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Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer

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Abstract

Purpose

This study assessed the safety, efficacy, and pharmacokinetics of motesanib, a multitargeted small molecule angiogenesis inhibitor, with and without panitumumab, in combination with FOLFIRI or FOLFOX in patients with metastatic colorectal cancer (mCRC).

Methods

This open-label, phase 1b, two-part, multicenter study in patients with mCRC and ≤1 prior treatment evaluated escalating doses (50, 75, 100, or 125 mg QD, 75 mg BID) of motesanib with panitumumab and chemotherapy (Part 1) and the target dose of motesanib with chemotherapy (Part 2).

Results

At 17 sites in the USA and Australia, 119 patients were enrolled between December 2004 and February 2010. In Part 1 [motesanib plus panitumumab/FOLFIRI (n = 36) or plus panitumumab/FOLFOX (n = 17)], all motesanib doses tested were tolerated and 125 mg QD was deemed the target dose. Following toxicity results for combination therapy in other trials, panitumumab was withdrawn from the study. Part 2 evaluated motesanib 125 mg with chemotherapy [FOLFIRI (n = 37); FOLFOX (n = 29)]. The primary endpoint, objective response rate in patients with measurable disease by RECIST, was 20 % overall and was higher among patients receiving first-line (27 % overall; FOLFOX, 24 %; FOLFIRI, 27 %) compared with second-line therapy (14 % overall; FOLFOX, 0 %; FOLFIRI, 20 %). The most common adverse events were diarrhea, nausea, fatigue, and hypertension. We observed a low rate of cholecystitis [3 of 119 (2.5 %)], a known adverse event of motesanib and other small molecule VEGF inhibitors.

Conclusions

Motesanib 125 mg QD in combination with FOLFIRI or FOLFOX chemotherapy was tolerated and demonstrated modest efficacy in first-/second-line mCRC.

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Acknowledgments

This work was sponsored by Amgen Inc. The authors would like to thank Yining Ye for statistical support; Bethlyn Sloey, Shubhada Kulkarni, and Bernd Bruenner, all of Amgen Inc., for their contribution to PK sample and data analysis; and Wanda Krall, Ph.D., whose work was funded by Amgen Inc., for assistance in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Medical Oncology, Austin Health, Heidelberg, VIC, 3084, Australia

    Niall Tebbutt

  2. Ashford Cancer Centre, Ashford, SA, Australia

    Dusan Kotasek

  3. Sarah Cannon Research Institute, Nashville, TN, USA

    Howard A. Burris

  4. The West Clinic, Memphis, TN, USA

    Lee S. Schwartzberg

  5. Duke University Medical Center, Durham, NC, USA

    Herbert Hurwitz

  6. Cancer Center of the Carolinas, Greenville, SC, USA

    Joe Stephenson

  7. Amgen Inc., Thousand Oaks, CA, USA

    Douglas J. Warner, Lisa Chen & Cheng-Pang Hsu

  8. Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Sydney, NSW, Australia

    David Goldstein

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  1. Niall Tebbutt
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Correspondence to Niall Tebbutt.

Additional information

ClinicalTrials.gov Registration Number: NCT00101894.

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Tebbutt, N., Kotasek, D., Burris, H.A. et al. Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol 75, 993–1004 (2015). https://doi.org/10.1007/s00280-015-2694-y

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