Wimberger 2010.
| Study characteristics | ||
| Methods | Retrospective data set review (retrieved from 3 prospective, randomised phase III trials: AGO‐OVAR (OVAR‐3/‐5/‐7)) | |
| Participants | Cohort of women from three prospective, randomised phase III trials: AGO‐OVAR (OVAR‐3/‐5/‐7) in between 1995 and 2002 Previously untreated epithelial ovarian cancer FIGO stage IV, at least 18 years of age and required to have adequate haematologic, renal and hepatic function, defined as follows: absolute neutrophil count (ANC) of at least 1.5 × 109 cells/L, platelet count of at least 100 × 109 cells/L, serum creatinine and bilirubin of no more than 1.25 × upper normal limit N = 573, all FIGO stage IV disease: malignant pleural effusion = 214 (37.3%), parenchymal hepatic metastases = 146 (25.5%), other sites disease = 213 (37.2%) Median age was 59 years (range 19 to 83); age < 50 (17.6%), 50 to 65 (59.5%), > 65 (22.9%) ECOG performance status: 0 (28.2%), 1 (54.6%), 2 (17.2%) Histological subtypes; serous (68.2%), endometrioid: (6.9%), mucinous (16.0%) Peritoneal carcinomatosis: yes (87.8%), no (12.2) France and Germany |
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| Residual disease details | Residual disease were defined as:
Women were randomly assigned to one of two treatment arms consisting of either carboplatin or cisplatin and paclitaxel, or a combination of carboplatin and paclitaxel versus the same combination with epirubicin or topotecan. All women were scheduled to receive at least 6 courses of platinum‐taxane intravenously every 3 weeks. |
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| Outcomes |
Women with stage IV Kaplan‐Meier Median OS (unadjusted) of NMRD 54.6 months, SVRD 25.8 months, LVRD > 1 cm 23.9 months Median PFS (unadjusted) of NMRD 19.1 months, SVRD 13.6 months, LVRD (> 1 cm) 11.3 months Multivariant analysis for OS: SVRD vs NMRD: HR 1.87 (95% CI 1.21 to 2.89) LVRD (> 1 cm) vs NMRD: HR 2.13 (95% CI 1.40 to 3.23) Multivariate analysis for PFS: SVRD vs NMRD: HR 1.51 (95% CI 1.05 to 2.19) LVRD (> 1 cm) vs NMRD: HR 1.82 (95% CI 0.28 to 2.59) HRs adjusted for age, performance status, histological type, presence of peritoneal carcinomatosis and multiple sites (Y/N) |
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| Risk of bias (QUIPS) | 1. Study participation (a‐f): low risk Adequate number of participants and description of target population. Baseline characteristics, eligibility criteria, sampling frame and period/place study took place presented clearly. 2. Study attrition (a‐e): unclear risk Unclear if patients with incomplete follow‐up were excluded before arriving at the stated sample size. Insufficient information to permit judgement. 3. Prognostic factor measurement (a‐f): low risk Valid and reliable measurement of RD Outcome level assessment: Outcome: overall survival 4. Outcome measurement (a‐c): low risk Valid and reliable measurement of outcome 5. Adjustment for other prognostic factors (a‐g): unclear risk Age arbitrarily categorised. Multivariate model for OS adjusted for age, ECOG, histology, peritoneal carcinomatosis and number of stage IV disease sites 6. Statistical analysis and reporting (a‐d): high risk No conceptual framework; unclear of variable selection criteria for multivariate analysis Outcome: progression‐free survival 4. Outcome measurement (a‐c): low risk Valid and reliable measurement of outcome 5. Adjustment for other prognostic factors (a‐g): unclear risk Age arbitrarily categorised. Multivariate model for PFS adjusted for age, ECOG, histology, peritoneal carcinomatosis and number of stage IV disease sites 6. Statistical analysis and reporting (a‐d): high risk No conceptual framework; unclear of variable selection criteria for multivariate analysis |
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| Notes | All women with stage IV disease in 3 RCTs: OVAR‐3 trial (1995 to 1997): 69 women received carboplatin‐paclitaxel (7 women had complete resection) 64 women received cisplatin‐paclitaxel (6 women had complete resection) OVCAR‐5 trial (1997 to 1999: 112 carboplatin‐paclitaxel (14 complete resection, 61 LVRD > 1 cm) 106 carboplatin‐paclitaxel‐epirubicin (12 complete resection, 63 LVRD > 1 cm) OVCAR‐7 trial (1999 to 2002): 104 carboplatin‐paclitaxel (15 complete resection) 118 carboplatin‐paclitaxel‐topotecan (15 complete resection) The difference in proportion of women with zero residual disease in all 3 trials is not statistically significant (OVAR‐3, P = 0.88, OVAR‐5 P = 0.79 and OVAR‐7, P = 0.71). No significant trend difference in women recruited during the different time period. No relation between residual disease and the number of applied chemotherapy cycles. Therefore, all 3 trials were considered sufficiently similar to be combined for this study and analysis. Median OS was statistically reduced in FIGO stage IV 26.1 months compared to stage IIIC |
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