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Randomized study of etirinotecan pegol versus irinotecan as second-line treatment for metastatic colorectal cancer

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Abstract

Purpose

Etirinotecan pegol (EP) is a long-acting topoisomerase-I inhibitor designed to provide sustained exposure to SN-38 (active metabolite of irinotecan). This phase II study compared EP versus irinotecan as second-line treatment for KRAS-mutant, irinotecan-naïve, metastatic colorectal cancer (mCRC).

Methods

Patients were randomized to EP 145 mg/m2 or irinotecan 350 mg/m2 Q21d until disease progression/unacceptable toxicity. The primary endpoint was progression-free survival (PFS) with response determined by central radiologic review (RECIST version 1.1).

Results

The study was terminated before completing accrual due to evolving standards of care. Eighty-three patients were randomized. Median PFS was longer with EP versus irinotecan (4.0 versus 2.8 months, respectively; HR 0.65; 95% CI 0.40–1.04; P = 0.07). Six-month PFS rates were 32.8 and 15.4%, respectively. Median OS was 9.6 and 8.4 months in EP and irinotecan arms, respectively (HR 0.91; 95% CI 0.56–1.49). ORRs were 10 and 5%, respectively (P = 0.676); median DOR was significantly longer in EP arm (7.9 versus 1.4 months; P = 0.018). The most common grade-3/4 adverse events for EP and irinotecan were diarrhea (21 vs 20%), neutropenia (10 vs 22%), abdominal pain (14 vs 5%), nausea (14 vs 2%), and vomiting (12 vs 7%), respectively.

Conclusion

EP is active and safe for second-line treatment of KRAS-mutant, irinotecan-naïve mCRC.

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Acknowledgements

Gregg Olsen, MD, East Valley Hematology and Oncology Medical Center, Sherman Oaks, CA, USA for enrolling patients; Phillips Gilmore Oncology Communications, Inc. for medical writing assistance, funded by Nektar Therapeutics.

Author information

Authors and Affiliations

  1. USC Norris Comprehensive Cancer Center, 1441 Eastlake Ave Rm 3456, Los Angeles, CA, 90089-9173, USA

    Heinz-Josef Lenz

  2. Barbara Ann Karmanos Cancer Institute, 4th Fl, HWCRC 4100 John R Detroit, Detroit, MI, 48201, USA

    Philip Philip

  3. Wayne State University, Detroit, MI, USA

    Philip Philip

  4. Christie Hospital NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK

    Mark Saunders

  5. Kaiser Permanente Medical Center, 2nd Floor, Hallway C, 975 Sereno Drive, Vallejo, CA, 94589, USA

    Tatjana Kolevska

  6. Chittaranjan National Cancer Institute, 37 Shyama Prasad Mukherjee Road, Bhawanipur, Kolkata, West Bengal, 700026, India

    Kalyan Mukherjee

  7. ANCHOR Unit Clinic D, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZN, UK

    Leslie Samuel

  8. Shatabdi Super Specialty Hospital, Suyojit City Center, Mumbai Naka, Nashik, 422 005, India

    Shailesh Bondarde

  9. Tennessee Cancer Specialists, 1415 Old Weisgarser Road, Knoxville, TN, 37909-1292, USA

    Tracy Dobbs

  10. Nektar Therapeutics, 455 Mission Bay Boulevard South, San Francisco, CA, 94158, USA

    Mary Tagliaferri, Ute Hoch & Alison L. Hannah

  11. UCLA Geffen School of Medicine, 201 S. Buena Vista Street, Suite 200, Burbank, CA, 91505, USA

    Maurice Berkowitz

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Corresponding author

Correspondence to Heinz-Josef Lenz.

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Conflict of interest

Research support provided by Nektar Therapeutics. Philip Philip reports grant support from Bayer, Merck, Novartis, Celgene, Incyte, Lilly. Mary Tagliaferri and Ute Hoch report employment with Nektar Therapeutics. Alison Hannah reports consultancy fees from Nektar Therapeutics. The remaining authors have nothing to report.

Ethical approval

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.

Informed consent

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

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Lenz, HJ., Philip, P., Saunders, M. et al. Randomized study of etirinotecan pegol versus irinotecan as second-line treatment for metastatic colorectal cancer. Cancer Chemother Pharmacol 80, 1161–1169 (2017). https://doi.org/10.1007/s00280-017-3438-y

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  • DOI: https://doi.org/10.1007/s00280-017-3438-y

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