Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study

Moriwaki, Toshikazu; Fukuoka, Shota; Taniguchi, Hiroya; Takashima, Atsuo; Kumekawa, Yusuke; Kajiwara, Takeshi; Yamazaki, Kentaro; Esaki, Taito; Makiyama, Chinatsu; Denda, Tadamichi; Satake, Hironaga; Suto, Takeshi; Sugimoto, Naotoshi; Enomoto, Masanobu; Ishikawa, Toshiaki; Kashiwada, Tomomi; Shimada, Masahiko; Komatsu, Yoshito; Okuyama, Hiroomi; Baba, Eishi; Sakai, Daisuke; Watanabe, Tomoki; Tamura, Takao; Yamashita, Kimihiro; Gosho, Masahiko; Shimada, Yasuhiro

doi:10.1634/theoncologist.2017-0275

Cited by 91 publications

(97 citation statements)

References 20 publications

(35 reference statements)

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“…The reasons for these differences are unclear but may reflect differing clinical practice in the evaluation and recording of ECOG-PS scores in different countries, or may suggest that patients included in the German and UK NPPs were at a more advanced stage of disease at enrolment. The number and type of previous treatments observed were similar to those reported in observational studies from the Netherlands [14], Japan [15], Latvia [16] and Germany [17]. However, a smaller proportion of the patients receiving trifluridine/tipiracil in this analysis had at least 4 prior treatment regimens (19%) than in the RE-COURSE trial [10] (60%).…”

Section: Discussionsupporting

confidence: 80%

“…This is broadly consistent with expectations based on the progression-free survival reported in the RECOURSE trial (2.0 months) [ [24] publications, though less than the progression-free survival reported by Skuja et al (5.0, [95% CI: 4.09-5.90] months), though the authors noted the small sample size (n = 14) was a limitation [16]. The tolerability profile of trifluridine/ tipiracil was consistent with that previously reported; rates of adverse events were broadly consistent with existing literature, with neutropenia occurring in approximately 30% of patients [14,15,17,23,25].…”

Section: Discussionsupporting

confidence: 79%

“…The demographics and clinical characteristics of patients enrolled in the NPP who went on to receive at least one dose of trifluridine/ tipiracil were broadly similar to those not receiving trifluridine/tipiracil. Furthermore, patients enrolled had similar demographic characteristics (median age, sex) to those in the RECOURSE trial [10] and several real-world studies [13][14][15][16]. However, there was a higher proportion of patients in the RECOURSE trial [10] and the Italian single-centre compassionate use programme (CUP) [13] with ECOG-PS scores of 0 (56 and 63% respectively) than patients enrolled in the UK NPP (28% of patients receiving ≥1 dose of trifluridine/tipiracil, 14% of patients not receiving trifluridine/tipiracil).…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent post-hoc analysis of RECOURSE trial data has demonstrated the clinical efficacy and tolerability of trifluridine/tipiracil in various subgroups [11] and clinically meaningful improvements in quality-adjusted survival [12]. There is further evidence supporting the clinical effectiveness and tolerability of trifluridine/tipiracil in various geographies [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 97%

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Review of metastatic colorectal cancer treatment pathways and early clinical experience of trifluridine/tipiracil in the UK named patient programme

Iveson

Carter²,

Shiu

et al. 2020

BMC Cancer

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Background: The standard first-and second-line chemotherapy backbone regimens for metastatic colorectal cancer (mCRC) are 5-fluorouracil (5-FU)/capecitabine-based with addition of irinotecan or oxaliplatin. Until recently, evidence for optimal sequencing post second-line was sparse. Trifluridine/tipiracil (indicated for mCRC and gastric cancer after standard chemotherapies) was made available to UK patients via a named patient programme (NPP) before receiving marketing authorisation in Europe in 2016, allowing characterisation of UK treatment pathways, and evaluation of trifluridine/tipiracil in a UK non-trial population.Methods: Data collected routinely for the NPP were analysed to describe the patient demographics, clinical characteristics and treatment pathways. Patients eligible for the programme were adults (≥18 years) with histologically or cytologically confirmed mCRC who had previously received chemotherapy treatment(s).Results: Of the 250 eligible patients enrolled in the NPP, 194 patients received ≥1 dose of trifluridine/tipiracil and 56 patients did not receive trifluridine/tipiracil. The following results are reported first for patients who received trifluridine/tipiracil and second for those who did not receive trifluridine/tipiracil: median (IQR) age was 63.0 (54.0-69.0) and 62.0 (54.8-69.0) years; Eastern Cooperative Oncology Group performance status score was 0 for 28 and 14%, 1 for 65 and 70%, 2 for 7 and 16%. In terms of previous systemic treatments 47 and 43% had 2 prior lines of therapy. FOLFOX-, FOLFIRI-and CAPOX-based therapies were the most common first-line regimens in patients receiving trifluridine/tipiracil (37, 35 and 21%, respectively), and in patients not receiving trifluridine/tipiracil (41, 30 and 20%, respectively). Second-line treatment regimens in patients receiving and not receiving trifluridine/tipiracil were most commonly FOLFIRI-based (48 and 41%, respectively) and respectively). Patients received a median of 2 cycles of trifluridine/tipiracil with a median treatment duration of 1.8 (95% CI: 1.8-2.4) months. In patients who discontinued treatment due to disease progression, the median progression-free duration was 2.8 (95% CI: 2.4-2.9) months. Conclusions:The results highlight the number of treatment pathways used to treat mCRC in routine UK clinical practice prior to the marketing authorisation and National Institute for Health and Care Excellence approval of trifluridine/tipiracil and highlight the lack of clinical guidelines for mCRC.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Review of metastatic colorectal cancer treatment pathways and early clinical experience of trifluridine/tipiracil in the UK named patient programme

