The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer.

INTRODUCTION: Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management. METHODS: This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015. The frequency of inter-cycle delays >7 days was calculated using drug administration dates. Kaplan-Meier estimates were used to compare 2-year overall survival (OS) between patients who were delayed and those treated to schedule. Cox proportional hazards regression was used to investigate the impact of treatment delay on all-cause mortality. Inverse probability of treatment weighting propensity scores were used to adjust for confounding variables. RESULTS: Delays >7 days occurred in 35.3% of patients. Two-year OS probability was 62.7% in patients who experienced treatment delays >7 days (95% CI, 58.7-66.9) compared to 69.1% in those treated to schedule (95% CI, 66.2-72.0). Delays were not significantly associated with all-cause mortality when adjusted for confounders (HR 1.00 95% CI, 0.83-1.20, P = .9). CONCLUSIONS: Delays to chemotherapy treatment were not significantly associated with worsened survival in patients with advanced-stage ovarian cancer. These results can inform clinical decision making that prioritize toxicity management and quality of life for those treated with chemotherapy.

The impact of inter-cycle treatment delays on 5-year all-cause mortality in early-stage breast cancer: A retrospective cohort study.

BACKGROUND: Inter-cycle delays to chemotherapy are often required to manage drug toxicity. The impact of delays on mortality is poorly characterised. This retrospective cohort study examined the association of treatment delay with all-cause mortality in early-stage breast cancer. METHODS: This real-world analytical study included adult women with stage 2 or 3 breast cancer receiving first-line (neo-)adjuvant chemotherapy between 01/01/2014 and 31/12/2015 in England. Inter-cycle delays > 7 days during the treatment period were calculated, and the association of treatment delay with 5-year all-cause mortality was investigated. Survival was compared between patients experiencing treatment delay and those completing treatment to schedule using landmark methodology and Kaplan-Meier (KM) estimator. Cox proportional hazards regression was used to investigate the impact of delay on survival, using inverse probability of treatment weighting to adjust for confounding variables. RESULTS: 8567 patients were included. 17 % (1448) experienced inter-cycle delay > 7 days during the treatment period. 1120 (13 %) women had died at the end of the 5-year follow up period. Median follow-up time was 5.5 years. Survival probability was significantly lower in patients experiencing treatment delay by KM estimator analysis (p < 0.0001). Cox proportional hazards regression demonstrated a significant positive association between delay and 5-year all-cause mortality (HR 1.33 95 % CI 1.12-1.61, p < 0.001). CONCLUSIONS: This is the largest study of its kind demonstrating an association between treatment delay and all-cause mortality. These findings support interventions to improve toxicity management allowing completion of chemotherapy to schedule where patients experience treatment delay due to treatment-related toxicity or hospital capacity pressures.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Patient decision aids in mainstreaming genetic testing for women with ovarian cancer: A prospective cohort study.

OBJECTIVE: To evaluate patient preference for short (gist) or detailed/extensive decision aids (DA) for genetic testing at ovarian cancer (OC) diagnosis. DESIGN: Cohort study set within recruitment to the Systematic Genetic Testing for Personalised Ovarian Cancer Therapy (SIGNPOST) study (ISRCTN: 16988857). SETTING: North-East London Cancer Network (NELCN) population. POPULATION/SAMPLE: Women with high-grade non-mucinous epithelial OC. METHODS: A more detailed DA was developed using patient and stakeholder input following the principles/methodology of IPDAS (International Patients Decision Aids Standards). Unselected patients attending oncology clinics evaluated both a pre-existing short and a new long DA version and then underwent mainstreaming genetic testing by a cancer clinician. Appropriate inferential descriptive and regression analyses were undertaken. MAIN OUTCOME MEASURES: Satisfaction, readability, understanding, emotional well-being and preference for long/short DA. RESULTS: The mean age of patients was 66 years (interquartile range 11), and 85% were White British ethnicity. Of the participants, 74% found DAs helpful/useful in decision-making. Women reported higher levels of satisfaction (86% versus 58%, p < 0.001), right amount of information provided (76.79% versus49.12%, p < 0.001) and improved understanding (p < 0.001) with the long DA compared with the short DA. There was no statistically significant difference in emotional outcomes (feeling worried/concerned/reassured/upset) between 'short' and 'long' DA; 74% of patients preferred the long DA and 24% the short DA. Patients undergoing treatment (correlation coefficient (coef) = 0.603; 95% CI 0.165-1.041, p = 0.007), those with recurrence (coef = 0.493; 95% CI 0.065-0.92, p = 0.024) and older women (coef = 0.042; 95% CI 0.017-0.066, p = 0.001) preferred the short DA. Ethnicity did not affect outcomes or overall preference for long/short DA. CONCLUSIONS: A longer DA in OC patients has higher satisfaction without increasing emotional distress. Older women and those undergoing treatment/recurrence prefer less extensive information, whereas those in remission preferred a longer DA.

