Original Article Table 2. Univariate Overall Survival Analyses
Variable
No. of Patients
No. of Deaths
3-Year OS rate (95% CI), %
Median Survival (95% CI), y
All
190
73
75.8 (67.7-82.1)
5.4 (4.2-5.9)
143 30 17
60 10 3
69.4 (59.4-77.3) 90.7 (67.6-97.6) 100
4.3 (3.6-5.5) 5.6 (3.5-Not estimable) Not reached
HR (95% CI)
LogRank P
Ref 0.61 (0.31-1.2) 0.19 (0.06-0.62)
.005a
1.38 (1.08-1.77)
.01
BRCA mutation status BRCA negative BRCA1 positive BRCA2 positive Age at diagnosis; 10-y HR
Stage III IV
148 42
58 15
79.7 (70.9-86.1) 60.3 (39.4-76.1)
5.4 (4.3-6.0) 3.5 (2.7-Not estimable)
Ref 1.29 (0.73-2.29)
.38
44 144
23 50
45.6 (27.2-62.3) 70.6 (60-78.9)
3.0 (1.7-4.0) 4.9 (3.7-5.8)
Ref 0.5 (0.31-0.82)
.005
94 93
47 26
58.1 (45.3-69) 74.2 (60.3-83.9)
3.7 (2.7-5.0) 5.0 (3.8-Not Estimable)
Ref 0.51 (0.32-0.83)
.005
Optimal debulkingb No Yes
IP/IVc IV IP
Abbreviations: BRCA1/BRCA2, breast cancer genes 1 and 2, respectively; BRCA negative, negative for mutations in both BRCA genes; CI, confidence interval; HR, hazard ratio; IP, combined intravenous and intraperitoneal therapy; IV, intravenous therapy alone; OS, overall survival; Ref, reference level. a The log-rank P value was .150 for BRCA1 positive vs BRCA negative, .003 for BRCA2 positive vs BRCA-negative, and .050 for BRCA1 positive vs BRCA2 positive. b Two patients were excluded from the landmark analysis. c Two patients were missing information, and 1 patient was excluded from the landmark analysis.
Table 3. Multivariate Overall Survivala
Variable
HR (95% CI)
Age at diagnosis; 10-y HR BRCA1 positive vs BRCA negative BRCA2 positive vs BRCA negative Optimal vs suboptimal debulking
1.32 0.70 0.20 0.60
(1.02-1.71) (0.36-1.38) (0.06-0.65) (0.36-1.00)
P .035 .31 .007 .050
Abbreviations: BRCA1/BRCA2, breast cancer genes 1 and 2, respectively; BRCA negative, negative for mutations in both BRCA genes; CI, confidence interval; HR, hazard ratio. a Landmark analysis was used to build this multivariate model.
Figure 1. Kaplan-Meier curves illustrating overall survival for patients with breast cancer gene (BRCA)-negative, BRCA1-positive, and BRCA2-positive high-grade serous ovarian cancer.
interval [CI], 1.08-1.77), optimal debulking status (HR, 0.50; 95% CI, 0.31-0.82), and IP therapy (HR, 0.51; 95% CI, 0.32-0.83) were statistically significant predictors of survival. Surgical stage (III vs IV) was not associated significantly with survival, although the majority of
3706
patients had stage III disease (78%; 148 of 190 patients). When BRCA mutation status (BRCA1-positive, BRCA2positive, and BRCA-negative) was examined in univariate fashion, BRCA2 mutations (HR, 0.19; 95% CI, 0.060.62), but not BRCA1 mutations (HR, 0.61; 95% CI, 0.31-1.20), were a significant predictor of OS (Figure 1). The effect of BRCA mutation status on OS also was evaluated in a multivariate analysis. The results are presented in Table 3. By using a forward-selection technique, the covariates age, optimal versus suboptimal debulking, and BRCA mutation status were selected for inclusion in the final multivariate model. The type of first-line therapy was not included, because it did not reach statistical significance in the final model. This probably was because of the substantial correlation between debulking status and
Cancer
August 1, 2012