First-line trifluridine/tipiracil plus bevacizumab for unresectable metastatic colorectal cancer: SOLSTICE study design

Thewis, André; Saunders, Mark; Kanehisa, Akira; Gandossi, E.; Fougeray, Ronan; Amellal, Nadia; Falcone, Alfredo

doi:10.2217/fon-2019-0786

Cited by 21 publications

(17 citation statements)

References 32 publications

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“…Two randomized Phase II studies have been conducted worldwide, in which better survival was shown compared to FTD/TPI monotherapy or capecitabine +Bev 16,17 . As a result, two randomized Phase III studies for first‐line and second‐line treatments are currently being conducted 18,19 …”

Section: Introductionmentioning

confidence: 99%

Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

et al. 2020

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Background A previous Phase I/II study demonstrated that TAS‐102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. Methods This is a multicenter, single‐arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression‐free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs). Results Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70–88); the ECOG‐PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3–4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%). Conclusions FTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross‐resistance with 5‐fluorouracil. Clinical trial registration: UMIN clinical trials registry (UMIN000025241).

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Section: Introductionmentioning

confidence: 99%

Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

et al. 2020

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“…Decisions regarding subsequent systemic therapy for mCRC, following disease progression beyond second-line treatments, primarily depend on the agents that were previously used. 24 - 26 TAS-102 is an antimetabolic agent that can prolong the OS of heavily treated patients with mCRC by 2 months. 18 On the other hand, regorafenib and fruquintinib are small molecule inhibitors that block multiple kinases, including VEGFR, FGFR , and PDGFR , among others.…”

Section: Discussionmentioning

confidence: 99%

Systematic Review and Meta-Analysis of Multitargeted Tyrosine Kinase Inhibitors in Patients With Intractable Metastatic Colorectal Cancer

Gao

Cao

Bao

et al. 2020

Technol Cancer Res Treat

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Background: The treatment options for intractable metastatic colorectal cancer include regorafenib, trifluridine/tipiracil, and fruquintinib. In this study, we aimed to conduct a network meta-analysis for comparing the efficacy of these agents. Methods: We searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials databases for relevant literature, up to February 2020. The data were collected from randomized controlled trials on regorafenib, trifluridine/tipiracil, or fruquintinib, administered to patients with metastatic colorectal cancer who failed on treatment with oxaliplatin, irinotecan, or fluoropyrimidine. The primary end points, namely, the overall survival and progression-free survival, were analyzed for subsequent network analysis using the Review Manager and Aggregate Data Drug Information System software for performing direct and indirect comparisons. Results: A total of 7 trials were analyzed in this study. Trifluridine/tipiracil and regorafenib proved to be superior to the placebo, with respect to the overall survival (odds ratio: 0.38, 95% confidence interval: 0.27-0.52 for trifluridine/tipiracil; odds ratio: 0.47, 95% confidence interval: 0.26-0.84 for regorafenib) and progression-free survival (odds ratio: 0.18, 95% confidence interval: 0.05-0.67 for trifluridine/tipiracil; odds ratio: 0.06, 95% confidence interval: 0.04-0.09 for regorafenib). Regorafenib (80 mg) was superior to the placebo in terms of the overall survival and progression-free survival and inferior to trifluridine/tipiracil and fruquintinib. Network analysis revealed that the efficacy of trifluridine/tipiracil and fruquintinib was fundamentally similar, and both the agents were superior to regorafenib. Conclusion: Regorafenib (80 mg) was superior to the placebo, but inferior to 160 mg regorafenib, trifluridine/tipiracil, and fruquintinib. This study further revealed that the efficiency of trifluridine/tipiracil and fruquintinib is identical, but their toxicity profiles are different.

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“…Whether this is drug specific, a consequence of acquired multiresistance to anticancer drugs, or merely reflects the natural course of the disease, remains to be elucidated. Of considerable relevance for this matter, the ongoing SOLSTICE phase III trial is now comparing TAS-102 plus bevacizumab versus capecitabine plus bevacizumab as first line treatment for patients not suitable for intensive therapy (12).…”

Section: Discussionmentioning

confidence: 99%

Real world aspects of palliative trifluridine plus tiperacil (TAS-102) in refractory metastatic colorectal cancer

Wallander¹,

Rolander²,

Åvall‐Lundqvist³

et al. 2020

J Gastrointest Oncol

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Background: While recent randomised phase III trials show that trifluridine/tiperacil (TAS-102) may prolong life in patients with refractory metastatic colorectal cancer (rmCRC), palliative aspects on its efficacy and tolerability in real world patients need further elucidation. Methods: A retrospective observational multicentre study was designed, including all patients with rmCRC who received TAS-102 under 2016-2019 in the South East Health Care region of Sweden. 48 patients were identified. Primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), time to ECOG performance status deterioration (PSD), safety and dose reductions, admission to and duration of access to palliative care, and administration of TAS-102 in the last 30 days before death. Results: Median OS, PFS, and time to PSD (a proxy for impaired quality of life) from start of TAS-102 were 6.4 months (95% CI: 4.4-8.4), 2.3 months (95% CI: 1.8-2.7) and 2.5 months (95% CI: 1.9-3.2), respectively. Following uni-and multivariable regression analyses, the number of previous treatment lines (≤2 vs. ≥3) was statistically independent for OS (median 7.8 vs. 5.3 months, P=0.05), PFS (median 2.4 vs. 1.8 months, P=0.03), and time to PSD (median 2.8 vs. 1.8 months, P=0.03). Thirty-four (71%) of the patients received reduced doses. The most common grade 3-4 toxicity was neutropenia (39%). Forty-three (90%) were admitted to GP or hospital-based home palliative care. Median time for access to any form of palliative care before death was 2.3 (95% CI: 0.5-3.2) months. Few patients (n=3, 7%) received their last dose of TAS-102 in their last 30 days of life. Conclusions: The outcome and tolerability of TAS-102 in rmCRC appear similar in a real-world context and randomised trials. The retrospective design and limited sample size preclude firm conclusions on subgroup analyses, but it appears that the prognosis is slightly better the earlier TAS-102 is introduced. Treatment durations are generally short, and early admission to a palliative care provider is recommended.

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First-line trifluridine/tipiracil plus bevacizumab for unresectable metastatic colorectal cancer: SOLSTICE study design

Cited by 21 publications

References 32 publications

Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

Systematic Review and Meta-Analysis of Multitargeted Tyrosine Kinase Inhibitors in Patients With Intractable Metastatic Colorectal Cancer

Real world aspects of palliative trifluridine plus tiperacil (TAS-102) in refractory metastatic colorectal cancer

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