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Cancer Sci. 2020;111(2):513-527.

Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study.

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제1저자 방영주 · 교신저자 Chen Li-Tzong

PMID 31789476 PMC7004519 DOI 10.1111/cas.14264 IF 4.9 혈액종양내과
소속 (16)
  1. Seoul National University College of Medicine, Seoul, Korea.
  2. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
  3. National Yang-Ming University School of Medicine, Taipei, Taiwan.
  4. Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  5. China Medical University Hospital, Taichung, Taiwan.
  6. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  7. Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan.
  8. Korea University Guro Hospital, Seoul, Korea.
  9. Department of Hematology-Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan.
  10. Chonnam National University Hwasun Hospital, Gwangju, Korea.
  11. Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
  12. Severance Hospital, Yonsei University, Seoul, Korea.
  13. Ipsen Bioscience, Inc, Cambridge, Massachusetts, USA.
  14. National Institute of Cancer Research, National Health Research Institutes (NHRI), Tainan, Taiwan.
  15. Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
  16. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post-hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal-IRI+5-FU/LV (n = 34) had significantly longer median OS versus 5-FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal-IRI+5-FU/LV versus 5-FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal-IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5-FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal-IRI+5-FU/LV versus 5-FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506).

© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Keywords

Asian subgroupNAPOLI-1clinical trialliposomal irinotecanmetastatic pancreatic cancerphase 3

Figures

Figure 1
Figure 1 CONSORT diagram explaining the patient population included in this subgroup analysis (ITT population). 5‐FU, 5‐fluorouracil; LV, leucovorin (folinic acid); nal‐IRI, liposomal irinotecan; ITT, intention‐to‐treat
Figure 2
Figure 2 Kaplan‐Meier survival analyses in patients at centers in the Asia region. A, Overall survival (OS) with nal‐IRI+5‐FU/LV combination. B, OS with nal‐IRI monotherapy. C, Progression‐free survival (PFS) with nal‐IRI+5‐FU/LV combination. D, PFS with nal‐IRI monotherapy, all vs 5‐FU/LV controls (intention‐to‐treat [ITT] population). 5‐FU, 5‐fluorouracil; CI, confidence interval; HR, unstratified hazard ratio; LV, leucovorin (folinic acid); mo, months; nal‐IRI, liposomal irinotecan. Vertical bars indicate censoring points

그림 출처: PubMed Central 공개 논문 (PMC7004519)

Conflict of interest statement

Yung‐Jue Bang reports a consulting/advisory role for AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serono, Bayer, BMS, Eli Lilly, Taiho, Daiichi‐Sankyo, Astellas, BeiGene, GreenCross, Samyang Biopharm, Hanmi, Genexine, and Shire; research grants (to the institution for clinical trials) from AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serono, Bayer, BMS, GSK, Pfizer, Eli Lilly, Boehringer‐Ingelheim, MacroGenics, Boston Biomedical, FivePrime, Curis, Taiho, Takeda, Ono, Daiichi Sankyo, Astellas, BeiGene, Green Cross, CKD Pharma, and Genexine. Chung‐Pin Li reports no disclosures. Kyung‐Hun Lee reports an advisor role for AstraZeneca, Bayer, Eisai, Ono Pharmaceuticals, Roche and Samsung Bioepis; honoraria from AstraZeneca and Roche. Chang‐Fang Chiu reports no disclosures. Joon Oh Park reports an advisor role for Shire. Yan‐Shen Shan reports no disclosures. Jun Suk Kim reports no disclosures. Jen‐Shi Chen reports no disclosures. Hyun‐Jeong Shim reports no disclosures. Kun‐Ming Rau reports no disclosures. Hye Jin Choi reports no disclosures. Do‐Youn Oh reports an advisor/consultant role for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymework, and Shire; research grants from AstraZeneca, Novartis, Array, Eli Lilly, and Green Cross. Bruce Belanger was employed by Merrimack Pharmaceuticals, Inc., at the time of the study, and is currently an employee at Ipsen Bioscience, Inc. Li‐Tzong Chen reports honoraria from Eli Lilly, Novartis, Bristol‐Myers‐Squibb, Ono Pharmaceutical, TTY Biopharm, PharmaEngine, MSD, Syncore Bio, Five Prime, AstraZeneca, and Ipsen; a consultant or advisor role for Eli Lilly, Novartis, Bristol‐Myers‐Squibb, Ono Pharmaceutical, PharmaEngine, MSD, Five Prime, AstraZeneca; and research funding from Novartis, Merck Serono, TTY Biopharm, SynCoreBio, Polaris, Celgene, and Pfizer.

그 밖의 정보
출판 형태
Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial
저널
Cancer science · eISSN 1349-7006
전자 출판
2019-12-20
MeSH
Adenocarcinoma / drug therapy · Adult · Aged · Aged, 80 and over · Antineoplastic Combined Chemotherapy Protocols / administration & dosage / therapeutic use · Asian People · Endpoint Determination · Female · Fluorouracil / administration & dosage / therapeutic use · Humans · Irinotecan / administration & dosage / therapeutic use · Leucovorin / administration & dosage / therapeutic use · Liposomes · Male · Middle Aged · Neoplasm Metastasis · Pancreatic Neoplasms / drug therapy · Survival Analysis · Treatment Outcome
Substances
Liposomes · Irinotecan · Leucovorin · Fluorouracil
연구비
Merrimack Pharmaceuticals, Inc · Shire · Servier Global Medical Affairs
데이터
ClinicalTrials.gov: NCT01494506
참고문헌
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