Maintenance Therapy In Ovarian Cancer Research Articles

To Bev or Not to Bev during Ovarian Cancer Maintenance Therapy?

Maintenance therapy with PARP inhibitors and bevacizumab is approved for ovarian cancer treatment in the first and second line settings, but selecting the optimal sequence is challenging due to restrictions on using the same medication twice. This review aims to establish guidelines for ovarian cancer maintenance therapy based on the strength of scientific evidence, the most effective treatment strategy, and the impact on the healthcare system. Six questions were formulated to evaluate the scientific evidence supporting different maintenance therapy options using the AGREE II guideline evaluation tool. The questions address the acceptability of reusing the same medication, the efficacy of bevacizumab and PARP inhibitors in the first and second line settings, the comparative efficacy of these medications, the potential benefit of combination maintenance therapy, and the economic impact of maintenance therapy. Based on the available evidence, bevacizumab should be preserved for second line maintenance therapy, and maintenance therapy with PARP inhibitors should be offered to all advanced ovarian cancer patients who have responded to first line platinum-based chemotherapy. Additional molecular predictors for bevacizumab efficacy are needed. The presented guidelines offer an evidence-based framework for selecting the most effective maintenance therapy for ovarian cancer patients. Further research is necessary to refine these recommendations and improve outcomes for patients with this disease.

Abstract 4915: Sensitivity to NAMPT inhibition: In vitro and in vivo characterization in ovarian cancer

Abstract Previous in vitro work on determining the unique sensitivities of various cancers to nicotinamide phosphoribosyltransferase inhibitors (NAMPTis) has demonstrated promising effects of treating cancer cells with NAMPTis such as FK866 and KPT9274. These inhibitors act by disrupting cellular energy metabolism and reducing intracellular NAD+ levels. NAMPT inhibition thereby suppresses the proliferation of cancer cells which depend more heavily on the NAMPT enzyme to produce NAD+ than noncancerous cells. Using pan-cancer in vitro screens in a large panel of molecularly characterized cell lines (n = 496) we identified a subset of ovarian cancer, a cancer with a high unmet need due to lack of diverse targeted therapies, as being extremely sensitive to NAMPT inhibition. Subsequent in vivo work using CD-1 nude mice demonstrate that NAMPT inhibitors can successfully reduce the ovarian tumor burden and may be an effective treatment option of some ovarian cancers. Moreover, NAD+’s function as a substrate to the poly ADP-ribose polymerase (PARP) enzyme makes NAMPTis rational candidates for including in combination therapies with PARP inhibitors, several of which are approved for maintenance therapy for ovarian cancer. By using NAMPTis to disrupt the cellular metabolic process while simultaneously inhibiting PARP activity, an essential DNA damage repair enzyme, it is possible to exploit the dependence of ovarian cancer cells on functional PARP activity. This is particularly important in homologous recombination deficient subtypes. In addition to a synergistic growth inhibitory response in ovarian cancer cells, preclinical combination studies of NAMPTis with olaparib, an approved PARP inhibitor, exhibited higher levels of DNA damage accumulation than with single drug treatments. Our in vitro and in vivo characterizations of NAMPT inhibition suggest that NAMPTis as either single agents or in combination treatments with PARP inhibitors should be investigated further as potential treatment options for ovarian cancer patient populations. Citation Format: Jenny J. Hong, Martina S. McDermott, Neil A. O'Brien, Enrique Guandique, Tong Luo, Dennis J. Slamon. Sensitivity to NAMPT inhibition: In vitro and in vivo characterization in ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4915.

190P Real-world applications of poly (ADP-ribose) polymerase inhibitors for ovarian cancer: A single-center study in China

Olaparib and niraparib have been approved for first/second-line maintenance treatment of ovarian cancer patients in China for more than 3 years. In this study, we analyzed the clinical application characteristics of PARPi in the maintenance therapy of ovarian cancer in real world to promote their rational application.

570P Hypomethylating agents synergistically combine with PARP inhibitors in ovarian cancer

Poly (ADP-Ribose) polymerase inhibitors (PARPi’s) are currently used for first and second line maintenance therapy of ovarian cancer (OC) in patients whose tumors harbor defects in homologous recombination. Unfortunately, the rapid emergence of resistance leads to a short duration of response, and thus preventing PARPi resistance and extending the spectrum of patients who would benefit from PARP inhibition are urgent needs. While multiple drug classes have demonstrated synergy when combined with PARPi’s preclinically, head-to-head comparisons which would facilitate clinical prioritization of the most promising combinations are missing.

