BRCA-mutated Advanced Ovarian Cancer Research Articles

Real-world effectiveness of first-line maintenance olaparib in women with BRCA-mutated advanced ovarian cancer: U.S. retrospective cohort study.

5518 Background: Following cytoreductive surgery and first-line (1L) platinum based chemotherapy, 70% of patients (pts) with newly diagnosed advanced ovarian cancer (AOC) experience relapse within 3 years. 1L maintenance treatment (tx) with olaparib monotherapy, a poly (ADP-ribose) polymerase inhibitor, extended progression free survival in pts with BRCA mutated (BRCAm) AOC in the SOLO-1 (NCT01844986) randomized controlled trial (RCT). We aimed to describe real world characteristics, tx patterns, and clinical outcomes of pts with newly diagnosed, BRCAm AOC. Methods: Data were collected from 457 pts via electronic case report forms in the US. Pt eligibility criteria were positive BRCAm test result between Jan-June 2019 (6 months post 1L olaparib FDA approval), newly diagnosed AOC (no maintenance tx prior to index), aged ≥18 years, no RCT enrollment, no active neoplasia, no prior tx for metastatic/stage IV cancer. Pt follow up was until July 2021. Kaplan-Meier (KM) estimation was used for time to event analysis using progression proxies: Time to subsequent therapy and discontinuation (or death for both) from initiation of 1L maintenance olaparib monotherapy. Results: Pt mean age (±SD) at index was 62 (±10) years, 64% of pts were white and 18% African American; further clinical characteristics are in the table. 95% of pts received ≥1 pharmacological tx. At 1L, 36% of pts (156/433) received maintenance tx after chemotherapy, with 64% of pts (277/433) receiving routine surveillance (no maintenance tx). Olaparib was the most common maintenance tx (67%, 105/156), with 67% of pts (70/105) prescribed olaparib monotherapy. At 24 months, the KM model estimated 91% of pts (95% confidence interval: 82, 96) would not progress to their subsequent therapy, with a median discontinuation of olaparib monotherapy of 25.0 (interquartile range [IQR]: 21.0, not estimable) months, over a median follow-up of 22.0 (IQR: 20.6, 24.0) months. Conclusions: This real world study complements SOLO-1 RCT data by demonstrating prolonged benefit of 1L olaparib in newly diagnosed pts with BRCAm AOC in terms of lower likelihood of progression (tx switch/death). To assess real world tx effectiveness globally, data collection across further eight countries is due to be completed in 2022. [Table: see text]

Benefit of Olaparib for BRCA-Mutated Advanced Ovarian Cancer

Benefit of Olaparib for BRCA-Mutated Advanced Ovarian Cancer

DUETTE: A randomized phase II study to assess a second maintenance treatment with olaparib (ola) or ola+ceralasertib (cer), in patients (pts) with platinum-sensitive relapsed (PSR) epithelial ovarian cancer who have previously received PARP inhibitor maintenance treatment (NCT04239014).

TPS6104 Background: Ovarian cancer is the leading cause of death from gynecological cancers in the USA, and the fifth most common cause of cancer death in women. Ola is a PARPi approved for first-line maintenance treatment of BRCA-mutated advanced ovarian cancer in women who achieve a complete or partial response to platinum-based chemotherapy. Ola is also efficacious in combination with bevacizumab in the same population, independent of BRCA mutation status. Cer is a potent, oral, selective inhibitor of ATR. ATR is a critical DDR kinase that is activated in response to replication stress and stalled replication forks. There is no second maintenance standard of care for patients with PSR ovarian cancer who have previously received a PARPi in the maintenance setting. Pre-clinical models have shown that several mechanisms of PARPi resistance may be overcome by ATR inhibition, such as BRCA reversion, replication fork protection and DDR rewiring. DUETTE will select pts with tumor response or stable disease after second or third-line platinum-based treatment, with the expectation to enrich for non-BRCA reversion PARPi resistance mechanisms. The study will address the role of a second maintenance treatment following prior 1L or 2L maintenance, an emerging population of unmet need, and includes translational studies that aim to further our knowledge of clinical PARPi resistance mechanisms and predictors of treatment response. Methods: DUETTE is a global, multi-center, phase II study. 192 pts with PSR epithelial ovarian cancer who have previously received PARPi maintenance treatment, will be retreated with platinum and those who have not progressed after ≥ 4 cycles will be randomized (1:1:1) to 3 treatment arms: Arm 1, open-label: cer 160 mg once daily (qd) days 1 to 7 plus ola 300 mg twice daily (bd); Arm 2, blinded: ola monotherapy 300 mg bd and Arm 3, blinded: ola-placebo. Treatment is administered in 28-day cycles. All pts will be stratified by BRCA status (mutation or wildtype) and response to most recent line of platinum-based chemotherapy (CR/PR or SD). The primary endpoint is to assess the efficacy of maintenance ola monotherapy and cer+ola combination therapy compared with placebo by PFS using blinded, independent central review. Secondary endpoints are overall survival, PFS2, ORR, DoR, safety and tolerability. Enrolment is planned to start in April 2020.

