Table 9.
Summary of clinical outcomes of second-line key trials
| RESORCE844 |
CELESTIAL845 |
REACH-2847 |
CheckMate-040853 |
CheckMate-040855 |
KEYNOTE-394846 |
|||||
|---|---|---|---|---|---|---|---|---|---|---|
| REG | PBO | CAB | PBO | RAM | PBO | NIV | NIV+IPI | PEM | PBO | |
| Number of patients allocated | 379 | 194 | 470 | 237 | 197 | 95 | 214* | 50† | 300 | 153 |
| Median OS (months) | 10.6 | 7.8 | 10.2 | 8.0 | 8.5 | 7.3 | 9-month 74% | 22.8 | 14.6 | 13.0 |
| HR (95% CI) | 0.63 (0.50–0.79); P<0.0001 | 0.76 (0.63–0.92); P=0.005 | 0.710 (0.531–0.949); P=0.0199 | NA | NA | 0.79 (0.63–0.99); P=0.0180 | ||||
| Median PFS (months) | 3.1 | 1.5 | 5.2 | 1.9 | 2.8 | 1.6 | 4.0 | NA | 2.6 | 2.3 |
| HR (95% CI) | 0.44 (0.37–0.56); P<0.0001 | 0.44 (0.36–0.52); P<0.001 | 0.452 (0.339–0.603); P<0.0001 | NA | NA | 0.74 (0.60–0.92); P=0.0032 | ||||
| Median TTP (months) | 3.2 | 1.5 | NA | NA | 3.0 | 1.6 | 4.1 | NA | 3.8 | 2.8 |
| HR (95% CI) | 0.44 (0.36–0.55); P<0.0001 | NA | 0.427 (0.313–0.582); P<0.0001 | NA | NA | 0.69 (0.54–0.88); P=0.0011 | ||||
| ORR/CR (%) | 11.0/1.0 | 4.0/0.0 | 4.0/0.0 | <1.0/0.0 | 5.0/0.0 | 1.0/0.0 | 20.0/1.0 | 32.0/8.0 | 12.7/2.0 | 1.3/0.7 |
| DCR (%) | 65.0 | 36.0 | 64.0 | 33.0 | 59.9 | 38.9 | 64.0 | 54.0 | 51.0 | 47.1 |
| Median duration of treatment (months) | 3.6 | 1.9 | 3.8 | 2.0 | 12 weeks | 8 weeks | NA | 5.1 | NA | NA |
| Median duration of response (months) | NA | NA | NA | NA | NA | NA | 9.9 | 17.5 | 23.9 | 5.6 |
| Response evaluation | mRECIST | RECIST v1.1 | RECIST v1.1 | RECIST v1.1 | RECIST v1.1 | RECIST v1.1 | ||||
REG, regorafenib; PBO, placebo; CAB, cabozantinib; RAM, ramucirumab; NIV, nivolumab; IPI, ipilimumab; PEM, pembrolizumab; OS, overall survival; HR, hazard ratio; CI, confidence interval; NA, not available; PFS, progression-free survival; TTP, time-to-progression; ORR, objective response rate; CR, complete response; DCR, disease control rate; mRECIST, modified Response Evaluation Criteria in Solid Tumors; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1.
*
214 patients in the dose expansion phase.
†
Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (4 doses) followed by nivolumab 240 mg intravenously every 2 weeks.