, Morita S et al (2010) Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer: results of a west Japan oncology group study. J Clin Oncol 28(36):5240–5246. https://doi.org/10.1200/JCO.2010.31.0326

    Article  CAS  PubMed  Google Scholar 

  15. Kubota K, Sakai H, Katakami N et al (2015) A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial. Ann Oncol 26(7):1401–1408. https://doi.org/10.1093/annonc/mdv190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu W, Zhang J, Yao X et al (2018) Bevacizumab-enhanced antitumor effect of 5-fluorouracil via upregulation of thymidine phosphorylase through vascular endothelial growth factor A/vascular endothelial growth factor receptor 2-specificity protein 1 pathway. Cancer Sci 109(10):3294–3304. https://doi.org/10.1111/cas.13779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nishino K, Imamura F, Kumagai T et al (2015) A randomized phase II study of bevacizumab in combination with docetaxel or S-1 in patients with non-squamous non-small-cell lung cancer previously treated with platinum based chemotherapy (HANSHIN Oncology Group 0110). Lung Cancer 89(2):146–153. https://doi.org/10.1016/j.lungcan.2015.05.022

    Article  PubMed  Google Scholar 

  18. Yamada K, Ichiki M, Takahashi K et al (2016) A multicenter phase II trial of S-1 combined with bevacizumab after platinum-based chemotherapy in patients with advanced non-squamous non-small cell lung cancer. Cancer Chemother Pharmacol 78(3):501–507. https://doi.org/10.1007/s00280-016-3101-z

    Article  CAS  PubMed  Google Scholar 

  19. Nishijima-Futami Y, Minami S, Futami S et al (2017) Phase II study of S-1 plus bevacizumab combination therapy for patients previously treated for non-squamous non-small cell lung cancer. Cancer Chemother Pharmacol 79(6):1215–1220. https://doi.org/10.1007/s00280-017-3321-x

    Article  CAS  PubMed  Google Scholar 

  20. Ohyanagi F, Yanagitani N, Kudo K et al (2014) Phase II study of docetaxel-plus-bevacizumab combination therapy in patients previously treated for advanced non-squamous non-small cell lung cancer. Anticancer Res 34(9):5153–5158

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all the study participants who provided clinical data for the analysis.

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Authors and Affiliations

  1. Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Tsukasa Hasegawa, Noriko Yanagitani, Fumiyoshi Ohyanagi, Keita Kudo, Atsushi Horiike, Yuichi Tambo, Shingo Nishikawa, Ryo Ariyasu, Ken Uchibori, Satoru Kitazono & Makoto Nishio

  2. Division of Pulmonary Medicine, Clinical Department of Internal Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Fumiyoshi Ohyanagi

  3. Department of Medical Oncology and Respiratory Medicine, National Hospital Organization Osaka Minami Medical Center, Osaka, Japan

    Keita Kudo

  4. Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan

    Atsushi Horiike

  5. Department of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan

    Yuichi Tambo & Shingo Nishikawa

Authors
  1. Tsukasa Hasegawa
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  2. Noriko Yanagitani
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  3. Fumiyoshi Ohyanagi
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  4. Keita Kudo
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  5. Atsushi Horiike
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  7. Shingo Nishikawa
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  10. Satoru Kitazono
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  11. Makoto Nishio
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Contributions

KK, FO and MN contributed to the study concept and design and all authors approved it. TH, NY, and MN were involved in statistical analysis of the patient data and writing of the article. TH, NY, FO, KK, AH, YT, SN, RA, KU, SK, and MN were involved in patient clinical data collection. TH wrote the first draft of the manuscript, and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Makoto Nishio.

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Conflict of interest

Makoto Nishio reports honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Boehringer-ingelheim, MSD, and Novartis, research funding from Novartis, Daiichi Sankyo, Taiho Pharmaceutical, Bristol-Myers Squibb, Boehringer-ingelheim, Ono Pharmaceutical, Eli Lilly, Chugai Pharmaceutical, AstraZeneca, Merck Sernon, MSD and Pfizer. Atsushi Horiike reports honoraria from Chugai Pharmaceutical and Taiho Pharmaceutical, research funding from Chugai Pharmaceutical. Noriko Yanagitani reports employment/leadership position/ advisory role of Chugai Pharmaceutical. Yuichi Tambo reports honoraria from AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical and MSD. Ken Uchibori reports employment/leadership position/ advisory role of Daiichi Sankyo. All the other authors have stated that they have no conflicts of interest.

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Hasegawa, T., Yanagitani, N., Ohyanagi, F. et al. Phase II study of the combination of S-1 with bevacizumab for patients with previously treated advanced non-squamous non-small-cell lung cancer. Int J Clin Oncol 26, 507–514 (2021). https://doi.org/10.1007/s10147-020-01822-7

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  • DOI: https://doi.org/10.1007/s10147-020-01822-7

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