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A phase 1b, multicenter, open-label, dose-finding study of eribulin in combination with carboplatin in advanced solid tumors and non-small cell lung cancer

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Abstract

Purpose

This phase 1b study investigated the maximum tolerated dose (MTD; primary objective), safety, pharmacokinetics, and antitumor activity (secondary objectives) of eribulin combined with carboplatin in patients with solid tumors and, in particular, non-small cell lung cancer (NSCLC).

Methods

Two dose-escalation schemes were evaluated with carboplatin, at an area under the curve (AUC) of either 5 or 6 mg/mL·min. Eribulin, dose-escalated from 0.7 to 1.4 mg/m2 was administered 1 h before (Schedule A) or after (Schedule B) carboplatin as a 2–5-min bolus infusion on days 1 and 8 of a 21-day cycle. Following tolerability assessment, patients with NSCLC were recruited in an expansion cohort.

Results

The MTDs were eribulin 1.4 and 1.1 mg/m2 with carboplatin AUC 5 and AUC 6, respectively. The latter combination was used to treat NSCLC patients in the expansion cohort. Pharmacokinetics of eribulin and carboplatin were generally unaffected by administration sequence (i.e., administration of carboplatin did not significantly affect eribulin Cmax and AUC0–t and the converse was also observed). In the NSCLC cohort, the objective response rate was 27%. Median overall and progression-free survival durations were 12.1 and 4.2 months, respectively. No unexpected safety findings were observed.

Conclusions

The combination of eribulin and carboplatin demonstrated antitumor activity; however, recent therapeutic advances may be more promising approaches for first-line treatment of NSCLC.

Clinical trial registration NCT00268905.

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Acknowledgements

We thank all the patients and investigators who participated in this study. We would also like to thank Gresel Martinez of Eisai Inc., USA, Paloma Salazar of Eisai Ltd., UK. Editorial support, funded by Eisai Inc., was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA. This study was funded by Eisai Inc.

Funding

Editorial support for this manuscript and styling for submission were provided by Oxford PharmaGenesis Inc, Newtown, PA, USA, and this support was funded by Eisai Inc., Woodcliff Lake, NJ, USA.

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Authors and Affiliations

  1. Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Road, Bronx, NY, 10461, USA

    Sanjay Goel

  2. University of Iowa Hospitals and Clinics, Iowa City, IA, USA

    Umang Swami

  3. Meenakshi Mission Hospital and Research Center, Madurai, Tamil Nadu, India

    Kirushna Kumar

  4. Ludwig Boltzmann Institute for Applied Cancer Research and Applied Cancer Research–Institution for Translational Research Vienna, Center for Oncology and Hematology, Kaiser Franz Josef-Spital, Vienna, Austria

    Christian Dittrich

  5. Eisai Inc., Woodcliff Lake, NJ, USA

    Larisa Reyderman & James Song

  6. Ruby Hall Clinic, Pune, Maharashtra, India

    Minish Jain

  7. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Joseph Aisner

  8. Yale University Cancer Center, New Haven, CT, USA

    Daniel P. Petrylak

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  1. Sanjay Goel
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Corresponding author

Correspondence to Sanjay Goel.

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Conflict of interest

Sanjay Goel: received funding for the study from Eisai Inc. Kirushna Kumar: received grant for conducting the study from Eisai. Christian Dittrich: received an unrestricted research grant from Eisai. Larisa Reyderman: employee of Eisai Inc. Joseph Aisner: received remuneration for DMC panels from Bristol-Myers Squibb and Merck-Serono. James Song: former employee of Eisai Inc. Daniel P. Petrylak: received consultant fees from AstraZeneca, Bayer, Bellicum, Dendreon, Exelixis, Ferring, Johnson and Johnson, Lilly, Medivation, Millennium, Pfizer, Roche Laboratories, and Sanofi Aventis (Tyme pharmaceuticals discontinued 1/31/17). Received grant support from Agensys, AstraZeneca, Bayer, Clovis, Dendreon, Eli Lilly, Endocyte, Genentech, Innocrin, Johnson and Johnson, Lilly, MedImmune, Medivation, Merck, Millennium, Novartis, Pfizer, Progenics, Roche Laboratories, Sanofi Aventis, and Sotio. Has ownership interest/investment in Bellicum, Tyme. Umang Swami and Minish Jain: no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Goel, S., Swami, U., Kumar, K. et al. A phase 1b, multicenter, open-label, dose-finding study of eribulin in combination with carboplatin in advanced solid tumors and non-small cell lung cancer. Cancer Chemother Pharmacol 84, 567–578 (2019). https://doi.org/10.1007/s00280-019-03877-4

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