225O - Impact of radiological disease progression on the health status of patients (pts) with BRCA-mutated advanced ovarian cancer (OC) treated with maintenance olaparib (OL) or placebo (PL) after first-line platinum chemotherapy

BackgroundIn SOLO1 (NCT01844986), maintenance OL significantly improved progression-free survival vs PL (HR 0.30; 95% CI 0.23–0.41; Moore et al. NEJM 2018) following response to first-line platinum chemotherapy in pts with BRCA-mutated advanced OC. We compared pt health status pre- and post-radiological progression (RECIST) in SOLO1 using the EQ-5D-5L descriptive system and visual analogue scale (VAS). MethodsEQ-5D-5L data were collected at baseline, day 29, every 12 weeks for 3 years, then every 24 weeks until data cut off (May 2018). Using the last EQ-5D-5L pre-progression as baseline, we assessed changes in each domain score, the proportion reporting any problem (levels 2–5) by domain, and Paretian classification of health change (PCHC) at first post-progression EQ-5D-5L. Impact of progression on VAS was assessed by mixed-effects repeated measures analysis. Data were pooled across study arms. Results74/100 OL pts and 81/95 PL pts with RECIST progression completed the EQ-5D-5L pre- and post-progression. Pre-progression, any problems were reported in 56%, 54%, 40%, 31% and 5% for anxiety/depression, pain/discomfort, usual activity, mobility, and self care respectively. Post-progression, proportions reporting problems with anxiety/ depression (68%), pain/discomfort (65%) and self care (15%) increased, while usual activity (43%) and mobility (30%) were unchanged. Across all levels, worsening was reported in anxiety/depression (34%), pain/discomfort (27%) and self care (13%). By PCHC, 56% reported worsening in at least one domain, with 37% reporting worse overall health status immediately post-progression. Progression was associated with a statistically significant and meaningful reduction in VAS (-0.0714, P < 0.0001). ConclusionsRadiological progression after response to first-line platinum chemotherapy is associated with worsening health status, with anxiety/depression and pain/discomfort most affected. These results highlight the impact of progression on pts and pt-reported health benefits of delaying progression with maintenance OL. Clinical trial identificationNCT01844986. Editorial acknowledgementMedical writing assistance was provided by Catherine Risebro, PhD, from Mudskipper Business Ltd, funded by AstraZeneca. Legal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureM.L. Friedlander: Honoraria (self), Honoraria (institution), Advisory / Consultancy: AstraZeneca; Non-remunerated activity/ies, Consulting: AbbVie; Research grant / Funding (institution): Beigene; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Takeda. R. Hettle: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. E. Parkhomenko: Honoraria (institution), Advisory / Consultancy, Full / Part-time employment, Employee of Parexel, which has received consultancy fees from AstraZeneca: AstraZeneca.

231P - Cost-effectiveness of olaparib vs routine surveillance in the maintenance setting for patients with BRCA-mutated advanced ovarian cancer after response to first-line platinum-based chemotherapy in Singapore

