TABLE 2.
Efficacy in RET Fusion-Positive TC and RET-Mutant MTC
| Response | RET Fusion-Positive TC | RET-Mutant MTC | ||
|---|---|---|---|---|
| Treatment Naïve (n = 24)a | Previously Treated (n = 41) | Cabozantinib/Vandetanib Naïve (n = 143)b | Previously Treated (n = 152) | |
| Objective response rate by IRC,c % (95% CI) | 95.8 (78.9 to 99.9) | 85.4 (70.8 to 94.4) | 82.5 (75.3 to 88.4) | 77.6 (70.2 to 84.0) |
| Best overall response | ||||
| CR, No. (%) | 5 (20.8) | 5 (12.2) | 34 (23.8) | 19 (12.5) |
| PR, No. (%) | 18 (75.0) | 30 (73.2) | 84 (58.7) | 99 (65.1) |
| SD, No. (%) | 1 (4.2) | 6 (14.6) | 20 (14.0) | 25 (16.4) |
| PD, No. (%) | 0 | 0 | 2 (1.4) | 2 (1.3) |
| Not evaluable | 0 | 0 | 3 (2.1) | 7 (4.6) |
| Clinical benefit rate,d,e % (95% CI) | 100 (85.8 to 100) | 100 (91.4 to 100) | 94.4 (89.3 to 97.6) | 91.4 (85.8 to 95.4) |
| DoR | ||||
| Median (95% CI)f,g months | NE (42.8 to NE) | 26.7 (12.1 to NE) | NE (51.3 to NE) | 45.3 (33.6 to NE) |
| Patients with censored data, No. (%) | 21 (91.3) | 20 (57.1) | 87 (73.7) | 72 (61.0) |
| Rate of DoR at median follow-up time, % (95% CI) | 100 (100 to 100) | 45.6 (25.6 to 63.6) | 72.4 (62.2 to 80.3) | 55.7 (44.8 to 65.3) |
| Rate of DoR,g,h % (95% CI) | ||||
| 1 year | 100 (NE to NE) | 71.7 (52.4 to 84.2) | 91.4 (84.6 to 95.3) | 83.0 (74.6 to 88.8) |
| 2 years | 90.9 (50.8 to 98.7) | 50.7 (30.4 to 67.8) | 84.1 (75.9 to 89.7) | 66.4 (56.3 to 74.7) |
| 3 years | 90.9 (50.8 to 98.7) | 45.6 (25.6 to 63.6) | 76.7 (67.4 to 83.7) | 60.3 (49.8 to 69.3) |
| 4 years | NE (NE to NE) | 45.6 (25.6 to 63.6) | 67.6 (55.6 to 77.0) | 48.5 (36.2 to 59.7) |
| 5 years | — | — | NE (NE to NE) | 48.5 (36.2 to 59.7) |
| PFS | ||||
| Disease progression, No. (%) | 3 (12.5) | 16 (39.0) | 33 (23.1) | 53 (34.9) |
| Median (95% CI)f,g months | NE (44.2 to NE) | 27.4 (14.5 to NE) | NE (53.1 to NE) | 41.4 (30.2 to NE) |
| Patients with censored data, No. (%) | 21 (87.5) | 24 (58.5) | 104 (72.7) | 83 (54.6) |
| Rate of PFS at median follow-up time, % (95% CI) | 87.3 (56.4 to 96.8) | 49.5 (31.1 to 65.4) | 70.2 (60.9 to 77.8) | 47.8 (38.50 to 56.6) |
| Rate of PFS,g,h % (95% CI) | ||||
| 1 year | 95.2 (70.7 to 99.3) | 70.6 (53.2 to 82.6) | 91.1 (84.8 to 94.8) | 79.5 (71.8 to 85.3) |
| 2 years | 95.2 (70.7 to 99.3) | 57.1 (38.6 to 71.8) | 82.5 (74.8 to 88.0) | 64.9 (56.2 to 72.3) |
| 3 years | 87.3 (56.4 to 96.8) | 49.5 (31.1 to 65.4) | 75.2 (66.8 to 81.8) | 54.6 (45.6 to 62.8) |
| 4 years | 65.5 (17.5 to 90.2) | 49.5 (31.1 to 65.4) | 65.9 (55.1 to 74.8) | 45.9 (36.2 to 55.1) |
| 5 years | NE (NE to NE) | 49.5 (31.1 to 65.4) | NE (NE to NE) | 41.6 (31.1 to 51.7) |
| OS | ||||
| Median (95% CI)f,g months | NE (NE to NE) | NE (25.3 to NE) | NE (NE to NE) | 64.3 (48.3 to NE) |
| Patients with censored data, No. (%) | 23 (95.8) | 30 (73.2) | 128 (89.5) | 96 (63.2) |
| Rate of OS at median follow-up time, % (95% CI) | 94.4 (66.6 to 99.2) | 65.5 (46.0 to 79.4) | 88.8 (82.0 to 93.1) | 63.4 (54.7 to 70.9) |
| Rate of OS,g,h % (95% CI) | ||||
| 1 year | 100 (NE to NE) | 94.8 (80.7 to 98.7) | 99.3 (95.0 to 99.9) | 87.8 (81.3 to 92.1) |
| 2 years | 94.4 (66.6 to 99.2) | 76.4 (58.1 to 87.5) | 94.9 (89.7 to 97.5) | 76.6 (68.8 to 82.7) |
| 3 years | 94.4 (66.6 to 99.2) | 65.5 (46.0 to 79.4) | 89.7 (83.3 to 93.8) | 67.8 (59.4 to 74.8) |
| 4 years | 94.4 (66.6 to 99.2) | 65.5 (46.0 to 79.4) | 88.8 (82.0 to 93.1) | 60.7 (51.5 to 68.7) |
| 5 years | NE (NE to NE) | 65.5 (46.0 to 79.4) | 88.8 (82.0 to 93.1) | 57.1 (47.1 to 65.9) |
Abbreviations: CR, complete response; DoR, duration of response; IRC, independent review committee; MTC, medullary thyroid cancer; NE, not evaluable; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; RET, REarranged during Transfection; SD, stable disease; TC, thyroid cancer.
Treatment naïve refers to therapies other than radioactive iodine.
Cabozantinib/vandetanib naïve included treatment-naïve patients (n = 116) and patients who were not previously treated with cabozantinib/vandetanib (n = 27).
Objective response rate was defined as the proportion of patients with a best overall response of confirmed CR or PR.
95% CI was calculated using the Clopper-Pearson method.
Clinical benefit rate (%) was defined as the proportion of patients with a best overall response of a confirmed CR, PR, or SD lasting ≥16 weeks. SD was measured from the date of the first dose of selpercatinib until the criteria for PD were first met.
95% CIs were calculated using the Brookmeyer-Crowley method.
Estimate based on the Kaplan-Meier method.
95% CIs were calculated using the Greenwood formula.