Gershanovich 1997.
| Study characteristics | ||
| Methods | Design: A multicentre, randomised, open‐label, phase III trial Centres: Moscow (Russia), St. Petersburg (Russia), Riga (Latvia), and Tallinn (Estonia) Accrual: From February 1987 to March 1992 Randomisation: The treatments were randomised and the study drug containers were pre‐numbered separately for measurable and non‐measurable strata. The patients were given a study number with respective study drug in the order of accrual Baseline comparability: The pretreatment characteristics of the patients are evenly balanced among the treatment arms |
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| Participants | 463 postmenopausal women with histologically or cytologically verified, previously untreated, inoperable primary, residual, metastatic, or recurrent breast cancer that was ER‐positive or ER‐unknown ER‐status: 142 (30.7%) positive; 13 (2.8%) negative; 308 (66.5%) unknown Age (median and range): Arm A, 60.9 (38.0 to 85.0); arm B, 62.2 (35.0 to 82.0); arm C, 59.6 (31.0 to 90.0) |
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| Interventions | Arm A (n = 157): one toremifene 60 mg tablet daily (TOR60) Arm B (n = 157): two toremifene 60 mg tablets twice a day (TOR240) Arm C (n = 149): one tamoxifen 40 mg tablet daily (TAM40) |
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| Outcomes | Response Time to progression Overall survival Time to treatment failure Response duration Safety Quality of life |
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| Notes | Median follow‐up time was 20.5 months. 404 (87.3%) patients were evaluable and eligible ITT analysis was used. The results of ITT analysis and that of evaluable patients analysis were similar in terms of response rate and time to progression. For other outcomes, no mention was made in this respect 27 (17%) patients in TOR60, 30 (19%) patients in TOR240, and 32 (22%) patients in TAM40 discontinued the study prematurely 122 (77.7%) patients in TOR60, 116 (73.9%) patients in TOR240, and 115 (77.2%) patients in TAM40 progressed at the time of data cut‐off. Median time to progression was 4.9 (3.8 to 7.3) months in TOR60, 6.1 (4.5 to 8.0) months in TOR240, and 5.0 (3.7 to 6.2) months in TAM40. The HR for TOR60 vs TAM was 0.99 (95% CI: 0.77 to 1.27). The HR for TOR240 vs TAM40 was 0.89 (95% CI: 0.69 to 1.19) 97 (61.8%) patients in TOR60, 96 (31.4%) patients in TOR240, and 89 (59.7%) patients in TAM40 died at the time of data cut‐off. Deaths on study, including the causes of deaths, were not significantly different among the treatment arms. Median overall survival was 25.4 (20.8 to 31.0) months in TOR60, 23.8 (20.9 to 29.7) months in TOR240, and 23.4 (18.4 to 34.2) months in TAM40. The HR for TOR60 vs TAM40 was 1.04 (95% CI: 0.78 to 1.39). The HR for TOR240 vs TAM40 was 0.98 (95% CI: 0.73 to 1.31) |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Although no information was provided on how the random sequence was generated, the baseline characteristics were comparable between the treatment arms |
| Allocation concealment (selection bias) | Low risk | Although no information was provided on whether the allocation was concealed, the baseline characteristics were comparable between the treatment arms |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Although this is an open‐label trial, all the efficacy outcomes and most of the safety outcomes used in the present meta‐analysis are objective, not subjective. They were unlikely to have been biased by patients' awareness of their treatment status |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | This is an open‐label trial. It is unknown whether the outcome assessment had been biased by the assessors' awareness of the treatment allocation |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Data for every prespecified outcome were completely reported |
| Selective reporting (reporting bias) | Low risk | Data for every prespecified outcome were completely reported |
| Other bias | Low risk | No other apparent source of bias was identified |