Shared decision making in frontline maintenance therapy for ovarian cancer: A qualitative assessment (590)

Shared decision making in frontline maintenance therapy for ovarian cancer: A qualitative assessment (590)

Conclusions: Race Matters: Disparities in the use of maintenance therapy in ovarian cancer (OC) (061)

Objectives: To determine the impact of race, insurance status, and median income on the uptake of maintenance therapy after primary or secondary chemotherapy in platinum responsive platinum-sensitive ovarian cancer (OC). Methods: This IRB-approved study evaluated the association of race, income, and insurance status with the use of maintenance therapy in the primary or platinum-sensitive recurrent setting. All patients were identified who were eligible for maintenance therapy from January 1, 2015, to December 31, 2019. Logistic regression models were used to investigate the association between the use of maintenance therapy and race, insurance status, and census tract median household income as determined by linking geocoded addresses to census data. Results: A total of 180 patients were identified who met the study criteria. Of these patients, 71 were treated with maintenance therapy (19% primary, 41% either). The most common treatments included PARPi in 46%, Bev in 41%, and both in 13%. Insurance status was commercial in 28%, public in 63%, and self-pay in 9%. The use of maintenance therapy was higher with commercial insurance than public or no insurance (26% vs 17% vs 12%), but this was not statistically significant (p=0.44). Patients receiving maintenance therapy lived in areas with slightly higher median household income, but this was not statistically significant ($71,828 vs $64,881; p=0.077). However, fewer black patients received maintenance therapy in either setting (20% vs 41%; p=0.034). Similarly, fewer Black patients received maintenance therapy in the primary setting (4% vs 21%: p = 0.040). In a multivariable regression model, race, census tract median income, and insurance status were not significantly associated with receiving maintenance therapy. Black patients were less likely to receive maintenance therapy in the multivariable model, although this did not reach significance (OR: 0.33; 95% CI: 0.10-1.08, p=0.08). Black patients are less likely to be treated with maintenance therapy after responding to platinum-based chemotherapy. This difference is not explained by insurance status or household income. It is important to understand why racial differences persist in healthcare delivery to optimize outcomes for all patients. Objectives: To determine the impact of race, insurance status, and median income on the uptake of maintenance therapy after primary or secondary chemotherapy in platinum responsive platinum-sensitive ovarian cancer (OC). Methods: This IRB-approved study evaluated the association of race, income, and insurance status with the use of maintenance therapy in the primary or platinum-sensitive recurrent setting. All patients were identified who were eligible for maintenance therapy from January 1, 2015, to December 31, 2019. Logistic regression models were used to investigate the association between the use of maintenance therapy and race, insurance status, and census tract median household income as determined by linking geocoded addresses to census data. Results: A total of 180 patients were identified who met the study criteria. Of these patients, 71 were treated with maintenance therapy (19% primary, 41% either). The most common treatments included PARPi in 46%, Bev in 41%, and both in 13%. Insurance status was commercial in 28%, public in 63%, and self-pay in 9%. The use of maintenance therapy was higher with commercial insurance than public or no insurance (26% vs 17% vs 12%), but this was not statistically significant (p=0.44). Patients receiving maintenance therapy lived in areas with slightly higher median household income, but this was not statistically significant ($71,828 vs $64,881; p=0.077). However, fewer black patients received maintenance therapy in either setting (20% vs 41%; p=0.034). Similarly, fewer Black patients received maintenance therapy in the primary setting (4% vs 21%: p = 0.040). In a multivariable regression model, race, census tract median income, and insurance status were not significantly associated with receiving maintenance therapy. Black patients were less likely to receive maintenance therapy in the multivariable model, although this did not reach significance (OR: 0.33; 95% CI: 0.10-1.08, p=0.08). Black patients are less likely to be treated with maintenance therapy after responding to platinum-based chemotherapy. This difference is not explained by insurance status or household income. It is important to understand why racial differences persist in healthcare delivery to optimize outcomes for all patients.

Frontline therapy of anlotinib combined with carboplatin/paclitaxel and maintenance anlotinib in patients with newly diagnosed advanced ovarian cancer: A phase II, single-arm, multicenter study.

TPS5607 Background: It has been reported that antiangiogenic drug combined with chemotherapy as first-line treatment, and subsequent antiangiogenic drug as maintenance therapy for ovarian cancer can achieve better clinical benefits. Anlotinib is a highly effective VEGFRs, FGFRs, PDGFRs and c-kit multi-target tyrosine kinase inhibitor which has been approved for the treatment of several solid tumors in China. This single arm, multicentric, phase II study is expected to investigate the efficacy and safety of anlotinib combined with carboplatin/paclitaxel as front-line treatment in patients with advanced ovarian cancer. Methods: Eligible patients with FIGO stage III–IV primary epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and ECOG PS 0-1 undergo primary debulking surgery or interval debulking surgery, will receive 6-8 cycles of chemotherapy (paclitaxel 175 mg/m2 + carboplatin area under the curve [AUC] 5 q3w) and anlotinib (12 mg po qd, days 1-14, 21 days per cycle, anlotinib will be omitted from the first treatment cycle to prevent delayed wound healing). Anlotinib as maintenance monotherapy will be continue until disease progression, unacceptable toxicity, or death. Patients with prior anti-angiogenic therapy and major surgical procedure within 28 days before the first date of anlotinib therapy will be excluded. This study will recruit approximately 56 patients. The primary endpoint is progression free survival. Key secondary endpoints include overall response rate, disease control rate per RECIST1.1, overall survival, safety. The study began enrolling patients in August 2021 and is ongoing. Clinical trial information: NCT04807166.

