3053 - JFMC51-1702-C7: Phase II study investigating efficacy and safety of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients (pts) with metastatic colorectal cancer (mCRC) refractory or intolerant to standard chemotherapies.

Background

Combination treatment of FTD/TPI plus BEV in the C-TASK FORCE showed a promising activity in pts with mCRC refractory or intolerant to standard chemotherapies; however, due to the small sample size, it remains unclear if this combination works in the same way; RAS wild-type or mutant. We investigated the efficacy and safety of this combination in separate cohorts of RAS wild-type and mutant.

Methods

mCRC pts refractory or intolerant to prior treatments with fluoropyrimidines, irinotecan, oxaliplatin, an angiogenesis inhibitor, and an anti-EGFR antibody if RAS wild-type, and without FTD/TPI and regorafenib. Pts received FTD/TPI (35 mg/m², twice daily, days 1 to 5 and 8 to 12) and BEV (5mg/kg, day1 and 15) every four weeks. The primary endpoint was disease control rate (DCR). A threshold and expected value of the DCR in each wild-type and mutant were set as 44% and 65%, respectively. Assuming a one-sided significance level of 5.0%, each target sample size was estimated to be 49 to achieve a power of 90%.

Results

From Jan to Sep 2018, 102 pts were enrolled, and 98 pts fulfilled the eligibility (49 pts in each). Baseline characteristics of RAS wild-type vs. mutant were follows; median age, 65 vs. 64 years: male, 51% vs. 59%: ECOG PS 0, 69% vs. 59%: left-sided primary, 84% vs. 67%: number of metastasis of > 2, 71% vs. 74%: median time from diagnosis of metastasis, 32.9 vs 21.2 months. The DCR in RAS wild-type was 65.3% (90% CI: 52.6-76.5%, p = 0.0022), while that in RAS mutant was 55.1% (90% CI: 42.4-67.3%, p = 0.0780). There was not a statistically significant difference in DCR between RAS wild-type and mutant after adjustment of baseline characteristics (adjusted odds ratio=0.48, 90% CI: 0.21-1.10, p = 0.1435). Partial response was observed only in three pts with RAS wild-type. There were neither unexpected safety signals nor treatment related death.

Conclusions

FTD/TPI plus BEV showed a promising activity with an acceptable safety profile for previously treated mCRC harboring either RAS wild-type or mutant. Survival outcome will be presented at the meeting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Japanese Fondation for Multidisciplinary Treatment of Cancer (JFMC).

Funding

Japanese Fondation for Multidisciplinary Treatment of Cancer (JFMC).

Disclosure

M. Nakamura: Honoraria (self): Taiho Yakuhin; Honoraria (self): Daiichi Sankyo; Honoraria (self): Chugai Seiyaku; Honoraria (self): Merck. A. Makiyama: Advisory / Consultancy: Eli Lily Pharm; Speaker Bureau / Expert testimony: Chugai Pharm; Speaker Bureau / Expert testimony: Eli Lily Pharm; Speaker Bureau / Expert testimony: Taiho Pharm; Speaker Bureau / Expert testimony: Takeda Pharm. K. Oba: Honoraria (self): Chugai Pharm; Honoraria (self): Novartis Pharm; Honoraria (self): Takeda Pharm; Honoraria (self): BMS; Honoraria (self): Pfizer; Honoraria (self): Tsumura Pharm. T. Yoshino: Research grant / Funding (self): Novartis Pharma; Research grant / Funding (self): MSD; Research grant / Funding (self): Sumitomo Dainippon Pharma; Research grant / Funding (self): Chugai Pharmaceutical; Research grant / Funding (self): Sanofi; Research grant / Funding (self): Daiichi Sankyo Company; Research grant / Funding (self): Parexel; Research grant / Funding (self): Ono Pharmaceutical. K. Yoshida: Research grant / Funding (self): Chugai Pharma; Research grant / Funding (self): Lilly; Research grant / Funding (self): MSD; Research grant / Funding (self): Ono Pharma; Honoraria (self): EA Pharma; Honoraria (self): Johnson & Johnson; Honoraria (self): SBI Pharma; Honoraria (self): Olympus; Honoraria (self): Covidien; Honoraria (self): Sanofi; Honoraria (self): TERUMO; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Tsumura; Honoraria (self): Asahi Kasei; Honoraria (self): Pharma International Osaka; Honoraria (self): Daiichi Sankyo; Honoraria (self): Chugai; Honoraria (self): Lilly; Honoraria (self): Takeda; Honoraria (self): Yakult Honsha. K. Yamazaki: Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Chugai. E. Oki: Speaker Bureau / Expert testimony: Taiho Pharm; Speaker Bureau / Expert testimony: Chugai Pharm. T. Takahashi: Speaker Bureau / Expert testimony: Taiho Pharm; Speaker Bureau / Expert testimony: Chugai Pharm. All other authors have declared no conflicts of interest.