Table 1.
Completed TAS-102 trials in mCRC
| First author (year) | Ph | Patient population | Treatment | Primary endpoint |
|---|---|---|---|---|
| Hong (2006)39 | I | 14, refractory mCRC | Dose de-escalation, daily D1–14 q 21 days | RP2D =50 mg/m2/day |
| Overman (2008)40 | I | 63, 52 with refractory mCRC | Dose escalation, daily D1–5 and D8–12 q 28 days (A) or D1–5 q 21 days (B) | RP2D =100 mg/m2/day (A) or 160 mg/m2/day (B) |
| Overman (2008)42 | I | 15, advanced solid tumors | Dose escalation, TID on D1–5 and D8–12 q 28 days | MTD =80 mg/m2/day divided into 3 doses daily |
| Doi (2012)41 | I | 21, 18 with refractory mCRC (Japan only) | Dose escalation, BID D1–5 and D8–12 q 28 days | RP2D =70 mg/m2/day divided into 2 doses daily |
| Yoshino (2012)44 | II | 169, refractory mCRC (Japan only) | 35 mg/m2 BID D1–5 and D8–12 q 28 days + BSC vs PBO + BSC (2:1) | OS =9.0 vs 6.6 months HR 0.56, 95% CI 0.39–0.81, P=0.0011 |
| Bendell (2015)43 | I | 27, refractory mCRC | Dose escalation, BID D1–5 and D8–12 q 28 days | RP2D =70 mg/m2/day divided into 2 doses daily |
| Mayer (2015)45 | III | 800, refractory mCRC | 35 mg/m2 BID D1–5 and D8–12 q 28 days + BSC vs PBO + BSC (2:1) | OS =7.1 vs 5.3 months, HR 0.68, 95% CI 0.58–0.81, P<0.001 |
| Doi (2015)68 | I | 10, refractory mCRC | Dose escalation, BID D1–5 and D8–12 + irinotecan D1 and D15 fixed 150 mg/m2 q 28 days | RP2Ds =50 mg/m2/day (TAS-102) divided into 2 doses daily, 150 mg/m2 (irinotecan) |
| Kuboki (2015)64 | I/II | 25, refractory mCRC | Dose de-escalation, BID D1–5 and D8–12 + bevacizumab D1 and D15 q 28 days | RP2Ds =70 mg/m2/day TAS-102, divided into 2 doses daily, 5 mg/kg bevacizumab. PFS @ 16 weeks =42.9%, 80% CI 27.8–59.0% |
Abbreviations: Ph, phase; mCRC, metastatic colorectal cancer; RP2D, recommended Phase II dose; D, day; TID, three times daily; MTD, maximum tolerated dose; BID, twice daily; BSC, best supportive care; PBO, placebo; OS, overall survival; HR, hazard ratio; CI, confidence interval; PFS, progression-free survival.