PARP inhibitors in the treatment of ovarian cancer: a review

Abstract

Purpose of review This article will review recent changes in the standard of care for olaparib, niraparib, and rucaparib, as well as ongoing trials evaluating this class of drugs in combination with antiangiogenic agents and PD-1/PD-L1 inhibitors. Recent findings Niraparib received FDA approval for use in patients with complete response or partial response to first-line platinum-based chemotherapy regardless of BRCAm or HRD status that was received in April 2020. FDA approval was received for olaparib in combination with bevacizamab for epithelial ovarian cancer patients with complete response/partial response to first-line chemotherapy and bevacizumab and g/sBRCA and/or genomic instability by Myriad myChoice CDx in May 2020. Summary In the last year, treatment with PARPi has extended to not only include BRCAm and HRD-deficient patients but also have shown improvement in outcomes in HRD-proficient patients. With these advancements, more patients can access these agents and receive benefit. In the upcoming years, it will be exciting to see the potential benefit when PARPs are added to other angiogenic antagonists and immunotherapy agents.

Germline Testing and Somatic Tumor Testing forBRCA1/2Pathogenic Variants in Ovarian Cancer: What Is the Optimal Sequence of Testing?

“… 40 Homologous recombination deficiency testing is becoming increasingly common in clinical care as it stratifies patients for maintenance therapy. 41 , 42 However, the intent of this analysis was to compare two different sequences of genetic testing in ovarian cancer, rather than a cost-effectiveness analysis of maintenance therapy options, which has already been published. 43 It is interesting to note that in the aforementioned cost-effectiveness analysis, olaparib must be less than $8,950 USD per month, or $107,400 USD per year, to be considered cost-effective at a willingness-to-pay threshold of $100,000 USD per PFLY.…”

Next-generation Sequencing-based Test for Resectable Colorectal Cancer in Real-world Clinical Practice

“…Indeed, the importance of the breast and ovarian cancer susceptibility proteins BRCA1 and BRCA2 has been well documented [35,36]. Genomic tests, such as Myriad myChoice® CDx (Myriad Genetics, Inc., Salt Lake City, UT, USA), which detects BRCA1 and BRCA2 mutants, have been approved by the FDA and are used to detect biomarkers for PARP inhibitor treatment [37]. Unfortunately, the relationship between CRC and HRD has not yet been fully studied.…”

Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer Part 2: Medical Perspectives

“…Notably, a vast majority of RCTs assessing PARPis as first and second lines that subsequently led to FDA/EMA approvals included patients who were platinum sensitive (evaluated through complete/partial response to platinum-based chemotherapy regimens), thus selecting specific populations that already exhibited a sensitivity profile close to PARPis [ 75 , 76 ].…”

“…In terms of frontline treatment, HRD (through MC-CDx) evaluation in PAOLA-1 patients appeared essential to guide treatment with olaparib plus bevacizumab, but niraparib exerted an effect irrespective of HRD status [ 52 , 76 , 77 ]. Interestingly, patients from the PRIMA trial were quite different from those from the PAOLA-1 trial, with more advanced cancer and less complete response.…”