IMPROVING CANCER CARE, ONE SLIDE AT A TIME
The GOC News | Spring 2019
BRCA Collaborative Advocating for National Tumour Testing in Ovarian Cancer
BY DR. JANICE KWON, CO-CHAIR
The National BRCA Collaborative was established to align six professional societies (GOC, Canadian Association of Pathologists, Canadian College of Medical Geneticists, Canadian Association of Genetic Counselors, and Canadian Association of Nurses in Oncology) with the intent to improve genetic testing rates for BRCA mutations, as well as therapeutic interventions for these high-risk individuals. The BRCA Collaborative first convened in May 2018, and then presented to the GOC membership at the BRCA CoP meeting in November 2018. The focus of that meeting was the role of tumour testing for BRCA mutations in ovarian cancer. Although all women in Canada with high-grade serous ovarian cancer are eligible for genetic testing for BRCA mutations (and in many jurisdictions, all non-mucinous epithelial ovarian cancer), many women remain untested. One of the barriers is the shortage of genetic counselors and lengthy wait times for consultation, which can take up to two years. The Mainstreaming model (referral for germline testing initiated by the oncologist) can improve the referral process efficiency by reducing the number of referrals to genetic counseling and reducing the wait times for genetic testing results. However, not all centres have adopted this model and many ovarian cancer patients remain untested. Furthermore, even if all eligible women were tested, some will have a somatic (sporadic) mutation that will be missed by germline testing. Women with either a germline or somatic mutation could benefit from treatment with a PARP inhibitor. Tumour testing (sequencing ovarian cancer tissue to identify genetic mutations) could identify somatic mutations. Confirmatory germline testing is still required to determine which of these women have somatic mutations only in the tumour vs. germline mutations that could be passed down through generations. There is limited data on the sensitivity of tumour testing for identifying germline mutations, but if proven to be highly sensitive, tumour testing could serve as a triage for confirmatory germline testing. This would save resources and costs by reducing the need for genetic counseling and germline testing.
The results of SOLO1 were published in late 2018. This was a multicentre prospective clinical trial comparing maintenance PARP inhibitor (olaparib) to standard of care (no further treatment) after completion of first-line chemotherapy for advanced ovarian cancer in confirmed BRCA mutation carriers. There was a three-year difference in PFS between the two groups (three-year PFS 60% vs. 27% for olaparib vs. placebo, respectively). Furthermore, olaparib was well tolerated. This magnitude of benefit is unprecedented in advanced ovarian cancer, and the BRCA Collaborative highly recommends that maintenance olaparib should be adopted as the standard of care. Cancer Care Ontario has implemented reflex BRCA tumour testing for all advanced ovarian cancer cases at UHN/Mt. Sinai since August 2018. This testing requires clinicians to discuss germline and tumour testing at their patients’ initial visit, and the implications of testing. If BRCA mutation is in the tumour, then they are eligible for PARP inhibitor AND referral for germline testing because of downstream cancer prevention for family members. Many other centres in Canada have pathology labs that are in the process of acquiring accreditation for tumour testing in ovarian cancer. Many of these labs are already sequencing other types of tumours (such as colorectal, low-grade glioma, melanoma). We need closer collaboration amongst multiple disciplines (gynecologic oncology, pathology, genetics), as well as development of patient education and consent materials for systematic implementation of tumour testing. Astra Zeneca had initially pledged to provide funding for tumour testing for eligible ovarian cancer cases across Canada until March 31, 2019. These cases were to be sent to Toronto (UHN/Mt. Sinai) for testing. The intent was to allow other health care centres to become familiar with the process of tumour testing in ovarian cancer, but ultimately assume the responsibility and costs of this testing. As of March 2019, only 12 cases had been submitted to Toronto for testing. Potential reasons for the low testing rate include: (1) lack of knowledge among gynecologic oncologists across Canada, and (2) unfamiliarity
A word from GOC’s 20th President – Dr. James Bentley CONTINUED FROM PAGE 1 experience in major debulking surgery in the pelvis and upper abdomen. Dr. Taymaa May has been working hard with the AGM Program Planning Committee to put this innovative program together. Also in June, it will be my great pride and pleasure to presentaGOCPresidentialMedaltooneofmymentors and all-time favorite gynecologic oncologists, Dr. Robert Lotocki. For many of us Bob exemplifies what it is to be a true academic gynecologic oncologist. The medal will be awarded at the Awards Dinner at Casino Nova Scotia, along with other notable recognitions; it will be a night to remember. Going forward, GOC is in the process of drafting a position statement highlighting the importance of tumour testing in ovarian cancer. This position statement could be leveraged by gynecologic oncologists for acquisition of funding for tumour testing infrastructure at their own institutions. Olaparib is currently sanctioned for use by Health Canada in platinum-sensitive recurrent ovarian cancer, but still requires approval for the specific indication of maintenance therapy after first-line treatment. Upon approval for this indication, it will be even more important to have tumour testing readily available to all ovarian cancer patients. among pathologists about how to process/transfer slides to Toronto for tumour testing. The BRCA Collaborative has pledged to address these barriers, by providing specific details about this tumour testing initiative at the GOC CPD meeting in May 2019, and by delegating a representative to the CAP (Canadian Association of Pathologists) annual general meeting in June 2019 in Niagara Falls to describe the logistics of processing and sending samples/slides for tumour testing in Toronto. Astra Zeneca has offered to extend the deadline for tumour testing until November 30, 2019.
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