Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer

Daisuke Kotani, Yasutoshi Kuboki, Satoshi Horasawa, Asumi Kaneko, Yoshiaki Nakamura, Akihito Kawazoe, Hideaki Bando, Hiroya Taniguchi, Kohei Shitara, Takashi Kojima, Akihito Tsuji, Takayuki Yoshino, Daisuke Kotani, Yasutoshi Kuboki, Satoshi Horasawa, Asumi Kaneko, Yoshiaki Nakamura, Akihito Kawazoe, Hideaki Bando, Hiroya Taniguchi, Kohei Shitara, Takashi Kojima, Akihito Tsuji, Takayuki Yoshino

Abstract

Background: A previous phase I/II C-TASK FORCE study of trifluridine/tipiracil plus bevacizumab for patients with heavily pretreated metastatic colorectal cancer (mCRC) showed promising activity with an acceptable toxicity profile. This retrospective study aimed to investigate the safety and efficacy of trifluridine/tipiracil plus bevacizumab compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC in clinical settings.

Methods: Records of patients with mCRC refractory to standard therapies who initiated trifluridine/tipiracil plus bevacizumab from January 2016 to March 2018 or trifluridine/tipiracil monotherapy from June 2014 to December 2015 were retrospectively reviewed at our institution.

Results: Totally, 60 patients received trifluridine/tipiracil plus bevacizumab and 66 received trifluridine/tipiracil monotherapy. All patients had previously received standard chemotherapy. Median progression-free survival (PFS) was 3.7 months [95% confidence interval (CI), 2.3-5.1] in the trifluridine/tipiracil plus bevacizumab group and 2.2 months (95% CI, 1.8-2.6) in the trifluridine/tipiracil monotherapy group [hazards ratio (HR) 0.69; 95% CI 0.48-0.99]. PFS rate at 16 weeks was 46.6% for the trifluridine/tipiracil plus bevacizumab group and 33.9% for the trifluridine/tipiracil monotherapy group. Although a relatively higher incidence of grade ≥ 3 neutropenia was observed in the trifluridine/tipiracil plus bevacizumab group than that in the other group (50.0% vs. 40.9%, p = 0.371), the incidence of febrile neutropenia was not high (3.3% vs. 7.8%, p = 0.444).

Conclusions: In real-world settings, trifluridine/tipiracil plus bevacizumab prolonged PFS and helped achieve higher 16-week PFS rate compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC with manageable toxicities.

Trial registration: Retrospectively registered.

Keywords: Lonsurf; TAS-102; Trifluridine/tipiracil plus bevacizumab; mCRC.

Conflict of interest statement

DK reports receiving honoraria from Takeda, Chugai, Lilly, and Merck Serono. YK reports receiving honoraria from Taiho, research funding from Taiho, Takeda, Ono, AstraZeneca, INC research, Daiichi-Sankyo, and Boehringer Ingelheim. YN reports research funding from Ono and Taiho. AK2 reports receiving research funding from Ono, Sumitomo Dainippon and Taiho. HB reports receiving lecturer fee from Taiho and Lilly; research expenses from Taiho, AstraZeneca, and Sysmex. HT reports receiving honoraria from Takeda, Chugai, Merck Serono, Taiho, Bayer, Lilly, Yakult, and Sanofi. KS reports paid consulting or advisory roles for Astellas, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono and MSD; honoraria from Novartis, AbbVie, and Yakult; and research funding from Astellas, Lilly, Ono, Sumoitomo Dainippon, Daiichi Sankyo, Taiho, Chugai, MSD and Medi Science. TK reports receiving research funding from Shionogi, MSD, Ono Pharmaceutical, Chugai, Oncolys BioPharma, Astellas Amgen BioPharma, and Parexel. AT reports receiving honoraria from Daiichi-Sankyo, Taiho, Chugai, Merck Serono, Takeda, and Bristol-Myers Squibb; speaker’s bureau from Chugai, Taiho, Takeda, and Merck Serono. YK reports receiving honoraria Takeda, Chugai, Bristol-Myers Squibb, Ono, Merck Biopharma, Taiho, Bayer, Lilly, Yakult Honsha, Sanofi, Nipro, Moroo, Asahi Kasei, Mitsubishi Tanabe, Otsuka, Medical Review, and Shiseido; research funding from MSD, Daiichi Sankyo, NanoCarrier, Eisai, Sysmex, Shionogi, IQVIA, Parexel International, Astellas, Mediscience, Sumitomo Dainippon, A2 Healthcare, Ono, Taiho, Bayer, Yakult Honsha, and Sanofi. TS reports receiving honoraria from Chugai, Merck Serono, Bristol-Myers Squibb, Takeda, Yakult Honsha, Lilly, Bayer Yakuhin, Ono, Merck, Astellas Pharma, Taiho, and Nihonkayaku; consulting or advisory role from Bayer, Lilly, Ono, Takara Bio, Merck Serono, and Nihonkayaku; research funding from Yakult Honsha, Chugai, Ono, Sanofi, Lilly, Daiichi Sankyo, Merck Serono, Gilead Sciences, and Dainippon Sumitomo. TE reports receiving honoraria from Lilly, Taiho, Bristol-Myers Squibb Japan, Eisai, Daiichi Sankyo, Merck Serono, Chugai, Ono, Takeda, Bayer, and Sanofi; research funding from Daiichi Sankyo, Merck Serono, MSD, Novartis, Dainippon Sumitomo, Ono, Astellas Pharma, Lilly, Bayer, Nihonkayaku, Pfizer, and Bristol-Myers Squibb Japan. SN reports receiving honoraria from Taiho and Astrazeneca. AS reports receiving research funding from MSD, Eisai, Ono, Taiho, Takeda, and Bayer. AO reports receiving honoraria from Ono, BMS, Chugai, Taiho, Eisai, and Amgen; research funding from Bristol-Myers Squibb; immediate family member of Atsushi Ohtsu have been employed by Celgene. TY reports receiving research funding from Novartus, MSD, Sumitomo Dainippon, Chugai, Sanofi, Daiichi-Sankyo, Parexel, Ono, GlaxoSmithKline, and Boehringer Ingelheim.

