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Retrospective study of regorafenib and trifluridine/tipiracil efficacy as a third-line or later chemotherapy regimen for refractory metastatic colorectal cancer.

ABSTRACT: Regorafenib and trifluridine/tipiracil (TAS-102) are novel antitumor agents for patients with refractory metastatic colorectal cancer. However, it is unclear which patients may derive a survival benefit from these drugs in real-life clinical practice. We evaluated retrospectively the efficacy and safety of regorafenib and TAS-102 at a single institution between June 2013 and November 2015. Cox regression analysis was carried out to obtain predictive scores (the nearest integers of hazard ratio) for survival benefit. Forty-four patients treated with regorafenib or TAS-102 were included in the analysis; among them, 17 received crossover treatment. The median overall survival (OS) was 9.1 months for regorafenib and 9.3 months for TAS-102, and the corresponding values after crossover were 7.1 and 5.3 months, respectively. OS was not correlated to relative dose intensity, but was proportional to the total administered dose of each drug. Adverse events were tolerable even after crossover. We identified three variables as significant for prediction of OS with good discrimination (C-statistic=0.70): Poor Eastern Cooperative Oncology Group performance status, time since diagnosis of metastatic disease ?18 months, and previous chemotherapy continued ?2 months beyond progression were all predictors of poor OS. Regorafenib and TAS-102 can be recommended for patients with better performance status and slow progression of metastatic disease. Optimal survival benefit was provided by prompt administration of either drug after failure of previous chemotherapy, with flexible titration to the optimal dose for each individual patient.

SUBMITTER: Tanaka A

PROVIDER: S-EPMC6176362 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Retrospective study of regorafenib and trifluridine/tipiracil efficacy as a third-line or later chemotherapy regimen for refractory metastatic colorectal cancer.

Tanaka Akira A Sadahiro Sotaro S Suzuki Toshiyuki T Okada Kazutake K Saito Gota G Miyakita Hiroshi H

Oncology letters 20180907 5

Regorafenib and trifluridine/tipiracil (TAS-102) are novel antitumor agents for patients with refractory metastatic colorectal cancer. However, it is unclear which patients may derive a survival benefit from these drugs in real-life clinical practice. We evaluated retrospectively the efficacy and safety of regorafenib and TAS-102 at a single institution between June 2013 and November 2015. Cox regression analysis was carried out to obtain predictive scores (the nearest integers of hazard ratio) ...[more]

PMID: 30344762

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Project description:BackgroundTrifluridine/tipiracil (FTD/TPI) and regorafenib prolong survival for patients with refractory metastatic colorectal cancer (mCRC); limited comparative effectiveness data exist.Materials and methodsA retrospective, longitudinal cohort study of patients with mCRC who initiated FTD/TPI or regorafenib (index therapy) between 2012 and 2017 at a U.S. tertiary oncology center, Dana-Farber Cancer Institute, was conducted. Using best tumor response assessments, real-world overall response rates (rwORR) and disease control rates (rwDCR) were described and analyzed using logistic regression. Survival rate was examined for each month after index therapy using Kaplan-Meier. Overall survival (OS) was assessed using Cox proportional hazards models. Subgroup analyses among patients with index therapy as second- or third-line were performed.ResultsOne hundred twenty-six and 95 patients were treated with FTD/TPI or regorafenib as index therapy, respectively. Patients treated with FTD/TPI versus regorafenib had a better response (rwORR 52.5% vs. 34.2%; adjusted odds ratio [OR] = 2.6; all p value <.05; rwDCR 64.2% vs. 46.1%; adjusted OR = 2.5; all p value <.05). Similar findings were observed for FTD/TPI versus regorafenib as second- or third-line therapy (rwORR 54.8% vs. 25.9%; adjusted OR = 4.1; all p value <.05; rwDCR 69.0% vs. 37.0%; adjusted OR = 4.9; all p value <.05). A greater proportion of patients treated with FTD/TPI versus regorafenib survived at 3 months (86.2% vs. 73.4%; p value = .016) and 4 months (79.6% vs. 65.8%; p value = .017). Adjusted OS hazard ratio for FTD/TPI versus regorafenib was 0.80, p value = .157.ConclusionPatients treated with FTD/TPI had better tumor response and disease control than patients treated with regorafenib. Subgroup analysis in second- or third-line suggests that early use of FTD/TPI may have clinical benefits.Implications for practiceIn this retrospective cohort study, patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil (FTD/TPI) were significantly less likely than those treated with regorafenib to have dose modifications and more likely to have higher real-world objective response rate (rwORR) and real-world disease control rate (rwDCR) while treated. Patients treated with FTD/TPI versus regorafenib had significantly higher odds of having rwORR or rwDCR in adjusted analyses. Monthly survival rates were higher overall in patients treated with FTD/TPI versus regorafenib in the first 6 months of follow-up, particularly at months 3 and 4. This study offers insight into patients' treatment experience in real-world clinical settings.

