The degree of oestrogen receptor (ER) expression in ovarian cancer correlates well with its endocrine sensitivity. However, the use of endocrine therapy (ET) in relapsed disease is variable in part due to the lack of phase III data. It is thus unlicensed and not a standard of care. Here we describe the endocrine sensitivity of high grade serous ovarian carcinoma (HGSOC) in a large retrospective cohort.
Patients were eligible if they had HGSOC treated with prior chemotherapy, and received at least 4 weeks of ET. Exclusion criteria included: ET as a maintenance treatment and unknown duration of therapy (DOT). The best CA125 response across the DOT was recorded as per modified GCIG criteria. Stable CA125 response had to be maintained for at least 12 weeks. The primary endpoint was DOT. Secondary endpoints were time to next therapy (TTNT) from treatment initiation, CA125 objective response rate (ORR) and clinical benefit rate (CBR).
593 patients were identified from the Edinburgh Ovarian Cancer Database between January 1974 and December 2015. 267 patients met the eligibility criteria (78.3% letrozole, 19.5% tamoxifen, 2.2% megestrol acetate). Median DOT and TTNT were 122.5 days (range 28-1427 days) and 161 days (range 41-2345 days), respectively. 33.2% and 14.6% of patients received ET for ≥ 180 and ≥ 365 days, respectively. Of 38 patients on ET for ≥ 365 days, 29 (76%) received ET as 2nd line therapy, 9 (24%) as 3rd line therapy and none as 4th line or later. The CA125 ORR and CBR in evaluable pts was 11.4% (20/175) and 48.6% (85/175), respectively. The CA125 CBR, median DOT and TTNT between different ER histoscore ranges are compared in Table. In early (2nd line) vs late (3rd line onwards) use of ET, the median DOT and TTNT was 140 vs 98 days (HR = 0.68 [95% CI 0.53-0.87]) and 167 vs 138 days (p = 0.022), respectively.Table:
|ER histo-score||CA125 CBR (%)||DOT (days)||Median TTNT (days)|
|≥150 vs |
The endocrine sensitivity of HGSOC is significantly influenced by the degree of ER expression and line of treatment that ET is used in. Early introduction of ET in the management of relapsed HGSOC should be considered particularly in tumours with an ER histoscore of ≥ 200.
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Professor Charlie Gourley
M. MacKean: For the last 10 years; Ad boards: Tessaro, Bristol-Myers Squibb, Roche, Boehringer Ingelheim, Eli Lily and Glaxo Smith Kline. F. Nussey: Has been the local principle investigator for the SOLO 2 trial (randomised phase III trial of maintenance Olaparib in BRCA mutant patients). C. Gourley: AstraZeneca (advisory board, lecture fees, research funding); Clovis (advisory board); Tesaro (advisory board, lecture fees), Roche (advisory board); Novartis (research funding), Nucana (advisory board, research funding) and Aprea (research funding). All other authors have declared no conflicts of interest.