BackgroundIn the randomized, double-blind, phase 3 trial SOLO1, olaparib (OLA) in the maintenance setting demonstrated a 70% lower risk of disease progression or death than placebo in women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation. This study aimed to evaluate the cost-effectiveness of OLA maintenance therapy versus routine surveillance (RS) after response to first-line platinum-based chemotherapy in this population in Singapore. MethodsA three-state partitioned survival model was developed to simulate the lifetime (50 years) incremental cost-effectiveness ratio (ICER) of OLA versus RS from a healthcare payer perspective. Progression-free and overall survival curves were estimated using data from SOLO1 and extrapolated beyond the trial period using parametric survival models. Any patient who remained progression-free at year 7 was assumed to be a long-term survivor and no longer at risk of progression. Mortality rates for this group were modelled on all-cause mortality from the general population adjusted for BRCA1/2 mutation status. These assumptions were validated with local clinicians. Health state utilities and adverse event frequencies were obtained from SOLO1. Drug costs were sourced from local public healthcare institutions. Healthcare resource usage and costs were based on local clinician input and publications. A 3% discount rate was applied to costs and outcomes. Deterministic and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of results. ResultsThe base-case analysis of OLA maintenance therapy versus RS resulted in an ICER of SGD17,326 per quality-adjusted life year (QALY) gained. The ICER was most sensitive to variations in the discount rate and mortality risk in long-term survivors. PSA demonstrated that OLA was associated with an 81% probability of being cost-effective at a willingness-to-pay threshold of SGD50,000 per QALY gained. ConclusionsOLA has a high potential of being a cost-effective maintenance therapy versus RS for patients with BRCA1/2 mutated advanced ovarian cancer after response to first-line chemotherapy in Singapore. Legal entity responsible for the studyAstraZeneca Singapore Pte Ltd. FundingAstraZeneca Singapore Pte Ltd. DisclosureD.S. Tan: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD; Honoraria (self): Bayer; Honoraria (self): Genmab; Honoraria (self): Tessa Therapeutics; Honoraria (self): Merck Serono ; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche (Foundation Medicine); Research grant / Funding (self): National Medical Research Council Singapore Clinician Scientist Award; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Bayer; Advisory / Consultancy: ETC/D3 Singapore; Advisory / Consultancy: Tessa Therapeutics; Advisory / Consultancy: Genmab. J.J. Chan: Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Merck Sharp & Dohme; Advisory / Consultancy: Eisai; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): OncoQuest Inc; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Synthon; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Celgene. J.K. Loke: Full / Part-time employment: AstraZeneca. R. Hettle: Full / Part-time employment: AstraZeneca. C.C. Yu: Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.

Poly ADP ribose polymerase (PARP) for the treatment of BRCA-mutated advanced ovarian cancer

Abstract Standard therapy for patients with newly diagnosed advanced ovarian cancer consists of primary or interval debulking surgery and paclitaxel and carboplatin combination therapy (TC) including conventional TC therapy, dose dence TC therapy and TC with bevacizumab combination to maintenance therapy. The result of SOLO1 trial was reported as the median progression free survival (PFS) which was primary endpoint of SOLO1 for patients who received placebo was only 13.8 months while the median PFS for those who received olaparib which is first in class PARP inhibitor, being developed by AstraZeneca, was not reached but looks to be approximately three years longer than the placebo group [HR was 0.30; 95% CI: 0.23, 0.41; p From June 2019, we can use the therapy based on a companion diagnostic to select patients with deleterious or suspected deleterious germline BRCAmutation. And, we will be able to have the new treatment option, maintenance therapy with olaparib for BRCA mutated advanced ovarian cancer patients, in the near future.

BRCA1/2 somatic mutation detection in formalin-fixed paraffin embedded tissue by next-generation sequencing in Korean ovarian cancer patients

IntroductionThe detection of BRCA1/2 mutations is important because PARP1 inhibitors are approved for germline and/or somatic BRCA-mutated advanced ovarian cancer. Next-generation sequencing (NGS) is increasingly used in clinical practice for BRCA1/2 mutations. The purpose of this study was to consider several conditions of NGS BRCA1/2 assay applicable to clinical laboratory tests, in particular for using formalin fixed paraffin embedded (FFPE) ovarian tissues. Materials and methodsWe selected 64 ovarian cancer patients and performed Oncomine™ BRCA assay using FFPE tissue. Effect of FFPE sample quality was analyzed by NGS quality parameters including deamination metric. Somatic variants were selected by removing germline variants of peripheral blood and interpreted as pathogenic, variants of unknown significance, and false positive. ResultsWe found a positive relationship between the number of variants over the deamination metric and FFPE age (P < 0.001) with a cutoff values of approximately 0.7 and 60 months, respectively. When comparing NGS results with Sanger sequencing, NGS misreported 3 of 15 variants using default parameters which were corrected after changing parameters. We detected somatic variants in eight patients and classified them into pathogenic (n = 3), VUS (n = 3) and false positive (n = 2). ConclusionsThis study is important for improving BRCA1/2 mutation detection capabilities of NGS analytical pipelines and strategy to overcome their limitations using FFPE tissue in ovarian cancer patients.

