Makoto Ueno1, Shoji Nakamori2, Kazuya Sugimori3, Masashi Kanai4, Masafumi Ikeda5, Masato Ozaka6, Masayuki Furukawa7, Takuji Okusaka8, Ken Kawabe9, Junji Furuse10, Yoshito Komatsu11, Hiroshi Ishii12, Atsushi Sato13, Satoshi Shimizu14, Priti Chugh15, Rui Tang15, Tatsuya Ioka16. 1. Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama-shi, Kanagawa, Japan. 2. Department of Surgery, NHO Osaka National Hospital, Osaka, Japan. 3. Gastroenterological Center, Yokohama City University Medical Center, Yokohama-shi, Kanagawa, Japan. 4. Department of Medical Oncology, Kyoto University Hospital, Kyoto, Japan. 5. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan. 6. Department of Gastroenterology, Cancer Institute Hospital of JFCR, Tokyo, Japan. 7. Department of Hepatic-biliary-pancreatology, NHO Kyushu Cancer Center, Fukuoka, Japan. 8. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. 9. Department of Medicine and Bioregulatory Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 10. Faculty of Medicine, Department of Medical Oncology, Kyorin University, Tokyo, Japan. 11. Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Hokkaido, Japan. 12. Clinical Research Center, Chiba Cancer Center, Chiba, Japan. 13. Department of Oncology, Hirosaki University Hospital, Aomori, Japan. 14. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. 15. Servier Pharmaceuticals, Boston, MA, USA. 16. Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.
Abstract
BACKGROUND: In the NAPOLI-1 phase 3 trial, liposomal irinotecan (nal-IRI) +5-fluorouracil/leucovorin (5-FU/LV) significantly increased mPFS versus 5-FU/LV (3.1 vs. 1.5 months [unstratified HR = 0.56, p = 0.0001]) in patients with mPAC that progressed on prior gemcitabine-based therapy. This randomized phase 2 trial evaluated nal-IRI+5-FU/LV tolerability (Part 1), safety, and efficacy (Part 2; outcomes reported here) in Japanese patients with mPAC that progressed on gemcitabine-based therapy. METHODS: Patients were randomized 1:1 and stratified by KPS (70 and 80 vs. ≥90) and baseline albumin (≥4.0 g/dl vs. <4.0 g/dl). Primary endpoint was PFS; secondary endpoints were ORR, DCR, OS, TTF, CA19-9 response, and QoL. The ITT population comprised all randomized patients. RESULTS: Patient characteristics differed between nal-IRI+5-FU/LV (n = 40) and 5-FU/LV (n = 39) arms, including baseline hepatic lesions (63% vs. 51%), stage IV disease at diagnosis (78% vs. 51%), and post-study anticancer therapy (55% vs. 72%). Investigator-assessed mPFS increase with nal-IRI+5-FU/LV was clinically meaningful and statistically significant versus 5-FU/LV (2.7 vs. 1.5 months, HR = 0.60). Independently assessed mPFS showed similar trends (1.7 vs. 1.6 months, HR = 0.79). mOS was 6.3 months with nal-IRI+5-FU/LV and not reached with 5-FU/LV. ORR increased significantly with nal-IRI+5-FU/LV versus 5-FU/LV (18% vs. 0, rate difference 17.5). Commonly reported grade ≥3 treatment-emergent AEs were decreased neutrophil count (37% vs. 3%), decreased white blood cell count (20% vs. 0), and diarrhea (17% vs. 3%). CONCLUSIONS: In conclusion, clinically meaningful and statistically significant gains in investigator-assessed PFS and ORR were observed with nal-IRI+5-FU/LV versus 5-FU/LV in Japanese patients, with no new or unexpected safety signals. (Clinicaltrials.gov ID: NCT02697058).
RCT Entities:
BACKGROUND: In the NAPOLI-1 phase 3 trial, liposomal irinotecan (nal-IRI) +5-fluorouracil/leucovorin (5-FU/LV) significantly increased mPFS versus 5-FU/LV (3.1 vs. 1.5 months [unstratified HR = 0.56, p = 0.0001]) in patients with mPAC that progressed on prior gemcitabine-based therapy. This randomized phase 2 trial evaluated nal-IRI+5-FU/LV tolerability (Part 1), safety, and efficacy (Part 2; outcomes reported here) in Japanese patients with mPAC that progressed on gemcitabine-based therapy. METHODS:Patients were randomized 1:1 and stratified by KPS (70 and 80 vs. ≥90) and baseline albumin (≥4.0 g/dl vs. <4.0 g/dl). Primary endpoint was PFS; secondary endpoints were ORR, DCR, OS, TTF, CA19-9 response, and QoL. The ITT population comprised all randomized patients. RESULTS:Patient characteristics differed between nal-IRI+5-FU/LV (n = 40) and 5-FU/LV (n = 39) arms, including baseline hepatic lesions (63% vs. 51%), stage IV disease at diagnosis (78% vs. 51%), and post-study anticancer therapy (55% vs. 72%). Investigator-assessed mPFS increase with nal-IRI+5-FU/LV was clinically meaningful and statistically significant versus 5-FU/LV (2.7 vs. 1.5 months, HR = 0.60). Independently assessed mPFS showed similar trends (1.7 vs. 1.6 months, HR = 0.79). mOS was 6.3 months with nal-IRI+5-FU/LV and not reached with 5-FU/LV. ORR increased significantly with nal-IRI+5-FU/LV versus 5-FU/LV (18% vs. 0, rate difference 17.5). Commonly reported grade ≥3 treatment-emergent AEs were decreased neutrophil count (37% vs. 3%), decreased white blood cell count (20% vs. 0), and diarrhea (17% vs. 3%). CONCLUSIONS: In conclusion, clinically meaningful and statistically significant gains in investigator-assessed PFS and ORR were observed with nal-IRI+5-FU/LV versus 5-FU/LV in Japanese patients, with no new or unexpected safety signals. (Clinicaltrials.gov ID: NCT02697058).
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