Response to therapy (intent-to-treat analysis set)
| Variable | Primary analysis | Final analysis | |||
| T-VEC plus ipilimumab (n=98) | Ipilimumab (n=100) | T-VEC plus ipilimumab (n=98) | Ipilimumab (n=100) | Statistical results | |
| Objective response rate (CR/PR) | 38 (39.0) | 18 (18.0) | 35 (35.7) | 16 (16.0) | 19.7 (6.8 to 31.9)* |
| 95% CI† | (26.3 to 46.0) | (9.4 to 24.7) | 0.003‡ | ||
| 2.9 (1.5 to 5.7)§ | |||||
| Best overall response | |||||
| CR | 13 (13.0) | 7 (7.0) | 20 (20.4) | 6 (6.0) | |
| PR | 25 (26.0) | 11 (11.0) | 15 (15.3) | 10 (10.0) | |
| SD | 19 (19.0) | 24 (24.0) | 20 (20.4) | 24 (24.0) | |
| PD | 31 (32.0) | 33 (33.0) | 30 (30.6) | 35 (35.0) | |
| Unevaluable | 4 (4.0) | 17 (17.0) | 7 (7.1) | 16 (16.0) | |
| Not done | 6 (6.0) | 8 (8.0) | 6 (6.1) | 9 (9.0) | |
| Disease control | |||||
| Disease control rate (CR/PR/SD) | 57 (58.0) | 42 (42.0) | 55 (56.1) | 40 (40.0) | 16.1 (1.5 to 29.9)* |
| 95% CI† | (45.7 to 66.1) | (30.3 to 50.3) | 0.033‡ | ||
| 1.9 (1.1 to 3.4)§ | |||||
| Durable response | |||||
| Durable response rate | 33 (33.7) | 13 (13.0) | 20.7 (8.2 to 32.4)* | ||
| 95% CI† | (24.4 to 43.9) | (7.1 to 21.2) | 0.001‡ | ||
| 3.4 (1.7 to 7.0)§ | |||||
| Progression-free survival (KM) (months) | |||||
| Median (95% CI) | 8.2 (4.2 to 21.5) | 6.4 (3.2 to 16.5) | 13.5 (5.2 to 25.0) | 6.4 (3.8 to 17.1) | |
| OS | |||||
| Deaths | 45 (45.9) | 52 (52.0) | |||
| Median¶ (95% CI), months | 84.9 (41.0 to NE) | 50.1 (32.0 to NE) | |||
| Estimated OS at 12 months¶, % (95% CI) | 83.3 (74.2 to 89.4) | 79.9 (70.4 to 86.7) | 3.4 (−7.6 to 14.4)* | ||
| Estimated OS at 24 months¶, % (95% CI) | 72.7 (62.5 to 80.5) | 69.3 (58.9 to 77.5) | 3.4 (−9.5 to 16.3)* | ||
| Estimated OS at 36 months¶, % (95% CI) | 62.9 (52.3 to 71.7) | 55.2 (44.5 to 64.6) | 7.7 (−6.4 to 21.8)* | ||
| Estimated OS at 48 months¶, % (95% CI) | 57.2 (46.5 to 66.5) | 50.7 (40.1 to 60.3) | 6.5 (−7.8 to 20.8)* | ||
| Estimated OS at 60 months¶, % (95% CI) | 54.7 (43.9 to 64.2) | 48.4 (37.9 to 58.1) | 6.3 (−8.1 to 20.7)* | ||
Data presented as number (%) of patients unless specified otherwise.
Confirmed CR/PR/PD per modified irRC refers to the initiating CR/PR/PD of two consecutive CR/PR/PD that are ≥4 weeks apart. The PD without confirmation was not considered as confirmed PD with only one exception: if the last tumor assessment was an initialization of PD and patients had ended radiographic follow-up due to rapid clinical deterioration.
Durable response rate was defined as the incidence rate of patients with a duration of response per modified irRC of ≥6 months; 1 month=365.25/12 days.
Progression-free survival was defined as the time from randomization to the first confirmed disease progression per modified irRC, or death.
OS was defined as the time from randomization to death from any cause.
*Rate difference (95% CI) (T-VEC plus ipilimumab−ipilimumab).
†The Clopper-Pearson method was used to calculate exact CIs for binary end points. Wilson score method with continuity correction was used to calculate an approximate CI for between-arm differences in binary rates.
‡p value from the χ2 test with continuity correction.
§Unadjusted OR (95% CI) obtained from the unstratified logistic regression model.
¶Calculated using the KM method.
CR, complete response; irRC, immune-related response criteria; KM, Kaplan-Meier; NE, not estimable; OS, overall survival; PD, progressive disease; PR, partial response; SD, stable disease; T-VEC, talimogene laherparepvec.