Table 7.
Summary of overall survival in patient subgroups.
| Study sample | Unweighted sample | IPTW-Weighted samplea | ||||||
|---|---|---|---|---|---|---|---|---|
| Avapritinib | BAT | Estimate | p | Avapritinib | BAT | Estimate | p | |
| (95% CI)d | (95% CI) | |||||||
| Subgroup 1: Avapritinib vs. BAT, 1L | ||||||||
| Number of lines of therapy (number of unique patients)b | 66 (66) | 118 (118) | 62 (62) | 115 (115) | ||||
| Median OS (months) (95% CI) | 46.9 (46.9, NE) | 27.0 (20.0, 44.3) | – | – | 49.0 (29.6, NE) | 27.0 (19.7, 44.3) | – | – |
| HR (95% CI)c | – | – | 0.50 (0.28, 0.87) | 0.014* | – | – | 0.40 (0.22, 0.74)d | 0.003* |
| Subgroup 2: Avapritinib (≤200 mg) vs. BAT, 1L+ | ||||||||
| Number of lines of therapy (number of unique patients)b | 136 (136) | 222 (141) | 133 (133) | 212 (135) | ||||
| Median OS (months) (95% CI) | NR (49.0, NE) | 23.4 (19.5, 32.6) | – | – | 49.0 (49.0, NE) | 26.8 (19.5, 37.2) | – | – |
| HR (95% CI)c | – | – | 0.37 (0.23, 0.60) | <0.001* | – | – | 0.43 (0.26, 0.72)e | 0.001* |
| Subgroup 3: Avapritinib (≤200 mg) vs. BAT, 2L+ | ||||||||
| Number of lines of therapy (number of unique patients)b | 85 (85) | 104 (73) | 83 (83) | 95 (64) | ||||
| Median OS (months) (95% CI) | NR (NE, NE) | 20.3 (14.9, 33.9) | – | – | NR (NE, NE) | 17.9 (14.8, 36.5) | – | – |
| HR (95% CI)c | – | – | 0.32 (0.17, 0.60) | <0.001* | – | – | 0.34 (0.17, 0.69)f | 0.003* |
| Subgroup 4: Avapritinib (200 mg) vs. BAT, 2L+ | ||||||||
| Number of lines of therapy (number of unique patients)b | 79 (79) | 104 (73) | 77 (77) | 96 (66) | ||||
| Median OS (months) (95% CI) | NR (NE, NE) | 20.3 (14.9, 33.9) | – | – | NR (NE, NE) | 17.2 (14.6, 36.5) | – | – |
| HR (95% CI)c | – | – | 0.39 (0.21, 0.74) | 0.004* | – | – | 0.37 (0.18, 0.75)g | 0.006* |
| Subgroup 5: Avapritinib PATHFINDER (200 mg) (RAC-RE population) vs. BAT, 2L+ | ||||||||
| Number of lines of therapy (number of unique patients)b | 47 (47) | 104 (73) | 41 (41) | 99 (67) | ||||
| Median OS (months) (95% CI) | NR (NE, NE) | 20.3 (14.9, 33.9) | – | – | NR (17.5, NE) | 17.2 (14.6, 33.9) | – | – |
| HR (95% CI)c | – | – | 0.52 (0.26, 1.03) | 0.060 | – | – | 0.47 (0.21, 1.09)h | 0.080 |
| Subgroup 6: Avapritinib PATHFINDER (200 mg) (Safety population) vs. BAT, 2L+ | ||||||||
| Number of lines of therapy (number of unique patients)b | 67 (67) | 104 (73) | 66 (66) | 97 (67) | ||||
| Median OS (months) (95% CI) | NR (NE, NE) | 20.3 (14.9, 33.9) | – | – | NR (17.4, NE) | 17.9 (14.8, 36.5) | – | – |
| HR (95% CI)c | – | – | 0.40 (0.20, 0.81) | 0.010* | – | – | 0.49 (0.20, 1.23)i | 0.127 |
1L first line of therapy, 1L+ first or later line of therapy, 2L+ second or later line of therapy, AdvSM advanced systemic mastocytosis, BAT best available therapy, CI confidence interval, ECOG Eastern Cooperative Oncology Group, HR hazard ratio, IPTW inverse probability of treatment weighting, NE not estimable, NR not reached, RAC-RE response assessment committee-response evaluable.
*p < 0.05.
aStabilized weights were generated using the following baseline characteristics: age, sex, region, ECOG score, anemia (hemoglobin <10 g/dl), thrombocytopenia (platelet count <100 × 109/l), AdvSM subtype, skin involvement, leukocyte count of 16 × 109/l or higher, serum tryptase level of 125 ng/ml or higher, number of mutated genes within the SRSF2/ASXL1/RUNX1 gene panel.
bEffective sample size for the number of lines of therapy and number of unique patients were reported for the weighted population.
cBoth unweighted and IPTW-weighted Cox proportional hazards models with a robust sandwich variance estimator were used to model overall survival. IPTW-weighted Cox proportional hazards model further adjusted for covariates with a standardized difference of greater than 10% after weighting, using a doubly robust approach. HR and the corresponding 95% CI and p value were presented. Two-sided p value <0.05 was considered statistically significant without multiplicity adjustment.
dIPTW-weighted multivariable Cox proportional hazards model further adjusted for age, ECOG score, AdvSM subtype, and skin involvement.
eIPTW-weighted multivariable Cox proportional hazards model further adjusted for region, presence of thrombocytopenia at baseline, serum tryptase level of 125 ng/ml or higher, and prior use of tyrosine kinase inhibitor therapy.
fIPTW-weighted multivariable Cox proportional hazards model further adjusted for sex, region, ECOG score, presence of thrombocytopenia at baseline, leukocyte count of 16 × 109/l or higher, prior use of tyrosine kinase inhibitor therapy, and prior use of cytoreductive therapy.
gIPTW-weighted multivariable Cox proportional hazards model further adjusted for sex, region, ECOG score, presence of thrombocytopenia at baseline, leukocyte count of 16 × 109/l or higher, serum tryptase level of 125 ng/ml or higher, prior use of tyrosine kinase inhibitor therapy, and prior use of cytoreductive therapy.
hIPTW-weighted multivariable Cox proportional hazards model further adjusted for sex, region, presence of anemia at baseline, presence of thrombocytopenia at baseline, AdvSM subtype, prior use of tyrosine kinase inhibitor therapy, and prior use of cytoreductive therapy.
iIPTW-weighted multivariable Cox proportional hazards model further adjusted for age, region, ECOG score, presence of thrombocytopenia at baseline, leukocyte count of 16 × 109/l or higher, serum tryptase level of 125 ng/ml or higher, and prior use of tyrosine kinase inhibitor therapy.