Project description:BackgroundThis study compared the efficacy of regorafenib and trifluridine/tipiracil (TFTD) in patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy, because despite their clinical approval, it still remains unclear which of these two drugs should be used as initial treatment.Materials and methodsThe clinical data of patients with mCRC who were treated with regorafenib or TFTD and those of drug-naive patients, between June 2014 and September 2015, were retrospectively collected from 24 institutions in Japan. Overall survival (OS) was evaluated using the Cox's proportional hazard models based on propensity score adjustment for baseline characteristics.ResultsA total of 550 patients (223 patients in the regorafenib group and 327 patients in the TFTD group) met all criteria. The median OS was 7.9 months (95% confidence interval [CI], 6.8-9.2) in the regorafenib group and 7.4 months (95% CI, 6.6-8.3) in the TFTD group. The propensity score adjusted analysis showed that OS was similar between the two groups (adjusted hazard ratio [HR], 0.96; 95% CI, 0.78-1.18). In the subgroup analysis, a significant interaction with age was observed. Regorafenib showed favorable survival in patients aged <65 years (HR, 1.29; 95% CI, 0.98-1.69), whereas TFTD was favored in patients aged ≥65 years (HR, 0.78; 95% CI, 0.59-1.03).ConclusionNo significant difference in OS between regorafenib and TFTD was observed in patients with mCRC. Although the choice of the drug by age might affect survival, a clearly predictive biomarker to distinguish the two drugs should be identified in further studies.Implications for practicePrevious studies of patients with metastatic colorectal cancer refractory to standard chemotherapy had demonstrated that both regorafenib and trifluridine/tipiracil could result in increased overall survival compared with placebo, but there are no head-to-head trials. This large, multicenter, observational study retrospectively compared the efficacy of regorafenib and trifluridine/tipiracil in 550 patients with metastatic colorectal cancer refractory to standard chemotherapy who had access to both drugs. Although no difference in overall survival was found between the two drugs in adjusted analysis using propensity score, regorafenib showed favorable survival in patients aged <65 years, whereas trifluridine/tipiracil was favored in patients aged ≥65 years in the subgroup analysis.

Project description:BACKGROUND:Angiogenesis is critical to gastroesophageal adenocarcinoma growth and metastasis. Regorafenib is a multikinase inhibitor targeting angiogenic and stromal receptor tyrosine kinases. We evaluated whether regorafenib augments the antitumor effect of first-line chemotherapy in metastatic esophagogastric cancer. MATERIALS AND METHODS:Patients with previously untreated metastatic gastroesophageal adenocarcinoma received 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) every 14?days and regorafenib 160 mg daily on days 4 to 10 of each 14-day cycle. The primary endpoint was 6-month progression-free survival (PFS). To identify predictive biomarkers of outcome, we examined correlations between genomic characteristics of sequenced pretreatment tumors and PFS. RESULTS:Between August 2013 and November 2014, 36 patients with metastatic esophagogastric cancer were accrued to this single-center phase II study (NCT01913639). The most common grade 3-4 treatment-related adverse events were neutropenia (36%), leucopenia (11%) and hypertension (8%). The 6-month PFS was 53% (95% confidence interval [CI], 38%-71%), the objective response rate was 54% (95% CI, 37%-70%), and the disease control rate was 77% (95% CI, 67%-94%). Next-generation sequencing did not identify any genomic alterations significantly correlated with response, and there was no association between homologous recombination deficiency and PFS with platinum-based chemotherapy. CONCLUSION:Regorafenib (one week on-one week off schedule) is well tolerated in combination with first-line FOLFOX but does not improve 6-month PFS relative to historical control. IMPLICATIONS FOR PRACTICE:Prognosis for metastatic esophagogastric cancer remains poor despite modern systemic therapy regimens. This phase II trial indicates that the combination of regorafenib and FOLFOX is well tolerated but does not add to the efficacy of first-line chemotherapy in metastatic esophagogastric cancer. Notably, recently reported data suggest potential synergy between regorafenib and the PD-1 inhibitor nivolumab. As this study demonstrates that regorafenib plus FOLFOX is safe, and combined chemotherapy and immunotherapy show favorable toxicity profiles, future studies combining immunotherapy with regorafenib and chemotherapy may be feasible.

Dataset Information

Retrospective study of regorafenib and trifluridine/tipiracil efficacy as a third-line or later chemotherapy regimen for refractory metastatic colorectal cancer.

Publications

Retrospective study of regorafenib and trifluridine/tipiracil efficacy as a third-line or later chemotherapy regimen for refractory metastatic colorectal cancer.

Similar Datasets

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