FDA approves olaparib for first-line maintenance of BRCA-mutated advanced ovarian cancer

FDA approves olaparib for first-line maintenance of BRCA-mutated advanced ovarian cancer

Abstract PD6-11: An open-label, multitumor, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer (MBC)

Abstract Background Olaparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor, with first-in-class approval (400 mg capsules BID) for BRCA-mutated advanced ovarian cancer. Olaparib was recently found to be superior compared with chemotherapy in HER2-negative gBRCAm MBC in the Phase III OlympiAD trial. Olaparib induces DNA damage and genomic instability in gBRCAm tumors, which is hypothesized to result in enhanced immunogenicity. Here, we assess if a combination of olaparib and an anti-programmed cell death ligand-1 (PD-L1) agent, durvalumab, leads to enhanced antitumor activity in one of the four cohorts (NCT02734004). Methods Individuals with deleterious gBRCA1 or BRCA2 mutations and HER2-negative MBC were eligible. Patients with prior platinum therapy were allowed to enter if they had not experienced disease progression on platinum. No more than two prior lines of chemotherapy were allowed for metastatic disease, and patients with hormone receptor (HR) positive disease had to have at least one line of prior endocrine therapy. Concomitant use of endocrine therapy was not allowed. All patients received olaparib tablets 300 mg PO BID for a 4-week run-in, followed by a combination of olaparib 300 mg PO BID and durvalumab 1.5 g IV q 4 weeks. The combination was continued until progressive disease (PD) by RECIST 1.1 criteria. Tumor assessments were done at baseline, 4 weeks and every 8 weeks thereafter. The primary endpoint was disease control rate (DCR) at 12 weeks, and safety and tolerability of the combination. The secondary endpoints included DCR at 28 weeks, objective response rate, duration of response, progression-free survival (PFS) and overall survival. Biomarker endpoints included PD-L1 expression and evaluation of tumor infiltrating lymphocytes. Olaparib monotherapy has previously demonstrated a median PFS (mPFS) of 6 months in this patient population, and addition of durvalumab was predicted to increase the mPFS to 7.5 months, corresponding to a target DCR of 75% at 12 weeks. This was achievable by enrolling 30 patients using a Bayesian predictive probability design. Results of the first 25 patients are presented. Results Median age was 46 years (range 29−66); 11 and 14 patients had BRCA1 and BRCA2 mutations, respectively; 13 patients had HR positive disease, and nine had previously received platinum therapy. Median number of prior chemotherapy lines was 1 (range 0-4). Grade 3 or higher adverse events (AEs) were anemia (8%), neutropenia (8%), hemolysis (4%), dyspnea (4%), pancreatitis (4%), fatigue (4%), lymphopenia (4%) and leukopenia (4%). There was one grade 5 AE (dyspnea), which was attributed to disease progression. Observed DCR at 12 weeks was 80%. Eight confirmed responses and five unconfirmed responses were seen. The updated results from primary and secondary endpoints, including DCR at 28 weeks, as well as biomarker and PK data, will be presented. Conclusions The combination of olaparib and durvalumab was well tolerated, with no apparent overlapping toxicities. The efficacy of the combination at an early time point reached the target DCR in gBRCAm HER2-negative MBC, and warrants further investigation. Citation Format: Domchek SM, Postel-Vinay S, Bang Y-J, Park YH, Alexandre J, Delord J-P, Italiano A, You B, Bastian S, Krebs M, Wang D, Waqar S, Angell H, Learoyd M, Chang S-C, Gresty C, Herbolsheimer P, Kaufman B. An open-label, multitumor, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD6-11.

PARP inhibitors for targeted treatment in ovarian cancer

Poly(ADP-ribose) polymerase (PARP) inhibitors emerged as the first targeted treatment for ovarian cancer, and are selectively active for women with mutations in BRCA1 and BRCA2 (mBRCA). On the basis of data showing activity (measured by the proportion of patients who achieved an objective response), 1 Kim G Ison G McKee AE et al. FDA approval summary: olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy. Clin Cancer Res. 2015; 21: 4257-4261 Crossref PubMed Scopus (379) Google Scholar the PARP inhibitor olaparib received US Food and Drug Administration (FDA) approval in 2014 specifically for women with germline mBRCA-associated (gBRCA) recurrent ovarian cancer. 2 US Food and Drug AdministrationFDA approves Lynparza to treat advanced ovarian cancer. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427554.htm Google Scholar However, subsequent findings from clinical trials of PARP inhibitors have suggested that the importance of mBRCA as a predictive biomarker has diminished. For instance, among women without a germline mBRCA, predictors of PARP activity include a somatic (tumour) mutation in BRCA (sBRCA) and evidence of homologous recombination deficiency. 3 Swisher EM Lin KK Oza AM et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017; 18: 75-87 Summary Full Text Full Text PDF PubMed Scopus (785) Google Scholar , 4 Mirza MR Monk BJ Herrstedt J et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016; 375: 2154-2164 Crossref PubMed Scopus (1490) Google Scholar Indeed, FDA approval of the PARP inhibitor rucaparib in 2016 broadened the eligibility for PARP inhibitor treatment beyond gBRCA and included patients with sBRCA-associated ovarian cancers. 5 US Food and Drug AdministrationFDA grants accelerated approval to new treatment for advanced ovarian cancer. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm533873.htmDate: Dec 19, 2016 Google Scholar Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trialAcross all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Full-Text PDF

PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions.

Poly(ADP-ribose) polymerase (PARP) inhibitors cause targeted tumour cell death in homologous recombination (HR)-deficient cancers, including BRCA-mutated tumours, by exploiting synthetic lethality. PARP inhibitors are being evaluated in late-stage clinical trials of ovarian cancer (OC). Recently, olaparib was the first PARP inhibitor approved in the European Union and United States for the treatment of advanced BRCA-mutated OC. This paper reviews the role of BRCA mutations for tumorigenesis and PARP inhibitor sensitivity, and summarises the clinical development of PARP inhibitors for the treatment of patients diagnosed with OC. Among the five key PARP inhibitors currently in clinical development, olaparib has undergone the most extensive clinical investigation. PARP inhibitors have demonstrated durable antitumour activity in BRCA-mutated advanced OC as a single agent in the treatment and maintenance setting, particularly in platinum-sensitive disease. PARP inhibitors are well tolerated; however, further careful assessment of moderate and late-onset toxicity is mandatory in the maintenance and adjuvant setting, respectively. PARP inhibitors are also being evaluated in combination with chemotherapeutic and novel targeted agents to potentiate antitumour activities. Current research is extending the use of PARP inhibitors beyond BRCA mutations to other sensitising molecular defects that result in HR-deficient cancer, and is defining an HR-deficiency signature. Trials are underway to determine whether such a signature will predict sensitivity to PARP inhibitors in women with sporadic OC.

Olaparib for the treatment of BRCA-mutated advanced ovarian cancer.

The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of olaparib, a first-in-class treatment for advanced treatment-refractory ovarian cancer, are reviewed. Olaparib (Lynparza, AstraZeneca) is an oral inhibitor of poly(ADP-ribose) polymerase (PARP) proteins that play a key role in DNA repair and genomic stability. Olaparib is indicated for use in treating certain patients with advanced, recurrent ovarian cancer who have mutations of the breast cancer 1 gene (BRCA1) or breast cancer 2 gene (BRCA2). In patients with BRCA-mutated cancers, olaparib blocks vital PARP-mediated tumor cell DNA repair mechanisms, leading to "synthetic lethality" and selective tumor cell death. In Phase II clinical trials including patients with platinum-sensitive, platinum-resistant, and platinum-refractory ovarian cancers, olaparib significantly improved progression-free survival, with similar rates of response reported in patients with BRCA1- and BRCA2-mutated disease. Olaparib is generally well tolerated; the most commonly reported adverse events in clinical trials were mild nausea, fatigue, vomiting, and diarrhea. Severe anemia and severe fatigue can occur in association with olaparib treatment. Concurrent administration of olaparib and strong or moderate inducers or inhibitors of cytochrome P-450 isozyme 3A should be avoided, as use of those agents may alter plasma concentrations of olaparib. Olaparib is a novel PARP inhibitor that is efficacious and well tolerated in patients with BRCA-mutated advanced ovarian cancers who have received three or more lines of prior treatment.

Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy.

Rucaparib camsylate (CO-338; 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt) is a PARP1, 2 and 3 inhibitor. Phase I studies identified a recommended Phase II dose of 600 mg orally twice daily. ARIEL2 Part 1 established a tumor genomic profiling test for homologous recombination loss of heterozygosity quantification using a next-generation sequencing companion diagnostic (CDx). Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy. Comparable to rucaparib development, other PARP inhibitors, such as olaparib, niraparib, veliparib and talazoparib, are developing CDx tests for targeted therapy. PARP inhibitor clinical trials and CDx assays are discussed in this review, as are potential PARP inhibitor combination therapies and likely resistance mechanisms.

Olaparib for BRCA-mutated advanced ovarian cancer

Olaparib for BRCA-mutated advanced ovarian cancer