Phase Ib/II Study of Biweekly TAS-102 in Combination with Bevacizumab for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies (BiTS Study)

Satake, Hironaga; Kato, Takeshi; Oba, Koji; Kotaka, Masahito; Kagawa, Yutaka; Yasui, Hisateru; Nakamura, Masato; Watanabe, Takanori; Matsumoto, Toshihiko; Kii, Takayuki; Terazawa, Tetsuji; Makiyama, Akitaka; Takano, Nao; Yokota, Mitsuru; Okita, Yoshihiro; Matoba, Koreatsu; Hasegawa, Hiroko; Tsuji, Akihito; Yoshino, Takayuki; Yamazaki, Kentaro; Mishima, Hideyuki; Oki, Eiji; Nagata, Naoki; Sakamoto, Junichi

doi:10.1634/theoncologist.2020-0643

Cited by 38 publications

(22 citation statements)

References 16 publications

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“…In the future, further refinements to the FTD/TPI plus bevacizumab regimen may improve its safety and/or tolerability without compromising efficacy. Recently, a simplified regimen, in which FTD/TPI was administered every 2 weeks instead of in weeks 1 and 2 of each 4-week cycle, has been found to produce less grade ≥3 neutropenia than the 'standard' FTD/TPI plus bevacizumab regimen used in the C-TASK FORCE and Danish trials (15.9 vs 72 and 67%, respectively) [20,21], but with comparable median OS (10.9 vs 11.4 and 9.4 months, respectively) [31]. Although these results are preliminary, a simplified regimen could maintain outcomes with FTD/TPI plus bevacizumab while reducing hematologic toxicity, antibiotic use and the need for hematopoietic support.…”

Section: Discussion and Future Perspectivementioning

confidence: 99%

Trifluridine/Tipiracil Plus Bevacizumab for Third-Line Management of Metastatic Colorectal Cancer: SUNLIGHT Study Design

Tabernero¹,

Taı̈eb

Prager

et al. 2021

Future Oncol.

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Trifluridine/tipiracil (FTD/TPI) is an orally active formulation of trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor that increases the bioavailability of trifluridine. Preliminary studies of FTD/TPI plus bevacizumab have produced encouraging results in the treatment of refractory metastatic colorectal cancer. Here, we describe the design of the multinational Phase III SUNLIGHT, an open-label study of FTD/TPI plus bevacizumab as third-line treatment for patients with unresectable metastatic colorectal cancer. A total of 490 patients will be randomized 1:1 to receive either FTD/TPI plus bevacizumab, or FTD/TPI monotherapy. The primary objective is to significantly improve overall survival with FTD/TPI plus bevacizumab compared with FTD/TPI monotherapy. The first patient was enrolled in November 2020.

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Section: Discussion and Future Perspectivementioning

confidence: 99%

Trifluridine/Tipiracil Plus Bevacizumab for Third-Line Management of Metastatic Colorectal Cancer: SUNLIGHT Study Design

Tabernero¹,

Taı̈eb

Prager

et al. 2021

Future Oncol.

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“…In addition, FTD/TPI plus bevacizumab (Bev) is an alternative treatment option as a third-or later-line chemotherapy for patients with mCRC, as this treatment is safe and leads to a higher disease control rate (DCR) and longer progression-free survival (PFS) and overall survival (OS), than FTD/TPI monotherapy. Nevertheless, there are only a few phase I/II (11)(12)(13) or randomized phase II trials (14) investigating the efficacy of FTD/TPI + Bev. Moreover, because the PFS following this salvage-line treatment is still low, predictors of early treatment efficacy are important to help optimize treatment strategies; however, the efficacy predictors of FTD/TPI + Bev remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Effect of neutropenia on survival outcomes of patients with metastatic colorectal cancer receiving trifluridine/tipiracil plus bevacizumab

et al. 2021

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Trifluridine (FTD)/tipiracil (TPI) plus bevacizumab (Bev) is a promising late-line treatment in metastatic colorectal cancer (mCRC). Although chemotherapy-induced neutropenia (CIN) is a well-known predictor of FTD/TPI efficacy, whether CIN is a predictive marker of efficacy for FTD/TPI + Bev remains unclear. Thus, the present study aimed to investigate the clinical outcomes of FTD/TPI + Bev and the predictive markers of its efficacy. Clinical data of patients with mCRC who received FTD/TPI + Bev at the Cancer Institute Hospital between January 2017 and August 2020 were retrospectively collected. Disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety were assessed. In addition, subgroup analyses of prognostic and predictive efficacy markers were performed. In total, 94 patients (median age, 60.0 years; age range, 32–82 years; 37 men and 57 women) were included in the present study. The DCR was 44.7%, the median PFS time was 2.9 months (2.3–4.1 months) and the median OS time was 10.0 months (7.3–11.1 months). Grade 3 or 4 CIN within the first cycle of treatment occurred in 27.7% of patients, which was significantly associated with a longer PFS time than those who did not develop CIN [3.8 months (2.3–8.4 months) vs. 2.7 months (1.8–4.0 months); P=0.008]. Furthermore, the DCR was higher in patients with grade 3 or 4 CIN within the first cycle of treatment than those without CIN (61.5 vs. 38.2%; P=0.07). Multivariate Cox regression analysis revealed that grade 3 or 4 CIN within the first cycle of treatment are independent predictors for a longer PFS time (P=0.01). Taken together, the results of the present study suggest that grade 3 or 4 CIN within the first cycle of treatment are early predictors of the efficacy of FTD/TPI + Bev.

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“…It is also possible that even if patients had Grade ≥ 3 CIN and could have continued panitumumab monotherapy while suspending FTD/TPI due to Grade ≥ 3 CIN, investigators may have decided to simply suspend both treatments; this would account for the low panitumumab RDI. Recently, it was reported that in heavily pre-treated patients (refractory to chemotherapy, anti-VEGF, and anti-EGFR therapy [for tumours with wild-type RAS]) biweekly administration of FTD/TPI with bevacizumab showed promising anti-tumour activity with acceptable toxicity and dramatically decreased CIN compared with the standard combination treatment schedule [20]. Thus, if panitumumab was combined with biweekly FTD/TPI, it may be possible to decrease CIN and maintain the RDI of both drugs, although additional studies are required to explore this possibility.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

et al. 2021

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Background We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

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Phase Ib/II Study of Biweekly TAS-102 in Combination with Bevacizumab for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies (BiTS Study)

Cited by 38 publications

References 16 publications

Trifluridine/Tipiracil Plus Bevacizumab for Third-Line Management of Metastatic Colorectal Cancer: SUNLIGHT Study Design

Trifluridine/Tipiracil Plus Bevacizumab for Third-Line Management of Metastatic Colorectal Cancer: SUNLIGHT Study Design

Effect of neutropenia on survival outcomes of patients with metastatic colorectal cancer receiving trifluridine/tipiracil plus bevacizumab

Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

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