Hormonal therapy for epithelial ovarian cancer: a systematic review and meta-analysis of phase II studies

Background

Endocrine therapy is a common clinical practice in epithelial ovarian cancer (EOC) and hormonal receptors have been associated with response and survival in recent studies. However, the degree of activity of endocrine therapy overall and by specific agents remains unclear.

Methods

Objective response rates (ORR) from phase II trials of different hormonal manipulations in EOC patients were meta-analyzed. Pooled estimates (PES) from random effect models were calculated according to type of intervention, ER/PgR status, tamoxifen dose, year of study and platinum resistance. Two randomized trials were excluded from analysis given their low number.

Results

The analyses encompassed a total of 35 phase II trials including 1.690 patients. Overall, we obtained a PES = 0.37 [95%CI, 0.28-0.46] with any endocrine treatment. By specific agent class, PES was = 0.31 [95%CI, 0.23-0.39] for aromatase inhibitors, 0.40 [95%CI, 0.21-0.58] for tamoxifen, 0.41 [95%CI, 0.23-0.59] for estro-progestins, 0.39 [95%CI, 0.25-0.52] for tamoxifen plus progestins, 0.30 [95%CI, 0.20-0.40] for progestins, 0.14 [95%CI, 0-0.58] for the anti-androgen flutamide, 0.50 [95%CI, 0.31-0.69] for tamoxifen plus goserelin, 0.52 [95%CI, 0.32-0.72] for the ER downregulator fulvestrant, even though the last three categories included only one study each. The PES was better in studies including patients with ER + ve or PgR + ve disease [PES= 0.43, 95%CI, 0.34-0.52] compared with hormone receptor -ve [PES= 0.17, 95%CI, 0.09-0.24] or mixed [PES= 0.31 95%CI, 0.17-0.46] disease. High tamoxifen doses (>20 mg/day) exhibited a worse PES= 0.36 [95%CI, 0.16-0.57] than the standard dose of 20 mg/day (PES = 0.50 [95%CI, 0.13-0.87]. A slightly better response was noted in platinum resistant [PES= 0.35, 95%CI, 0.19-0.50] vs platinum sensitive patients [PES= 0.43, 95%CI, 0.3-0.57]. There was no evidence for a response trend by year of study.

Conclusions

The activity of endocrine therapy in advanced EOC looks promising but has not adequately been evaluated in definitive clinical trials. Given the recent evidence for a prognostic value of hormone receptors in EOC, our findings support the implementation of randomized trials in hormone receptor positive EOC.

Clinical trial identification

Legal entity responsible for the study

E.O. Galliera

Funding

Italian Association for Cancer Research (AIRC)

Disclosure

All authors have declared no conflicts of interest.