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Clinical Trial
, 22 (1), 155-163

Peritoneal Metastasis as a Predictive Factor for Nab-Paclitaxel in Patients With Pretreated Advanced Gastric Cancer: An Exploratory Analysis of the Phase III ABSOLUTE Trial

Affiliations
Clinical Trial

Peritoneal Metastasis as a Predictive Factor for Nab-Paclitaxel in Patients With Pretreated Advanced Gastric Cancer: An Exploratory Analysis of the Phase III ABSOLUTE Trial

Atsuo Takashima et al. Gastric Cancer.

Abstract

Background: In the ABSOLUTE trial, weekly nanoparticle albumin-bound paclitaxel (w-nab-PTX) showed non-inferiority to weekly solvent-based paclitaxel (w-sb-PTX) for overall survival (OS). Thus, w-nab-PTX might be an option for second-line chemotherapy in advanced gastric cancer (AGC). However, predictive factors for efficacies of these agents have not been evaluated.

Methods: Patients previously enrolled in the ABSOLUTE trial were divided into apparent peritoneal metastasis group (PM group) and no apparent peritoneal metastasis group (no PM group) based on baseline imaging evaluated by RECIST ver. 1.1 criteria and amount of ascites. OS, progression-free survival, and overall response rate were compared between two arms in each group.

Results: This study included 240 and 243 patients in the w-nab-PTX and w-sb-PTX arms, respectively. In the PM group, the w-nab-PTX arm (n = 88) had longer OS than the w-sb-PTX arm (n = 103), and median survival time (MST) of 9.9 and 8.7 months [hazard ratio (HR) 0.63; 95% CI 0.45-0.88; P = 0.0060], respectively. In the no PM group, the w-nab-PTX arm (n = 140) had shorter OS than the w-sb-PTX arm (n = 152), and MST of 11.6 and 15.7 months (HR 1.40; 95% CI 1.06-1.86; P = 0.0180), respectively. After adjusting for prognostic factors, the HR for OS in the w-nab-PTX arm versus the w-sb-PTX arm was 0.59 (95% CI 0.42-0.83; P = 0.0023; PM group) and 1.34 (95% CI 1.01-1.78; P = 0.0414; no PM group), with significant interaction between treatment efficacy and presence of peritoneal metastasis (P = 0.0003).

Conclusions: The presence of apparent peritoneal metastasis might be a predictive factor for selecting w-nab-PTX for pretreated AGC patients.

Trial registration number: JapicCTI-132059.

Keywords: Nab-paclitaxel; Peritoneal metastasis; Predictive factor; Second-line chemotherapy; Solvent-based paclitaxel.

Conflict of interest statement

Conflict of interest

KS reports personal fees from Astellas, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, Abbvie and Yakult, grants and personal fees from Lilly and Ono Pharma, grants from Sumitomo Dainippon Pharma, MSD, Daiichi-Sankyo, Taiho Pharma and Chugai Pharma outside the submitted work. HH reports grants from AstraZeneca, Daiichi-Sankyo, Sumitomo Dainippon Pharma, Lilly, Merck Serono, MSD, Ono Pharma, Taiho Pharma, Chugai Pharma, Boehringer Ingelheim, Eisai, LSK BioPharma, Incyte and Pfizer outside the submitted work. SH reports personal fees from Lilly and Taiho Pharma outside the submitted work. KN reports grants and non-financial support from Taiho Pharma during the conduct of the study, and personal fees from Taiho Pharma, Chugai Pharma, Yakult, Lilly, Ajinomoto Pharma outside the submitted work. KA reports other from Taiho Pharma during the conduct of the study, and other from MSD outside the submitted work. KM reports grants from Ono Pharma, MSD, Daiichi-Sankyo, Kyowa Hakko Kirin, Shionogi Pharma and Gilead Sciences, and personal fees from Chugai Pharma, Taiho Pharma, Takeda, Merck Serono, Lilly and Yakult outside the submitted work. TE reports grants and personal fees from Lilly, Taiho Pharma, Merck Serono and Ono Pharma, grants from Novartis, Daiichi-Sankyo, Sumitomo Dainippon Pharma, AstraZeneca, Boehringer Ingelheim and MSD, and personal fees from Chugai Pharma, Nippon Kayaku and Eisai outside the submitted work. TT reports grants and personal fees from Taiho Pharma during the conduct of the study, and personal fees from Daiichi-Sankyo, Kyowa Hakko Kirin and Eisai, grants and personal fees from Chugai Pharma and Novartis, and grants from Takeda, Ono Pharma, MSD and Merck Serono outside the submitted work. AS reports personal fees from Taiho Pharma outside the submitted work. MG reports grants, personal fees and non-financial support from Taiho Pharma during the conduct of the study, grants, personal fees and non-financial support from Ono Pharma, Yakult, Chugai Pharma, Kyowa Hakko Kirin and Mochida Pharma, personal fees and non-financial support from Takeda, Novartis, and Bayer outside the submitted work. NM reports grants from Taiho Pharma during the conduct of the study, and grants from Ono, MSD and Lilly outside the submitted work. NB reports grants from Taiho Pharma during the conduct of the study, and grants and personal fees from Taiho Pharma and Bristol-Myers Squibb outside the submitted work. MS reports personal fees from Taiho Pharma outside the submitted work. SM reports personal fees from Taiho Pharma during the conduct of the study, and personal fees from Bristol-Myers Squibb outside the submitted work. WK reports grants, personal fees and non-financial support from Taiho Pharma during the conduct of the study. All remaining authors have no conflicts of interest to declare.

Human rights statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.

Informed consent

All patients provided written informed consent.

Figures

Fig. 1
Fig. 1
Kaplan–Meier plot of overall survival by subgroup (4-group version). Group A: patients with no detectable peritoneal lesions and no massive ascites, group B: patients with detectable peritoneal lesions and no massive ascites, group C: patients with no detectable peritoneal lesions and massive ascites, group D: patients with detectable peritoneal lesions and massive ascites. w-nab-PTX weekly nanoparticle-bound paclitaxel, w-sb-PTX weekly solvent-based paclitaxel, OS overall survival
Fig. 2
Fig. 2
Kaplan–Meier plot of overall survival and progression-free survival for the reclassified subgroup (2-group version). a Progression-free survival. b Overall survival. w-nab-PTX weekly nanoparticle-bound paclitaxel, w-sb-PTX weekly solvent-based paclitaxel, PM group the apparent peritoneal metastasis group, no PM group the no apparent peritoneal metastasis group, PFS progression-free survival, OS overall survival

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