1538 – Tumour testing to detect somatic BRCA1 or BRCA2 gene mutations, in patients with platinum-sensitive, relapsed high-grade serous ovarian cancer (HGSOC), to determine eligibility for PBS olaparib

New MBS item

Germline BRCA1/2 testing to determine eligibility for olaparib maintenance therapy in patients with platinum-sensitive, relapsed high-grade serous ovarian cancer (HGSOC) has been listed on the MBS (item 73295) and PBS (items 11034R and 11050N) since 1 February 2017 (refer co-dependent MSAC/PBAC Application 1380). Subsequently, germline gene mutation testing (including BRCA1/2 testing from the time of diagnosis in ovarian cancer patients at >10% risk of having a pathogenic mutation) became available on the MBS in November 2017 (Item 73296). Significant changes to the local and international tumour BRCA1/2 mutation testing environment (and additional outcome data - published and unpublished) warrants reconsideration of tumour testing for patients with somatic BRCA1/2 mutations.

Tumour testing to detect somatic BRCA1/2 gene mutations is proposed to occur after germline BRCA1/2 testing. There are two populations as follows:

• Patients with platinum-sensitive, relapsed HGSOC, who were germline BRCA1/2 wild-type when first tested under MBS item 73295; OR
• Patients with HGSOC who received germline BRCA1/2 testing under item 73296 and were found to be gBRCA1/2 mutation wild-type (who are platinum-sensitive and relapsed after platinum chemotherapy).

HGSOC patients who have no germline BRCA1/2 gene mutation, but have a somatic BRCA1/2 gene mutation, are not currently eligible for olaparib treatment. It is proposed these patients should be eligible for olaparib treatment after completion of two lines of platinum chemotherapy and a response (complete or partial) after a platinum-free interval of 6 months or greater. Patients who test wild-type for somatic BRCA1/2 gene mutations would be categorised as 'watch and wait' and receive no active anti-cancer treatment.

Type: Co-dependent technology

Ovarian cancer is the eighth most commonly diagnosed type of cancer for women in Australia, with an estimated 1613 new cases in 2018. The 5-year relative survival for women with ovarian cancer in Australia is low at 44.4%. The most common and most aggressive histological subtype is high-grade serous ovarian cancer (HGSOC). Patients with fallopian tube or primary peritoneal cancer have similar serous features and are usually treated as for ovarian cancer. HGSOC is difficult to diagnose in its early stages as there are no effective tests for early detection, and symptoms tend to be vague and non-specific (e.g. bloating, fatigue and abdominal pain) so most women are diagnosed when their disease is advanced and widespread. Standard first line treatment of HGSOC is platinum-based chemotherapy. Ovarian cancer is a highly chemo-sensitive tumour type, but more than 70% of women with advanced disease initially responding to first-line chemotherapy will eventually relapse and require re-treatment. BRCA1 and BRCA2 mutational loss of function is a primary driver of ovarian cancer. The HGSOC population who have platinum sensitive, relapsed disease is enriched for patients with BRCA1/2 germline and somatic mutations, in comparison to all ovarian cancer patients.

• PASC meeting: 9 August 2018
• ESC meeting: -
• MSAC meeting: -