Figures

Fig. 1
Fig. 1
a Kaplan–Meier plots for PFS. b Kaplan–Meier plots for OS

References

    1. International Agency for Research on Cancer: GLOBOCAN 2018. . Accessed 02 July 2019.
    1. Heinmann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–1075. doi: 10.1016/S1470-2045(14)70330-4.
    1. Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with kras wild-type advanced or metastatic colorectal cancer. JAMA. 2017;317:2392–2401. doi: 10.1001/jama.2017.7105.
    1. Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomized, double-blind, multicenter, phase 3 study. Lancet Oncol. 2015;16:499–508. doi: 10.1016/S1470-2045(15)70127-0.
    1. Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausová J, Macarulla T, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012;30:3499–3506. doi: 10.1200/JCO.2012.42.8201.
    1. Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicenter, randomized, placebo-controlled, phase 3 trial. Lancet. 2013;318:303–312. doi: 10.1016/S0140-6736(12)61900-X.
    1. Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372:1909–1919. doi: 10.1056/NEJMoa1414325.
    1. Yoshino T, Mizunuma N, Yamazaki K, Nishina T, Komatsu Y, Baba H, et al. TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomized, placebo-controlled phase 3 trial. Lancet Oncol. 2012;13:993–1001. doi: 10.1016/S1470-2045(12)70345-5.
    1. Xu J, Kim TW, Shen L, Sriuranpong V, Pan H, Xu R, et al. Results of a randomized, double-blind, placebo-controlled, phase III trial of trifluridine/tipiracil (TAS-102) monotherapy in Asian patients with previously treated metastatic colorectal cancer: the TERRA study. J Clin Oncol. 2017;36:350–358. doi: 10.1200/JCO.2017.74.3245.
    1. Tsukihara H, Nakagawa F, Sakamoto K, Ishida K, Tanaka N, Okabe H, et al. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, together with bevacizumab, cetuximab, or panitumumab on human colorectal cancer xenografts. Oncol Rep. 2015;33:2135–2142.
    1. Kuboki Y, Nishina T, Shinozaki E, Yamazaki K, Shitara K, Okamoto W, et al. TAS-102 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE): an investigator-initiated, open-label, single-arm, multicenter, phase 1/2 study. Lancet Oncol. 2017;18:1172–1181. doi: 10.1016/S1470-2045(17)30425-4.
    1. Lesniewski-Kmak K, Moiseenko V, Saunders M, Wasan H, Argiles G, Borg C, et al. Phase II study evaluating trifluridine/tipiracil + bevacizumab and capecitabine + bevacizumab in first-line unresectable metastatic colorectal cancer (mCRC) patients who are non-eligible for intensive therapy (TASCO1): results of the primary analysis. Ann Oncol. 2018;29:mdy149.021. doi: 10.1093/annonc/mdy149.021.
    1. Kotani D, Shitara K, Kawazoe A, Fukuoka S, Kuboki Y, Bando H, et al. Safety and efficacy of trifluridine/tipiracil monotherapy in clinical practice for patients with metastatic colorectal cancer: experience at a single institution. Clin Colorectal Cancer. 2016;15:e109–e115. doi: 10.1016/j.clcc.2015.11.005.
    1. Oki E, Makiyama A, Miyamoto Y, Kotaka M, Kawanaka H, Miwa K, et al. Trifluridine/tipiracil plus bevacizumab in elderly patients with previously untreated metastatic colorectal cancer (KSCC1602): A multicenter, phase II clinical trial. J Clin Oncol. 2019;37(suppl):abstr 3548. doi: 10.1200/JCO.2019.37.15_suppl.3548.
    1. Yoshino T, Oki E, Nozawa H, Eguchi-Nakajima T, Taniguchi H, Morita S, et al. Rationale and design of the TRUSTY study: a randomized, multicenter, open-label phase II/III study of trifluridine/tipiracil plus bevacizumab versus irinotecan, fluoropyrimidine plus bevacizumab as second-line treatment in patients with metastatic colorectal cancer progressive during following first-line oxaliplatin-based chemotherapy. ESMO Open. 2018;3:e000411. doi: 10.1136/esmoopen-2018-000411.
    1. Pfeiffer P, Yilmaz M, Möller S, Maltha L, Krogh M, Zitnjak D, et al. Randomized study evaluating trifluridine/tipiracil (TAS-102) versus + trifluridine/tipiracil + bevacizumab as last-line therapy in patients with chemorefractory unresectable metastatic colorectal cancer (mCRC) J Clin Oncol. 2019;37:637. doi: 10.1200/JCO.2019.37.4_suppl.637.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere