PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline

Abstract

PURPOSE To provide recommendations on the use of poly(ADP-ribose) polymerase inhibitors (PARPis) for management of epithelial ovarian, tubal, or primary peritoneal cancer (EOC). METHODS Randomized, controlled, and open-labeled trials published from 2011 through 2020 were identified in a literature search. Guideline recommendations were based on the review of the evidence, US Food and Drug Administration approvals, and consensus when evidence was lacking. RESULTS The systematic review identified 17 eligible trials. RECOMMENDATIONS The guideline pertains to patients who are PARPi naïve. All patients with newly diagnosed, stage III-IV EOC whose disease is in complete or partial response to first-line, platinum-based chemotherapy with high-grade serous or endometrioid EOC should be offered PARPi maintenance therapy with niraparib. For patients with germline or somatic pathogenic or likely pathogenic variants in BRCA1 (g/s BRCA1) or BRCA2 (g/s BRCA2) genes should be treated with olaparib. The addition of olaparib to bevacizumab may be offered to patients with stage III-IV EOC with g/s BRCA1/2 and/or genomic instability and a partial or complete response to chemotherapy plus bevacizumab combination. Maintenance therapy (second line or more) with single-agent PARPi may be offered for patients with EOC who have not received a PARPi and have responded to platinum-based therapy regardless of BRCA mutation status. Treatment with a PARPi should be offered to patients with recurrent EOC that has not recurred within 6 months of platinum-based therapy, who have not received a PARPi and have a g/s BRCA1/2, or whose tumor demonstrates genomic instability. PARPis are not recommended for use in combination with chemotherapy, other targeted agents, or immune-oncology agents in the recurrent setting outside the context of a clinical trial. Recommendations for managing specific adverse events are presented. Data to support reuse of PARPis in any setting are needed. Additional information is available at www.asco.org/gynecologic-cancer-guidelines .

Targeting Myeloid-Derived Suppressor Cells in Ovarian Cancer

“…Interestingly, two recent reports have suggested an association between decreased MDSCs and favorable treatment outcomes in ovarian cancer patients. Lee et al showed that germline BRCA1 and 2 mutation-associated ovarian cancer, which is believed to have higher response rates to platinum-based chemotherapy than BRCA wild-type [34], has fewer circulating MDSCs and higher CD8 + T cells in PBMC compared with BRCA wildtype ovarian cancer [24]. Second, Li et al demonstrated that metformin treatment in diabetic patients with ovarian cancer was associated with reduced circulating MDSCs, a concomitant increase in the circulating CD8 + T cells, and longer survival [29].…”

The Role of PARP Inhibitors in the Ovarian Cancer Microenvironment: Moving Forward From Synthetic Lethality

“…Currently, PARPi have been implemented in the clinical standards as maintenance therapy in first line BRCA mutated high grade serous ovarian cancer (HGSOC) stages III and IV after partial or complete response to platinum salts, in II line and onward for platinum sensitive relapsed high grade serous or endometrioid OC (4).…”

Liquid Biopsy in the Clinical Management of High-Grade Serous Epithelial Ovarian Cancer—Current Use and Future Opportunities

“…For example, due to early pathogenic mutations in the TP53 gene, the tumor genome is largely unstable with a progressive increase in different kinds of structural aberrations. In this scenario, biological information provided by the single primary tumor biopsy at diagnosis, when the tumor is naive to chemotherapy, does not allow us to identify those sub-clonal molecular alterations, e.g., reversion of somatic BRCA mutations, which may have been developed in the metachronous lesions, thus characterizing the genome of relapsed disease and its resistance to conventional drugs [30][31][32].…”