The Efficacy and Safety of Trifluridine/Tipiracil Treatment for Elderly Patients With Metastatic Colorectal Cancer in a Real-world Setting

620 Background: Activating B-type Raf kinase (BRAF) mutations, mostly missense V600E, occur in approximately 8% to 12% of patients with metastatic colorectal cancer (mCRC). BRAF (V600E)mt is a strong predictor of a poor prognosis, with distinct clinical and pathological features. However, it is unknown whether this mutation is predictive of any treatment benefit in a real world setting. Methods: We conducted an observational, retrospective, multicentric study of patients with BRAF V600E-mt mCRC treated at nine university Spanish hospitals in NW Spain, belonging to GITuD (Galician Research Group on Digestive Tumors). Demographic, clinic and pathological characteristics, overall survival (OS) and first-line progression free survival (PFS) were retrospectively collected and analyzed. Results: Data from 65 patients treated between November 2010 to June 2018 were recorded in this study. Median age was 62.8 years (range 30-83 years), 55.4 % female, 75.4% ECOG PS0-1, 49.2% right-sided, 35.2% high grade, 69.2% synchronous presentation, 66.2% primary tumor resection and median metastatic locations was 2 (range 1-5). With a median follow up of 64.6 months, median OS was 12.9 months (95% CI, 9.8-16.0 months) and first line PFS was 4.1 months (95% CI, 2.7-5.5 months). First line PFS according treatment: Bev+Triplet-CT/Bev+Doublet-CT/antiEGFR+Doublet-CT/Doublet-CT: 6.2 vs 4.8 vs 2.9 vs 2.1 months (p = 0.020). Bevacizumab based chemotherapy was associated with a prolonged first line PFS (median 5.0 vs. 2.1 months, HR, 0.406; 95% CI, 0.20-0.81; p = 0.005). Nevertheless, no statistical differences between bevacizumab based regimes, (Triplet-CT vs Doublet-CT (HR 0.830; 95% CI 0.4-1.9; p = 0.666)) or between Doublet-CT with or without a antiEGFR were found (HR 0.511; 95% CI 0.2-1.6; p = 0.223). Conclusions: Our study confirms the negative prognostic impact of BRAF V600Emt in mCRC and encourage the use of anti-angiogenic based chemotherapy in this subgroup of patients.

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Validation of cost-effectiveness of trifluridine/tipiracil versus best supportive care and regorafenib for previously treated metastatic colorectal cancer in the UK using phase IIIb PRECONNECT early access clinical trial data in the real world setting.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.639 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 639-639

Author(s):

Javier Sabater ◽

Lewis Ralph ◽

Rachael Batteson ◽

Grant McCarthy ◽

Jaro Wex ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Cost Effectiveness ◽

Supportive Care ◽

Metastatic Colorectal Cancer ◽

Real World ◽

Best Supportive Care ◽

Real World Setting ◽

Phase Iiib ◽

Previously Treated

639 Background: Trifluridine/tipiracil (FTD/TPI) is indicated and recommended for the treatment of previously treated metastatic colorectal cancer (mCRC). Previous evaluations used pooled clinical evidence from the Phase III (RECOURSE) and Phase II trials to model cost-effectiveness, but FTD/TPI specific utilities were not available and alternative data sources were used. The aim of this study was to utilize EQ-5D data from an ongoing Phase IIIb trial (PRECONNECT) within an updated cost-effectiveness model to validate health-related quality of life (HRQoL) outcomes for mCRC patients receiving FTD/TPI. Methods: EQ-5D-3L data from PRECONNECT trial were analyzed with UK utility tariff applied. Pre- and post-progression health state utilities were estimated using a linear mixed effects regression model. Indirect comparison versus regorafenib was based on evidence from the CORRECT trial. Utilities and UK costs (GBP, 2018) were then implemented into the existing economic model. Results: Mean pre-progression and post-progression utilities were 0.72 and 0.59, respectively, with discounted incremental quality adjusted life years gain of 2.1 months versus best supportive care (BSC) and 0.8 versus regorafenib. Use of FTD/TPI based on PRECONNECT data, as in the previous analysis, was associated with improved mean survival pre-progression (by 1.8 months) and post-progression (by 1.4 months) for the total OS gain of 3.2 months versus BSC. The mean OS gain versus regorafenib was 1.4 months. Updated cost-effectiveness analysis using PRECONNECT derived inputs showed that results remained broadly unchanged with a negligible increase in ICER from £51,589 to £51,792 (£51,101 in the probabilistic sensitivity analysis) when compared to BSC, while FTD/TPI remained dominant (more effective and less costly) versus regorafenib. Conclusions: New HRQoL data from the PRECONNECT study collected in a real-world setting validated previous HRQoL inputs used to model cost-effectiveness of FTD/TPI in previously treated metastatic colorectal cancer. Clinical trial information: NCT03306394.

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Survival impact on regorafenib (REG) and trifluridine/tipiracil hydrochloride (FTD/TPI) for patients with metastatic colorectal cancer: Single institutional experience.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.43 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 43-43

Author(s):

Keigo Chida ◽

Daisuke Kotani ◽

Kentaro Sawada ◽

Yoshiaki Nakamura ◽

Akihito Kawazoe ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Real World ◽

Phase Iii ◽

First Line ◽

Standard Chemotherapy ◽

Exon 2 ◽

The Real ◽

Real World Setting ◽

Tipiracil Hydrochloride

43 Background: Regorafenib (REG) and trifluridine/tipiracil hydrochloride (FTD/TPI) demonstrated overall survival (OS) benefit in patients (pts) with metastatic colorectal cancer (mCRC) in the CORRECT and RECOURSE phase III trials. In Japan, REG and FTD/TPI have been approved in 2013 and 2014, respectively. However, little is known about survival impact on these agents in the real-world setting. Therefore, the aim of this retrospective study was to evaluate the effects of REG and FTD/TPI in pts with mCRC. Methods: We collected medical records from consecutive 1142 pts who had been initiated with first-line chemotherapy for mCRC from 2008 to 2016 at National Cancer Center Hospital East. The survival outcomes were compared between pts from 2008 to 2011 (cohort A) and those from 2012 to 2016 (cohort B). This study excluded pts who have not been refractory or intolerant to standard chemotherapy including fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR antibody if KRAS exon 2/ RAS wild-type tumors. Results: A total of 590 pts were analyzed (cohort A; N = 236 and cohort B; N = 354). More patients received at least one of REG or FTD/TPI in cohort B (16.1% vs. 59.9%, p < 0.001). The time from initiation to end of standard chemotherapy was comparable between the two cohort (20.0 vs. 17.5 months, p = 0.266). With a median follow-up period of 34.9 months, salvage-line OS (sOS) after standard chemotherapy was significantly longer in cohort B (4.8 vs. 6.6 months, p = 0.001), while there was only a favorable trend in cohort B in terms of OS from start of first-line treatment (27.3 vs. 28.5 months, p = 0.516). In cohort B, pts who sequentially received both of REG and FTD/TPI showed longest sOS (median, both of REG and FTD/TPI; 11.3 months, either REG or FTD/TPI; 7.0 months, neither REG nor FTD/TPI; 3.1 months). Conclusions: Our study showed that REG and FTD/TPI led to prolongation of sOS in the real-world setting, indicating the importance of strategies which make all active agents available to pts with mCRC.

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