Heinz-Josef Lenz1, Philip Philip2,3, Mark Saunders4, Tatjana Kolevska5, Kalyan Mukherjee6, Leslie Samuel7, Shailesh Bondarde8, Tracy Dobbs9, Mary Tagliaferri10, Ute Hoch10, Alison L Hannah10, Maurice Berkowitz11. 1. USC Norris Comprehensive Cancer Center, 1441 Eastlake Ave Rm 3456, Los Angeles, CA, 90089-9173, USA. lenz@med.usc.edu. 2. Barbara Ann Karmanos Cancer Institute, 4th Fl, HWCRC 4100 John R Detroit, Detroit, MI, 48201, USA. 3. Wayne State University, Detroit, MI, USA. 4. Christie Hospital NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. 5. Kaiser Permanente Medical Center, 2nd Floor, Hallway C, 975 Sereno Drive, Vallejo, CA, 94589, USA. 6. Chittaranjan National Cancer Institute, 37 Shyama Prasad Mukherjee Road, Bhawanipur, Kolkata, West Bengal, 700026, India. 7. ANCHOR Unit Clinic D, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZN, UK. 8. Shatabdi Super Specialty Hospital, Suyojit City Center, Mumbai Naka, Nashik, 422 005, India. 9. Tennessee Cancer Specialists, 1415 Old Weisgarser Road, Knoxville, TN, 37909-1292, USA. 10. Nektar Therapeutics, 455 Mission Bay Boulevard South, San Francisco, CA, 94158, USA. 11. UCLA Geffen School of Medicine, 201 S. Buena Vista Street, Suite 200, Burbank, CA, 91505, USA.
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.
RCT Entities:
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.
Entities:
Keywords:
Chemotherapy; Etirinotecan pegol; Irinotecan; KRAS mutant; Metastatic colorectal cancer
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