Safety Profile of Niraparib as Maintenance Therapy for Ovarian Cancer: A Systematic Review and Meta-Analysis.

Background: Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment. Objective: To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC. Methods: PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated. Results: A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, p < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, p = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, p < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, p = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, p < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, p < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, p < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, p = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, p = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, p < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, p < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, p = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials. Conclusion: Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.

Short-term starvation synergistically enhances cytotoxicity of Niraparib via Akt/mTOR signaling pathway in ovarian cancer therapy

BackgroundShort-term starvation (STS) has gradually been confirmed as a treatment method that synergistically enhances the effect of chemotherapy on malignant tumours. In clinical applications, there are still some limitations of poly (ADP-ribose) polymerase inhibitors (PARPi), including understanding their effectiveness and side effects. Here, we sought to investigate the effect and mechanism of the combined use of STS and niraparib in the treatment of ovarian cancer.MethodsIn in vitro experiments, SKOV3 and A2780 ovarian cancer cells were treated with STS and niraparib alone or in combination. Cell viability was assessed with CCK-8, and cell cycle, apoptosis, DNA damage repair and autophagy were examined to explore the molecular mechanisms. Akt and mTOR inhibitors were used to examine any changes in DNA damage repair levels. Xenograft animal models were treated with STS and niraparib, and HE staining and immunohistochemistry were performed to examine the effects.ResultsThe combined use of STS and niraparib inhibited cell proliferation and increased apoptosis more than niraparib application alone. In addition, compared with the niraparib group, the STS + niraparib group had increased G2/M arrest, DNA damage and autophagy, which indicated that STS pretreatment enhanced the cytotoxicity of niraparib. In animal experiments, STS did not affect the growth of transplanted tumours, but the combined treatment synergistically enhanced the cytotoxicity of niraparib. In in vivo experiments, STS did not affect the growth of transplanted tumours, but the combined treatment synergistically enhanced the cytotoxicity of niraparib and reduced the small intestinal side effects caused by niraparib chemotherapy.ConclusionSTS pretreatment can synergistically enhance the cytotoxicity of niraparib. STS + niraparib is a potentially effective strategy in the maintenance therapy of ovarian cancer.

Maintenance therapy for ovarian cancer at our institution

Maintenance therapy for ovarian cancer at our institution

Evaluation of patterns of progression on poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance in ovarian cancer: a cross-sectional study

IntroductionDespite improvement in progression-free survival with poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy for ovarian cancer, many patients will eventually progress on therapy. Oligoprogression is uniquely suited to considerations...

Update on Poly ADP-Ribose Polymerase Inhibitors in Ovarian Cancer With Non-BRCA Mutations.

Poly ADP-ribose polymerase inhibitor (PARPi) has become an important maintenance therapy for ovarian cancer after surgery and cytotoxic chemotherapy, which has changed the disease management model of ovarian cancer, greatly decreased the risk of recurrence, and made the prognosis of ovarian cancer better to certain extent. The three PARPis currently approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of ovarian cancer are Olaparib, Niraparib and Rucaparib. With the incremental results from new clinical trials, the applicable population of PARPi for ovarian cancer have expanded to population with non-BRCA mutations. Although BRCA mutated population are still the main beneficiaries of PARPi, recent clinical trials indicated PARPis’ therapeutic potential in non-BRCA mutated population, especially in homologous recombination repair deficiency (HRD) positive population. However, lack of unified HRD status detection method poses a challenge for the accurate selection of PARPi beneficiaries. The reversal of homologous recombination (HR) function during the treatment will not only cause resistance to PARPis, but also reduce the accuracy of the current method to determine HRD status. Therefore, the development of reliable HRD status detection methods to determine the beneficiary population, as well as rational combination treatment are warranted. This review mainly summarizes the latest clinical trial results and combination treatment of PARPis in ovarian cancer with non-BRCA mutations, and discusses the application prospects, including optimizing combination therapy against drug resistance, developing unified and accurate HRD status detection methods for patient selection and stratification. This review further poses an interesting topic: the efficacy and safety in patients retreated with PARPis after previous PARPi treatment---“PARPi after PARPi”.