Seminoma and dysgerminoma: evidence for alignment of clinical trials and de-escalation of systemic chemotherapy.

Malignant germ cell tumours are a group of rare cancers whose incidence peaks in late adolescence and early adulthood. Dysgerminomas of the ovary and seminomas of the testis are analogous diseases, but seminomas have a 10-fold higher incidence. The two tumours are morphologically identical and are only differentiated by surrounding organ-specific tissue or testicular germ cell neoplasia in situ. They share genetic features including KIT and RAS mutations, amplification of chromosome 12p, and expression of pluripotency markers (NANOG (Nanog homeobox), OCT3/4 (Octamer-binding transcription factor 3/4), and SAL4 (Spalt-like trascription factor 4)). Both histologies are exquisitely sensitive to platinum chemotherapy, and the combination of bleomycin, etoposide, and cisplatin (BEP) yields survival rates greater than 90%. However, BEP causes significant, lifelong toxicity (cardiovascular, renal, respiratory, and neurological) in these young patients with an expectation of cure. Here, we comprehensively review the biological features of dysgerminoma and seminoma to demonstrate that they are biologically analogous diseases. We present available clinical trial data supporting de-escalation of chemotherapy treatment. Finally, we propose that future trials should enrol men, women, and children to benefit all patients regardless of age or sex.

The Landscape of Adoptive Cellular Therapies in Ovarian Cancer.

Ovarian cancers are typically poorly immunogenic and have demonstrated disappointing responses to immune checkpoint inhibitor (ICI) therapy. Adoptive cellular therapy (ACT) offers an alternative method of harnessing the immune system that has shown promise, especially with the success of chimeric antigen receptor T-cell (CAR-T) therapy in haematologic malignancies. So far, ACT has led to modest results in the treatment of solid organ malignancies. This review explores the possibility of ACT as an effective alternative or additional treatment to current standards of care in ovarian cancer. We will highlight the potential of ACTs, such as CAR-T, T-cell receptor therapy (TCR-T), tumour-infiltrating lymphocytes (TILs) and cell-based vaccines, whilst also discussing their challenges. We will present clinical studies for these approaches in the treatment of immunologically 'cold' ovarian cancer and consider the rationale for future research.

The role of PARP inhibitor combination therapy in ovarian cancer.

The use of PARP inhibitors (PARPi) has transformed the care of advanced high-grade serous/endometrioid ovarian cancer. PARPi are now available to patients in both the first-line and recurrent platinum-sensitive disease settings; therefore, most patients will receive PARPi at some point in their treatment pathway. The majority of this expanding population of patients eventually acquire resistance to PARPi, in addition to those with primary PARPi resistance. We discuss the rationale behind developing combination therapies, to work synergistically with PARPi and overcome mechanisms of resistance to restore drug sensitivity, and clinical evidence of their efficacy to date.

Disparity in the era of personalized medicine for epithelial ovarian cancer.

The treatment of high-grade serous ovarian cancer and high-grade endometrioid ovarian cancer has seen significant improvements in recent years, with BRCA1/2 and homologous recombination status guiding a personalized approach which has resulted in improved patient outcomes. However, for other epithelial ovarian cancer subtypes, first-line treatment remains unchanged from the platinum-paclitaxel trials of the early 2000s. In this review, we explore novel therapeutic approaches being adopted in the treatment of clear cell, mucinous, carcinosarcoma and low-grade serous ovarian cancer and the biological rational behind them. We discuss why such disparities exist, the challenges faced in conducting dedicated trials in these rarer histologies and look towards new approaches being adopted to overcome them.

Ovarian Cancer Therapy: Homologous Recombination Deficiency as a Predictive Biomarker of Response to PARP Inhibitors.

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have revolutionised the management of patients with high-grade serous and endometrioid ovarian cancer demonstrating significant improvements in progression-free survival. Whilst the greatest benefit is seen with BRCA1/2 mutant cancers, it is clear that the benefit extends beyond this group. This sensitivity is thought to be due to homologous recombination deficiency (HRD), which is present in up to 50% of the high-grade serous cancers. Several different HRD assays exist, which fall into one of three main categories: homologous recombination repair (HRR)-related gene analysis, genomic "scars" and/or mutational signatures, and real-time HRD functional assessment. We review the emerging data on HRD as a predictive biomarker for PARP inhibitors and discuss the merits and disadvantages of different HRD assays.

First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors.