Iveson

Carter²,

Shiu

et al. 2020

BMC Cancer

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“…The proportion of patients who required dose modifications or discontinued treatment due to toxicities was lower with trifluridine/tipiracil than regorafenib 25 . Observational studies conducted in Japan have shown similar efficacy but different toxicity profiles with regorafenib versus trifluridine/tipiracil in patients with mCRC refractory to standard chemotherapy 26‐28 …”

Section: Practical Guidancementioning

confidence: 99%

Trifluridine/tipiracil: A practical guide to its use in the management of refractory metastatic colorectal cancer in Australia

Price

Burge

Chantrill

et al. 2020

Asia-Pac J Clncl Oncology

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Trifluridine/tipiracil is available on the Australian Pharmaceutical Benefits Scheme for the treatment of patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, fluoropyrimidine-, oxaliplatin-and irinotecan-based chemotherapies, antivascular endothelial growth factor agents and anti-epidermal growth factor receptor agents. This article reviews trifluridine/tipiracil clinical data and presents practical information on its use in the management of refractory mCRC in Australia. Whereas the primary mechanism of action of fluoropyrimidines such as fluorouracil (5-FU) and capecitabine is enzyme inhibition of nucleotide synthesis, trifluridine/tipiracil primarily acts by incorporation into DNA, resulting in DNA dysfunction.Trifluridine/tipiracil has activity in patients with 5-FU-resistant tumors and can be considered in patients with prior intolerance or toxicity to 5-FU. In the pivotal phase III RECOURSE trial evaluating trifluridine/tipiracil in chemotherapy-refractory mCRC, efficacy benefits were observed across all a priori prognostic subgroups including those defined by age (≥65 and ≥75 years), geographical origin, primary tumor site or KRAS status. Trifluridine/tipiracil therapy benefits appropriately selected patients who have an ECOG performance status of 0 or 1, with no more than mild hepatic impairment or mild-to-moderate renal impairment, and who are capable of adhering to oral therapy safely. Appropriate dosing, monitoring for adverse events and effective management of side effects are essential.

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Trifluridine/Tipiracil and Regorafenib in Patients with Metastatic Colorectal Cancer: A Retrospective Study at a Tertiary Oncology Center

et al. 2021

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Background. Trifluridine/tipiracil (FTD/TPI) and regorafenib prolong survival for patients with refractory metastatic colorectal cancer (mCRC); limited comparative effectiveness data exist. Materials and Methods. A retrospective, longitudinal cohort study of patients with mCRC who initiated FTD/TPI or regorafenib (index therapy) between 2012-2017 at a US tertiary oncology center, Dana-Farber Cancer Institute, was conducted. Using best tumor response assessments, realworld 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 2nd-or 3rdline were performed. Results. 126 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 OR=2.6, all p-value<0.05; rwDCR 64.2% vs. 46.1%, adjusted OR=2.5, all p-value<0.05). Similar findings were observed for FTD/TPI versus regorafenib as 2nd-or 3rd-line therapy (rwORR 54.8% vs. 25.9%, adjusted OR=4.1, all p-value<0.05; rwDCR 69.0% vs. 37.0%, adjusted OR=4.9, all p-value<0.05). A greater proportion of patients treated with FTD/TPI versus regorafenib survived at 3 months (86.2% vs. 73.4%, p=0.016) and 4 months (79.6% vs. 65.8%, p=0.017). Adjusted OS hazard ratio for FTD/TPI versus regorafenib was 0.80, p=0.157. Conclusion.Patients treated with FTD/TPI had better tumor response and disease control than patients treated with regorafenib. Subgroup analysis in 2nd-or 3rd-line suggests that early use of FTD/TPI may have clinical benefits.Implications for Practice Statement: This real-world retrospective study compared clinical outcomes and clinical conditions between patients with refractory mCRC treated with FTD/TPI vs. regorafenib. Compared with patients treated with regorafenib, patients treated with FTD/TPI were significantly less likely to have dose modifications and more likely to have higher real-world objective response rate (rwORR) and real-world disease control rate (rwDCR) based on best tumor response while treated. Patients treated with FTD/TPI vs. regorafenib had significantly greater odds of having rwORR or rwDCR in adjusted analyses. Monthly survival rates were higher overall in patients treated with FTD/TPI vs. regorafenib in the first 6 months of follow-up, particularly at months 3 and 4. Adjusted overall survival results were similar between treatment groups. Clinical conditions while on treatment were consistent with the literature. This study offers insight into patients' treatment experience in real-world clinical settings. The Oncologist 2021;9999:• •

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Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study

Cited by 91 publications

References 20 publications

Review of metastatic colorectal cancer treatment pathways and early clinical experience of trifluridine/tipiracil in the UK named patient programme

Review of metastatic colorectal cancer treatment pathways and early clinical experience of trifluridine/tipiracil in the UK named patient programme

Trifluridine/tipiracil: A practical guide to its use in the management of refractory metastatic colorectal cancer in Australia

Trifluridine/Tipiracil and Regorafenib in Patients with Metastatic Colorectal Cancer: A Retrospective Study at a Tertiary Oncology Center

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