A new ASCO clinical practice guideline provides clinicians and other health-care professionals with evidence-based recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer.1
Christina M. Annunziata, MD, PhD
“We wanted to go over the evidence and make strong statements and recommendations about when to perform germline, somatic, and genome testing in ovarian cancer,” said Christina M. Annunziata, MD, PhD, of the National Cancer Institute, Women’s Malignancies Branch. “We saw that there were a lot of different practices going on across the community, and we wanted to get the data for the strongest recommendation that we could. There are new drugs available for specific mutations, and we wanted this guideline to ensure that all patients would get the best care.”
Although several medical societies across the globe recommend for women with ovarian cancer to receive genetic testing, about only 30% of women with this cancer undergo testing. To improve genetic testing rates in this patient population and to increase the knowledge base of oncology providers on strategies to best incorporate genetic testing into patient care, an ASCO multidisciplinary expert panel performed a systematic review of 19 observational studies, randomized controlled trials, and meta-analyses on genetic testing in epithelial ovarian cancer.
Germline testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes is recommended for all women with epithelial ovarian cancer. Although BRCA1 and BRCA2 mutations contribute to approximately 40% of ovarian cancer cases in patients with a family history of the disease, the panel recommends testing for these genes regardless of whether the patient has a family history of ovarian cancer. Additionally, somatic tumor testing for both BRCA1 and BRCA2 pathogenic or likely pathogenic variants is recommended for women without a germline pathogenic or likely pathogenic BRCA1/2 variant.
In addition, the guideline recommends testing for germline mutations at the time of disease diagnosis in an effort to guide treatment-related decision-making. In cases where women are not offered testing at the time of diagnosis, testing should be offered as soon as possible, irrespective of mutation status. For women with disease recurrence after completion of upfront therapy, somatic tumor testing for BRCA1 and BRCA2 pathogenic or likely pathogenic variants is suggested.
“There are new drugs available for specific mutations, and we wanted this guideline to ensure that all patients would get the best care.”— Christina M. Annunziata, MD, PhD
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The guideline emphasizes that offering somatic tumor testing for BRCA1 and BRCA2 pathogenic or likely pathogenic variants is particularly relevant in women who do not have a germline pathologic BRCA1/2 variant. Performing germline testing, however, does not appear to have a beneficial impact on treatment decision-making in women who have already received somatic testing.
Clinicians are urged to offer U.S. Food and Drug Administration (FDA)-approved treatments under their labeled indication and in the upfront and recurrent settings to women with epithelial ovarian cancer and germline or somatic pathogenic or likely pathogenic variants in BRCA1 and BRCA2 genes. Women with advanced cancer and a germline mutation qualify for PARP (poly [ADP-ribose] polymerase) inhibitor maintenance therapy, such as olaparib, after achieving a response to initial chemotherapy. PARP inhibitors have been associated with higher rates of response in patients with BRCA1/2 pathogenic or likely pathogenic variants. This result is based on data from the SOLO1 trial, which found improved response rates with olaparib monotherapy as maintenance in the front-line setting in newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with BRCA1 and/or BRCA2 mutations.
In women with clear cell, mucinous, or endometrioid ovarian cancer, the guideline recommends offering somatic tumor testing for mismatch repair deficiency (dMMR). Women with other histologic epithelial ovarian cancer types may also be recommended for dMMR testing, based on evidence suggesting that the identification of a dMMR phenotype/genotype can guide clinical decisions about the use of pembrolizumab, particularly in the setting of recurrent disease. The ASCO guideline recommends that clinicians offer FDA-approved treatment under their labeled indication in women with recurrent epithelial ovarian cancer and dMMR.
Dr. Annunziata emphasized that no data exist to support a recommendation for routine tumor testing with homologous recombination–deficiency assays.
Improving Awareness of Recommendations
Although the new recommendations will be distributed through the ASCO Practice Guideline Implementation Network, the expert panel suggests that a barrier to implementation in clinical practice will be the need to improve awareness of the recommendations among cancer survivors, their caregivers, and first-line clinicians. The expert panel added that future research involving molecular alterations and their impact on directing therapeutic decision-making may help shape future updates to the guideline.
According to Dr. Annunziata, the current guideline represents the best evidence available to date. “With this guideline, we need to try to influence practice and reduce variability across practices treating women with epithelial ovarian cancer,” she said.
DISCLOSURE: For full disclosures of the study authors, visit jco.ascopubs.org.
1. Konstantinopoulos PA, Norquist B, Lacchetti C, et al: Germline and somatic tumor testing in epithelial ovarian cancer: ASCO Guideline. J Clin Oncol. January 27, 2020 (early release online).
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, January 29, 2020. All rights reserved.