TAS-102 Safety in Metastatic Colorectal Cancer: Results From the First Postmarketing Surveillance Study

Abstract

Background: Unexpected toxicities of newly approved drugs might be revealed in clinical practice after market launch. This postmarketing surveillance study investigated expected and unexpected adverse drug reactions (ADRs) of TAS-102 in clinical practice in the first 6 months after market launch.

Patients and methods: All metastatic colorectal cancer (mCRC) patients (pts) received TAS-102 35 mg/m² as a starting dose orally twice daily for 5 consecutive days, with 2 days of rest per week for 2 weeks, followed by a 14-day rest period. ADRs during treatment courses were reported spontaneously by attending physicians.

Results: From May 26 to November 25, 2014, 3420 mCRC pts were treated with TAS-102 at 1134 institutes in Japan. In total, 370 ADRs (185 ADRs of myelosuppression and related infection in 125 pts, of which 58 ADRs in 31 pts were serious ADRs [SADRs] and 127 ADRs in 98 pts were non-SADRs) were observed in 219 pts and included 89 SADRs in 51 pts and 281 non-SADRs in 183 pts (a pt was counted twice if SADR and non-SADR were experienced). The most frequent ADRs were: myelosuppression comprising neutropenia (n = 77), leukopenia (n = 28), thrombocytopenia (n = 23), anemia (n = 20), and febrile neutropenia (FN; n = 19). Serious neutropenia and FN tended to occur from days 15 to 21 in the first cycle in 12 (75%) of 16 pts.

Conclusion: The ADRs and safety profile of TAS-102 in this study was similar to that in recent TAS-102 clinical trials, without unexpected safety signals. Careful monitoring should be undertaken in pts with serious neutropenia around day 15 in the first cycle of treatment to prevent FN.

Keywords: Adverse drug reaction; Clinical practice; Febrile neutropenia; Neutropenia; Real-world.