Randomized study of etirinotecan pegol versus irinotecan as second-line treatment for metastatic colorectal cancer
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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).
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).
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.
EP is active and safe for second-line treatment of KRAS-mutant, irinotecan-naïve mCRC.
KeywordsEtirinotecan pegol Metastatic colorectal cancer Irinotecan KRAS mutant Chemotherapy
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.
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 was obtained from all individual participants included in the study.
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