BACKGROUND: OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949. METHODS: Phase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7-1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics. RESULTS: Eighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1-9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting >6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance proliferation or activation of T cells in peripheral blood or reduce circulating Tregs, and analyses of tumor biopsies did not demonstrate any consistent increase in effector T-cell infiltration or function, or decrease in infiltrating Tregs. CONCLUSION: No safety concerns were observed with INCAGN01949 monotherapy in patients with metastatic or advanced solid tumors. However, tumor responses and pharmacodynamic effects on T cells in peripheral blood and post-therapy tumor biopsies were limited. Studies evaluating INCAGN01949 in combination with other therapies are needed to further evaluate the potential of OX40 agonism as a therapeutic approach in patients with advanced solid tumors. TRIAL REGISTRATION NUMBER: NCT02923349.

PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies.

The use of PARP inhibitors (PARPi) in patients with epithelial ovarian cancer is expanding, with the transition from use in recurrent disease to the first-line setting. This is accompanied with an increasing population of patients who develop acquired PARPi resistance. Coupled with those patients with primary PARPi resistance, there is an urgent need to better understand mechanisms of resistance and identify means to overcome this resistance. Combination therapy offers the potential to overcome innate and acquired resistance, by either working synergistically with PARPi or by restoring homologous recombination deficiency, targeting the homologous recombination repair pathway through an alternate strategy. We discuss mechanisms of PARPi resistance and data on novel combinations which may restore PARPi sensitivity.

Poly(ADP-Ribose) Polymerase Inhibitor Combination Therapy.

ABSTRACT: The introduction of poly(ADP-ribose) polymerase (PARP) inhibitors has led to significant improvements in outcome for several cancer types, most notably high-grade serous ovarian cancer. However, in general, benefit is restricted to tumors characterized by either BRCA1/2 mutation or homologous recombination deficiency. Combination therapy offers the potential to overcome innate and acquired PARP inhibitor resistance by either working synergistically with PARP inhibitors or by targeting the homologous recombination repair pathway through an alternate strategy, to restore homologous recombination deficiency. Several biological agents have been studied in combination with PARP inhibitors, including inhibitors of vascular endothelial growth factor (vascular endothelial growth factor; bevacizumab, cediranib), AKT (capivasertib), PI3K inhibitors (buparlisib, alpelisib), epidermal growth factor receptor and BET inhibitors. In general, PARP inhibitor and biological agent combinations are well tolerated, and early data suggest that they are clinically effective in both BRCA1/2 mutant and wild-type cancers. In this review, we discuss multiple clinical trials that are underway examining the antitumor activity of the most promising combination strategies.

Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51-62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51-71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

PARP inhibitors and immunotherapy in ovarian and endometrial cancers.

Advanced ovarian and endometrial cancers have historically been associated with poor prognosis and few treatment options, limited to single or doublet chemotherapy regimens. The introduction of novel target therapies has transformed the management of these cancers. In contrast to chemotherapy, which inhibits DNA replication and mitosis, targeted therapies target cancer signalling pathways, stroma, immune-microenvironment and vasculature in tumour tissues. The most notable advances in gynaecological cancers have come from the introduction of PARP inhibitors and immune checkpoint inhibitors for ovarian and endometrial cancer, respectively. Several PARP inhibitors, which target defective DNA repair, have been approved as maintenance therapy for advanced ovarian cancer in both the first line and platinum-sensitive relapsed settings. Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have proven successful in advanced mismatch repair deficient endometrial cancers with use now being investigated beyond this population. This review will explore the biological rationale and clinical evidence behind the use of PARP inhibitors and immunotherapy in ovarian and endometrial cancers.

Targeting HPV in gynaecological cancers - Current status, ongoing challenges and future directions.

Despite the success of preventive vaccination, the Human Papilloma Virus still accounts for 266,000 deaths annually, as the main causative factor of cervical, vaginal, anal, penile and oropharyngeal cancers. Human Papilloma Virus infects epithelial cells, driving tumourigenesis primarily from incorporation of DNA into the host cellular genome. Translation of two particular Human Papilloma Virus-specific oncoproteins, E6 and E7, are the key drivers of malignancy. If diagnosed early cervical, vaginal and vulval cancers have good prognosis and are treated with curative intent. However, metastatic disease carries a poor prognosis, with first-line systemic treatment providing only modest increase in outcome. Having shown promise in other solid malignancies, immune checkpoint inhibition and therapeutic cancer vaccines have been directed towards Human Papilloma Virus-associated gynaecological cancers, mindful that persistent Human Papilloma Virus infection drives malignancy and is associated with immunosuppression and lack of T-cell immunity. In this review, we discuss novel therapeutic approaches for targeting Human Papilloma Virus-driven gynaecological malignancies including vaccination strategies, use of immunomodulation, immune checkpoint inhibitors and agents targeting Human Papilloma Virus-specific oncoproteins. We also highlight the evolving focus on exciting new treatments including adoptive T-cell therapies.

