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Clinical Trial
. 2017 Dec;80(6):1161-1169.
doi: 10.1007/s00280-017-3438-y. Epub 2017 Oct 17.

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

Heinz-Josef Lenz  1 , 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
Affiliations
Clinical Trial

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

Heinz-Josef Lenz et al. Cancer Chemother Pharmacol. 2017 Dec.

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: Chemotherapy; Etirinotecan pegol; Irinotecan; KRAS mutant; Metastatic colorectal cancer.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
a Progression-free survival by independent review and b Overall survival by treatment group in patients with KRAS-mutant, irinotecan-naive metastatic colorectal cancer
See this image and copyright information in PMC

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