Combination chemotherapy with TAS-102 plus bevacizumab in salvage-line treatment of metastatic colorectal cancer: A single-center, retrospective study examining the prognostic value of the modified Glasgow Prognostic Score in salvage-line therapy of metastatic colorectal cancer.

Abstract

The combination regimen of TAS-102, a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, with bevacizumab (C-TASK FORCE), a selective monoclonal antibody inhibitor of vascular endothelial growth factor-A, as salvage-line therapy for metastatic colorectal cancer (mCRC) was established based on its high clinical effectiveness. The aim of the present study was to evaluate the prognostic accuracy of the modified Glasgow Prognostic Score (mGPS) in patients receiving TAS-102 plus bevacizumab. The study included 17 patients (12 men and 5 women, mean age 60.4±13.4 years) with unresectable mCRC who were confirmed to have wild-type or mutant RAS genes. The patients received salvage-line treatment with TAS-102 plus bevacizumab at the Surgical Oncology Department of Gifu University School of Medicine between March 2016 and August 2018. The study population was heavily pretreated; the majority of the patients (71%) had received ≥4 prior regimens and, in addition to fluoropyrimidine, irinotecan and oxaliplatin, all had received bevacizumab (100%) and either cetuximab or panitumumab (47%). The RAS status was wild-type in 9 (53%) and mutant in 8 (47%) patients. The primary tumor locations included the right-sided colon in 5 patients (29%; cecum in 2 and transverse colon in 3 cases) and left-sided colorectum in 12 patients [71%; sigmoid colon in 4, rectosigmoid (Rs) in 4, and rectum above/below the peritoneal reflection (Ra/b) in 4 cases]. Metastatic sites included the liver in 15 (88%), lung in 13 (76%), lymph nodes in 7 (41%), and peritoneal dissemination in 5 (24%) patients. The number of metastatic sites was 1 in 3 (18%) and >2 in 14 (82%) patients. Their first staging imaging scans (after 2 cycles of therapy) were available for review in all 17 patients. At first evaluation, 5 (29%) patients had progressive disease (PD), 12 (71%) had stable disease, and none had a partial response to TAS-102 plus bevacizumab. The median overall survival (OS) of 14.1 months and progression-free survival (PFS) of 6.8 months were comparable to the 11.2 and 5.6 months, respectively, in the C-TASK FORCE study. Upon considering three groups, namely mGPS 0, mGPS 1 and mGPS 2, the median PFS times were significantly different (mGPS 0 vs. mGPS 2, P=0.02; and mGPS 1 vs. mGPS 2, P=0.06). The median PFS times in the mGPS 0, 1 and 2 groups were 12.1, 4.8 and 2.3 months, respectively. Median OS was also significantly different (mGPS 0 vs. mGPS 2, P=0.01; and mGPS 1 vs. mGPS 2, P=0.04). The median OS times in the mGPS 0, 1 and 2 groups were 14.0, not reached, and 2 months, respectively. The present study demonstrated the efficacy and safety of the TAS-102 plus bevacizumab combination as salvage-line treatment. This combination therapy (the TAS-102 plus bevacizumab) has obtained valid results with PFS OS as well as C-TASK.FORCE study. The results of the present study also confirmed the prognostic accuracy of mGPS in salvage-line treatment of patients with mCRC.

• Authors: Nobuhisa Matsuhashi, Takao Takahashi, Hironori Fujii, Tomonari Suetsugu, Masahiro Fukada, Yoshinori Iwata, Yoshihisa Tokumaru, Takeharu Imai, Ryutaro Mori, Toshiyuki Tanahashi, Satoshi Matsui, Hisashi Imai, Yoshihiro Tanaka, Kazuya Yamaguchi, Manabu Futamura, Kazuhiro Yoshida
• Journal: Molecular and clinical oncology (Mol Clin Oncol) Vol. 11 Issue 4 Pg. 390-396 (Oct 2019) ISSN: 2049-9450 [Print] England
• PMID: 31475067 (Publication Type: Journal Article)