Poster Presentation 30th Lorne Cancer Conference 2018

ALLOCATE - sorting ovarian cancer patients into treatment categories based on molecular profiling (#186)

Olga Kondrashova 1 2 , Gwo Yaw Ho 2 3 4 , George Au-Yeung 3 , Leakhena Leas 1 , Sebastian Lunke 1 , Kathryn Alsop 3 , Clare Scott 2 4 , Anne Hamilton 3 , Sumitra Ananda 5 , Ali Freimund 3 , Michael Quinn 4 , Orla McNally 4 , Tiffany Boughtwood 1 , Matthew Wakefield 1 2 , Arthur Hsu 1 , Alexander Dobrovic 1 6 , Michael Christie 1 , Graham Taylor 1 , David Bowtell 3 , Linda Mileshkin 3 , Paul Waring 1
  1. University of Melbourne, Parkville, VIC, Australia
  2. Walter and Eliza Hall Institute, Melbourne
  3. The Peter MacCallum Cancer Centre, Melbourne
  4. The Royal Women's Hospital, Melbourne
  5. The Royal Melbourne Hospital, Melbourne
  6. Olivia Newton-John Cancer Research Institute, Melbourne

Background: The Australian Ovarian Cancer Assortment Trial (ALLOCATE) was designed as a pilot study to demonstrate feasibility of genetic profiling patients with recurrent ovarian cancer with the aim of allocating patients to targeted therapies based on the genomic profile of their tumours.

Methods: Two next generation sequencing panels, one targeting 38 genes mutated in ovarian cancer and the other targeting 11 genes with copy number alterations1, as well as BRCA1 and RAD51C methylation assays, were used for molecular profiling of most common subtypes of ovarian cancer. A thorough analytical validation was performed to ensure that these tests were fit for diagnostic use.

Results: A total of 113 patients with recurrent ovarian cancer were recruited from two tertiary hospitals, with 14 cases excluded due to insufficient tumour material or poor-quality DNA. Seventy-one analysed cases in the study had high-grade serous ovarian cancer (HGSOC), and other cases included low-grade serous ovarian cancer (LGSOC), mucinous, clear cell, and mixed histology carcinomas and a metastatic carcinosarcoma.

Based on the ALLOCATE testing, two HGSOC tumours were re-classified as LGSOC, due to a lack of TP53 mutation, presence of KRAS mutation, and subsequent pathology review. Also, BRCA1/2 reversion mutations were identified in two HGSOC cases, explaining their lack of response to platinum/PARPi.

In terms of clinical utility, 6 patients (6%) received a matched therapy based on the ALLOCATE testing results. Furthermore, 7 patients (9.9%) with HGSOC, who were previously untested, were found to have a germline BRCA1/2 mutation and were subsequently referred to a familial cancer clinic for further management and testing.

­Conclusions: We demonstrated that ALLOCATE molecular profiling of recurrent ovarian cancer was feasible and reflected the known genomic characteristics of the different subtypes2. Furthermore, it resulted in clinical management changes to a number of patients. Profiling of patients earlier in their disease course and better access to targeted therapies or clinical trials may further enhance the clinical utility of molecular profiling.

  1. Kondrashova, Olga, et al. "High-throughput amplicon-based copy number detection of 11 genes in formalin-fixed paraffin-embedded ovarian tumour samples by MLPA-seq." PloS one 10.11 (2015): e0143006.
  2. Cancer Genome Atlas Research Network. "Integrated genomic analyses of ovarian carcinoma." Nature 474.7353 (2011): 609.