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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.

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.

SUBMITTER: Takashima A

PROVIDER: S-EPMC6315007 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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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.

Takashima Atsuo A Shitara Kohei K Fujitani Kazumasa K Koeda Keisuke K Hara Hiroki H Nakayama Norisuke N Hironaka Shuichi S Nishikawa Kazuhiro K Kimura Yutaka Y Amagai Kenji K Fujii Hirofumi H Muro Kei K Esaki Taito T Choda Yasuhiro Y Takano Toshimi T Chin Keisho K Sato Atsushi A Goto Masahiro M Fukushima Norimasa N Hara Takuo T Machida Nozomu N Ohta Manabu M Boku Narikazu N Shimura Masashi M Morita Satoshi S Koizumi Wasaburo W

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20180531 1

<h4>Background</h4>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.<h4>Methods</h4>Patients previously enrolled in the ABSOLUTE trial were divided into apparent peritoneal metastasis group (P ...[more]

PMID: 29855738

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Project description:BACKGROUND:Mesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear. SUBJECTS, MATERIALS, AND METHODS:Mesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition. RESULTS:High mesothelin expression was observed in 49.7% of patients and significantly associated with high pathologic T (p = .021) and peritoneal recurrence (p = .018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p = .001), OS (p = .001), and peritoneal recurrence (p = .002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p = .013) and diffuse/mixed type gastric cancer (p = .010). CONCLUSION:High mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer. IMPLICATIONS FOR PRACTICE:This study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.

Dataset Information

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.

Publications

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.

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