Role of Poly (ADP-Ribose) Polymerase inhibitors beyond BReast CAncer Gene-mutated ovarian tumours: definition of homologous recombination deficiency?

PURPOSE OF REVIEW: PARP inhibitors have transformed the management of BRCA mutant (BRCA) high-grade serous and endometroid ovarian cancer (HGOC). However, it is clear that the benefit can be extended beyond this subgroup, particularly to those cancers with homologous recombination repair deficiency (HRD). We review emerging molecular and clinical data to support the use of PARP inhibitors in HRD HGOC and discuss the advantages and disadvantages of different HRD assays. RECENT FINDINGS: Several phase 3 trials support the use of PARP inhibitor maintenance therapy beyond those patients with BRCA in the first-line and platinum-sensitive relapse setting. Many of these studies included HRD testing and it is clear, regardless of the assay used, that an incremental reduction in benefit is observed from BRCA tumours to HRD to homologous recombination proficient tumours. However, although currently available HRD assays predict the magnitude of benefit from PARP inhibitors, they consistently fail to identify a subgroup of patients who do not benefit. SUMMARY: Clinical data support the use of PARP inhibitor maintenance therapy beyond BRCA patients. Current HRD tests lack negative predictive value and more research is required to develop a composite HRD assay that provides a dynamic readout of HRD status.

Targeted therapies in gynaecological cancers.

The treatment of cancer has changed dramatically over the last decade, driven by increased understanding of the cancer genome, immune landscape, molecular alterations and aberrant pathways that drive cancer progression. Advances in molecular biology have led to the development of targeted agents, including monoclonal antibodies, small molecules and check-point inhibitors. Unlike chemotherapy, which inhibits DNA replication and mitosis, these agents target cancer signalling pathways, stroma, immune microenvironment and vasculature in tumour tissues. In gynaecological cancer, drugs targeting defective DNA repair, such as PARP inhibitors, have been approved for advanced ovarian cancer, and drugs targeting angiogenesis have been used in the treatment of advanced or recurrent ovarian and cervical cancers. Immune check-point inhibitors such as anti-PD-1/PD-L1 antibodies have proved successful for mismatch repair-deficient endometrial cancers and HPV-targeted therapies are under development for HPV-related malignancies. In this era of precision medicine, improved understanding of cancer biology and genomics needs to be utilised to develop predictive biomarkers for these targeted therapies to maximise patient benefit.

Body Mass Index and Outcomes in Germ-Cell Tumors.

INTRODUCTION: Obesity at the time of diagnosis has been associated with better outcomes in some metastatic cancers such as renal-cell cancer. The association between body mass index (BMI) and germ-cell tumor (GCT) outcomes has not been reported. We sought to assess the association between BMI and outcomes in men with GCT in a large hospital registry. PATIENTS AND METHODS: Electronic medical records for 1161 GCT patients treated at Dana-Farber Cancer Institute between 1997 and 2012 were reviewed. Information regarding BMI, histology, stage, treatment, and patient characteristics was obtained. We separately evaluated patients with clinical stage 1 and metastatic disease. Using logistic regression analysis, we investigated the association between BMI and clinical features, such as International Germ Cell Consensus Classification (IGCCC) and stage at diagnosis. We used Cox proportional hazards regression to assess the association between BMI and risk of relapse and GCT-specific death. RESULTS: Among men diagnosed with clinical stage 1 GCT, BMI ≥ 25 kg/m2 was not associated with an increased risk of relapse (hazard ratio = 0.83; 95% confidence interval, 0.53-1.30) compared to those with BMI < 25 kg/m2. In the metastatic disease setting, men with BMI < 25 kg/m2 were less likely to present with good-risk disease; however, BMI was not associated with risk of relapse (hazard ratio = 1.00; 95% confidence interval, 0.63-1.59, P = .99). CONCLUSION: There was no evidence for an association between BMI and GCT outcomes. A lower BMI was associated with adverse prognostic variables at presentation per IGCCC risk groups for metastatic GCT, but this was not associated with relapse.

Olaparib maintenance for first-line treatment of ovarian cancer: will SOLO1 reset the standard of care?

Maintenance therapy with PARP inhibitors has heralded a new era in the management of recurrent epithelial ovarian cancer. The greatest effect is seen in women with BRCA1/2 tumors but those without this mutation also benefit. However, in most patients, the drugs eventually fail to prevent progression, so alternative strategies are needed. The SOLO1 trial randomized women with BRCA1/2-mutated advanced ovarian cancer to olaparib or placebo maintenance after first-line chemotherapy. Olaparib significantly improved progression-free survival to a degree that has not been seen in other first-line trials in ovarian cancer. This landmark trial is likely to change practice for this group of women. Here, we focus on the SOLO1 results in the context of the current management of advanced ovarian cancer.