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Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 6, pp 1161–1169 | Cite as

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

  • Heinz-Josef LenzEmail author
  • Philip Philip
  • Mark Saunders
  • Tatjana Kolevska
  • Kalyan Mukherjee
  • Leslie Samuel
  • Shailesh Bondarde
  • Tracy Dobbs
  • Mary Tagliaferri
  • Ute Hoch
  • Alison L. Hannah
  • Maurice Berkowitz
Original Article

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.

Keywords

Etirinotecan pegol Metastatic colorectal cancer Irinotecan KRAS mutant Chemotherapy 

Notes

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.

Compliance with ethical standards

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.

Supplementary material

280_2017_3438_MOESM1_ESM.pdf (93 kb)
Supplementary material 1 (PDF 92 KB)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Heinz-Josef Lenz
    • 1
    Email author
  • Philip Philip
    • 2
    • 3
  • Mark Saunders
    • 4
  • Tatjana Kolevska
    • 5
  • Kalyan Mukherjee
    • 6
  • Leslie Samuel
    • 7
  • Shailesh Bondarde
    • 8
  • Tracy Dobbs
    • 9
  • Mary Tagliaferri
    • 10
  • Ute Hoch
    • 10
  • Alison L. Hannah
    • 10
  • Maurice Berkowitz
    • 11
  1. 1.USC Norris Comprehensive Cancer CenterLos AngelesUSA
  2. 2.Barbara Ann Karmanos Cancer InstituteDetroitUSA
  3. 3.Wayne State UniversityDetroitUSA
  4. 4.Christie Hospital NHS Foundation TrustManchesterUK
  5. 5.Kaiser Permanente Medical CenterVallejoUSA
  6. 6.Chittaranjan National Cancer InstituteKolkataIndia
  7. 7.ANCHOR Unit Clinic D, Aberdeen Royal InfirmaryAberdeenUK
  8. 8.Shatabdi Super Specialty Hospital, Suyojit City CenterNashikIndia
  9. 9.Tennessee Cancer SpecialistsKnoxvilleUSA
  10. 10.Nektar TherapeuticsSan FranciscoUSA
  11. 11.UCLA Geffen School of MedicineBurbankUSA

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