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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2017

01-12-2017 | Original Article

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

Authors: Heinz-Josef Lenz, Philip Philip, Mark Saunders, Tatjana Kolevska, Kalyan Mukherjee, Leslie Samuel, Shailesh Bondarde, Tracy Dobbs, Mary Tagliaferri, Ute Hoch, Alison L. Hannah, Maurice Berkowitz

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2017

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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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Metadata
Title
Randomized study of etirinotecan pegol versus irinotecan as second-line treatment for metastatic colorectal cancer
Authors
Heinz-Josef Lenz
Philip Philip
Mark Saunders
Tatjana Kolevska
Kalyan Mukherjee
Leslie Samuel
Shailesh Bondarde
Tracy Dobbs
Mary Tagliaferri
Ute Hoch
Alison L. Hannah
Maurice Berkowitz
Publication date
01-12-2017
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-017-3438-y

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