Clinical benefit and risk of death with endocrine therapy in ovarian cancer: A comprehensive review and meta-analysis

Abstract

Background: Steroid hormones promote epithelial ovarian cancer (EOC) growth and their receptor expression is associated with disease outcome. Hormone therapy is frequently used in pretreated EOC, but the magnitude of activity overall and by specific agents or tumor characteristics is unknown.

Methods: Clinical Benefit Rates (CBR) and deaths from clinical trials of endocrine agents were meta-analyzed. Summary estimates of CBR (SCBR) and Odd Ratio for death (SOR) were calculated according with type of drug, ER and PgR status, platinum resistance, line of therapy, tumor grade and tamoxifen dose.

Results: Fifty-three trials in 2490 patients were analyzed. Overall, SCBR was 41% (95%CI, 0.34-0.48) for any endocrine treatment, 43% (95%CI, 0.30-0.56) for tamoxifen, 39% (95%CI, 0.29-0.50) for aromatase inhibitors and 37% (95%CI, 0.26-0.48) for progestins. The SCBR for ER+ and/or PgR+ tumors was 46% (95%CI, 0.34-0.57) versus 37% (95%CI, 0.27-0.48) in tumors with unknown receptors and 55% in platinum sensitive (95%CI, 0.28-0.80) versus 40% (95%CI, 0.29-0.51) in platinum resistant tumors The SOR for death calculated from 6 out of 9 randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy (SOR=0.69, 95%CI, 0.50-0.97), with a possible tendency for a greater effect in first line and low grade tumors. The overall quality of the RCTs was low.

Conclusions: The activity of endocrine therapy in advanced EOC is worth considering and seems to support large properly designed randomized trials in the first treatment of hormone sensitive EOC.