eUpdate – Ovarian Cancer Treatment Recommendations
Published: 21 September 2016. Authors: J.A. Ledermann1, C. Sessa2 & N. Colombo3 on behalf of the ESMO Guidelines Committee
1UCL Cancer Institute, University College London, London; 2Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland; 3European Institute of Oncology, University of Milan Bicocca, Milan, Italy.
Clinical Practice Guidelines
This update refers to the Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Ledermann JA, Raja FA, Fotopoulou C et al, Ann Oncol 2013; 24 (Suppl 6): vi24-vi32.
Maintenance therapy with the oral PARP inhibitor, olaparib has been approved by the European Medicines Agengy in women with high grade serous ovarian cancer and a BRCA mutation who have responded to platinum-based chemotherapy. In the randomised placebo-controlled maintenance trial, study 19, the median progression-free survival was extended from 4.3 to 11.6 months, post randomisation hazard ratio [HR] 0.18; p<0.0001) . An updated survival analysis in patients with either a germline or somatic BRCA mutation showed an improvement in median survival from 30.2 to 34.9 months (HR 0·62 [95% CI 0·41–0·94]). Because of the effect of previous analyses, this difference was not statistically significant. Among the patients with a BRCA mutation, 15% remained on olaparib for at least five years without evidence of any tumour progression . A BRCA mutation is the first genetically defined predictive marker for treatment of ovarian cancer.
- Patients with recurrent high-grade serous ovarian cancer and a germline or tumour BRCA mutation should be offered maintenance olaparib after a response to platinum-based chemotherapy.
Testing for a BRCA mutation
BRCA mutations are found in 5%-15% of ovarian cancer population studies . Cohort studies have shown that the absence of a family history of breast/ovarian cancer is a poor negative predictor for a BRCA mutation [4, 5]. It is now recommended that patients with high-grade tumours are tested for germline BRCA mutation. Somatic mutations of BRCA are found in 5%-7% of ovarian cancer cases .
- Patients with high-grade tumours should be tested for a germline BRCA mutation. Consideration should be given to testing tumours for a somatic BRCA mutation.
- Ledermann JA, Harter P, Gourley C et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 2014; 15: 852-861.
- Ledermann JA, Harter P, Gourley C et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: An updated analysis from a Phase II, randomised, double-blind, placebo-controlled trial. Lancet Oncol 2016. Epub ahead of print.
- Ramus SJ, Gayther SA. The contribution of BRCA1 and BRCA2 to ovarian cancer. Mol Oncol 2009; 3: 138-150.
- Alsop K, Fereday S, Meldrum C et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 2012; 30: 2654-2663.
- Daniels MS, Babb SA, King RH et al. Underestimation of risk of a BRCA1 or BRCA2 mutation in women with high-grade serous ovarian cancer by BRCAPRO: a multi-institution study. J Clin Oncol 2014; 32: 1249-1255.
- Moschetta M, George A, Kaye SB, Banerjee S. BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Ann Oncol 2016; 27: 1449-1455.