Table 3.
Efficacy outcomes in the selpercatinib (LIBRETTO-001) versus SoC (EC, RWD) 1L and ≥2L cohorts of patients with RET-mutation-positive a/mMTC, before and after PSM
| Treatment naïve cohort (1L) |
Pretreated cohort (≥2L) |
|||||||
|---|---|---|---|---|---|---|---|---|
| Before PSM (unadjusted) |
After PSM |
Before PSM (unadjusted) |
After PSM |
|||||
| Selpercatinib arm (N = 116) | SoC (N = 107) | Selpercatinib arm (N = 84) | SoC (N = 84) | Selpercatinib arm (N = 179) | SoC (N = 51) | Selpercatinib arm (N = 38) | SoC(N = 38) | |
| INV-assessed PFS (months) | ||||||||
| Median (95% CI) | NR (50.7-NR) | 24.0 (15.8-35.6) | NR (50.7-NR) | 26.1 (18.7-38.7) | 35.6 (27.6-44.3) | 11.6 (4.1-16.3) | 27.4 (18.3-44.3) | 11.6 (5.4-80.8) |
| HR (95% CI) | 0.34 (0.22-0.54) | 0.34 (0.20-0.58) | 0.43 (0.24-0.77) | 0.59 (0.31-1.14) | ||||
| P value | <0.0001 | <0.0001 | 0.005 | 0.116 | ||||
| Probability (%) of PFS (95% CI) | ||||||||
| 3 years | 77.9 (68.7-84.8) | 38.9 (28.7-49.0) | 77.9 (66.9-85.7) | 41.7 (29.8-53.1) | 49.8 (41.9-57.3) | 25.4 (11.8-41.5) | 41.1 (25.3-56.2) | 39.7 (22.4-56.6) |
| 5 years | 61.3 (45.3-73.9) | 26.7 (17.6-36.7) | 59.0 (41.0-73.2) | 31.0 (20.0-42.6) | 30.5 (21.9-39.5) | 25.4 (11.8-41.5) | 26.0 (12.1-42.3) | 39.7 (22.4-56.6) |
| Follow-up durationa (months) | ||||||||
| Median (95% CI) | 41.7 (39.1-44.8) | 82.1 (55.4-114.1) | 45.5 (41.6-47.2) | 82.1 (52.5-114.1) | 47.0 (44.0-49.7) | 16.1 (12.0-34.6) | 49.7 (39.5-55.2) | 14.8 (10.6-26.7) |
| OS | ||||||||
| Median (95% CI) | NR (NR-NR) | 105.8 (82.1-172.1) | NR (NR-NR) | 105.8 (82.1-172.1) | 64.3 (64.3-NR) | 63.7 (42.1-NR) | 64.3 (33.3-NR) | 63.7 (36.3-NR) |
| HR (95% CI) | 0.46 (0.23-0.91) | 0.41 (0.18-0.93) | 1.33 (0.69-2.57) | 1.25 (0.58-2.68) | ||||
| P value | 0.026 | 0.033 | 0.400 | 0.564 | ||||
| Estimate of OS (%), (95% CI) | ||||||||
| 3 years | 89.9 (82.5-94.3) | 83.9 (74.7-90.0) | 91.4 (82.8-95.8) | 83.7 (73.0-90.4) | 71.1 (63.6-77.3) | 71.2 (55.3-82.2) | 63.0 (45.7-76.2) | 71.8 (52.4-84.4) |
| 5 years | 88.7 (80.9-93.4) | 68.5 (57.4-77.3) | 89.9 (80.8-94.8) | 70.8 (58.3-80.2) | 61.9 (52.9-69.8) | 55.5 (36.6-70.8) | 57.6 (40.3-71.5) | 56.0 (34.0-73.2) |
| Follow-up durationa (months) | ||||||||
| Median (95% CI) | 44.5 (42.6-46.3) | 71.1 (58.6-83.3) | 46.0 (44.5-47.9) | 70.9 (55.4-83.3) | 46.6 (44.8-49.1) | 45.5 (34.6-64.9) | 46.6 (41.9-50.8) | 45.5 (31.0-64.9) |
| ORR | 84.5 | 26.2 | 85.7 | 28.6 | 73.7 | 21.6 | 76.3 | 26.3 |
| OR (95% CI) | 17.4 (8.5-35.7) | 17.6 (7.8-39.7) | 15.8 (6.3-39.7) | 24.5 (NR-NR)b | ||||
| P value | <0.0001 | <0.0001 | <0.0001 | NR | ||||
| DCR | 97.4 | 77.6 | 96.4 | 77.4 | 93.9 | 62.7 | 94.7 | 60.5 |
| OR (95% CI) | 9.9 (2.6-37.4) | 8.1 (2.2-29.2) | 42.2 (9.6-185.7) | 151.8 (NR-NR)b | ||||
| P value | 0.001 | 0.002 | <0.0001 | NR | ||||
1L, first line; ≥2L, second and later line; a/m, advanced/metastatic; CI, confidence interval; DCR, disease control rate; EC, external control; HR, hazard ratio; INV, investigator; MTC, medullary thyroid cancer; NR, not reached; OR, odds ratio; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PSM, propensity score matching; RET, gene encoding rearranged during transfection protein; RWD, real-world data; SoC, standard of care.
Calculated using the reverse Kaplan–Meier method.
The generalised Hessian matrix was not a positive definite matrix; the iteration was terminated, and the standard error of the parameter estimates was not output. Although the parameter estimates were available, they should not be used for inference.