Anti-Angiogenesis Maintenance Therapy in Newly Diagnosed and Relapsed Ovarian Cancer: A Meta-analysis of Phase III Randomized Controlled Trials.

Aim: Anti-angiogenesis agents have been added as maintenance therapy in ovarian cancer over the past decade. The aim of this meta-analysis was to analyze the efficacy of anti-angiogenesis therapy in newly diagnosed and relapsed ovarian cancer. Methods: PubMed, Embase, and Cochrane databases were searched for all phase III randomized controlled trials (RCTs) that assessed the efficacy and toxicity of anti-angiogenesis agents in ovarian cancer. Overall survival (OS) and progression-free survival (PFS) were used to evaluate the effectiveness of anti-angiogenesis therapy in ovarian cancer. Results: A total of 6097 patients with newly diagnosed ovarian cancer from 5 phase III RCTs and 2943 patients with relapsed ovarian cancer from 6 phase III RCTs were included in this meta-analysis. The pooled results showed that anti-angiogenesis maintenance therapy significantly improved PFS (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.76–0.93; p = 0.001), but not OS (HR, 0.98; 95% CI, 0.91–1.05; p = 0.49) compared with placebo in patients with newly diagnosed ovarian cancer. In patients with relapsed ovarian cancer, the pooled results showed a significant improvement on OS (HR, 0.89; 95% CI, 0.82–0.98; p = 0.02) and PFS (HR, 0.61; 95% CI, 0.52–0.72; p < 0.001). The pooled results also showed that the anti-angiogenesis agents were associated with an increase in the occurrence of severe hypertension, neutropenia, diarrhea, thrombocytopenia, headache, and bleeding in ovarian cancer. However, infrequent fatal adverse events occurred in the anti-angiogenesis groups. Conclusions: Study results suggest that anti-angiogenesis agents were an effective therapy for newly diagnosed and relapsed ovarian cancer, especially for relapsed ovarian cancer. Anti-angiogenesis agents may be associated with some severe but not fatal adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021283647

Real-world patterns and predictors of first-line maintenance use among patients with newly diagnosed advanced ovarian cancer: Is there an opportunity for change?

294 Background: With the advent of poly(ADP-ribose) polymerase inhibitors (PARPi), options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US. This study described the use of 1L maintenance and assessed predictors of 1L maintenance use among PARPi-eligible patients (pts) with OC in a real-world setting. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV epithelial OC who received 6–9 cycles of 1L platinum-based chemotherapy (PBC) and primary or interval debulking surgery following neoadjuvant chemotherapy between Jan 1, 2016, and Feb 29, 2020, from the nationwide Flatiron Health electronic health record–derived deidentified database. The end of the last cycle of 1L PBC was defined as the index date. Those pts who started second-line chemotherapy within 2 months of the index date were excluded. Logistic regression was used to analyze variables with regard to 1L maintenance use. Results: In total, 463 pts were included; 21% received maintenance therapy, 79% received active surveillance. Baseline characteristics are shown in the table. Overall maintenance therapy use increased over the study period, from 7.7% to 37.7%. Pts with BRCA wild type were significantly less likely to receive maintenance therapy (odds ratio [OR]: 0.30; 95% CI, 0.16–0.59) than pts with BRCA mutation. Pts treated in 2018 (OR: 2.73; 95% CI, 1.25–5.98) and 2019 (OR: 8.78; 95% CI, 4.15–18.55) were significantly more likely to receive maintenance therapy than pts treated in 2017. Age, race, practice type, ECOG score, and residual disease status were not significant predictors of 1L maintenance use. Conclusions: Nearly 40% of pts with advanced stage OC received upfront maintenance therapy with an increasing trend over time, particularly in those with biomarker guidance. Research is warranted toward addressing barriers to the appropriate use of maintenance therapy.[Table: see text]

"Efficacy of Letrozole as Maintenance Therapy for Ovarian Cancer"

"Efficacy of Letrozole as Maintenance Therapy for Ovarian Cancer"

Real-world progression-free survival among patients with newly diagnosed advanced ovarian cancer: Does maintenance therapy work?

e18707 Background: Options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US in recent years, particularly with FDA approvals of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi). Olaparib was approved in 2018 for 1L maintenance treatment of patients (pts) with advanced OC with BRCA mutation and in 2020 as combination therapy with bevacizumab for 1L maintenance treatment of pts with homologous recombination deficient (HRd)–positive tumors. Additionally, the FDA approved niraparib in 2020 for maintenance treatment of pts with advanced OC regardless of tumor biomarker status. This study aimed to describe use and outcomes of 1L maintenance vs. active surveillance (AS) among PARPi-eligible pts with OC in a real-world setting prior to the most recent 2020 FDA approvals. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV OC who received 6–9 cycles of 1L platinum-based chemotherapy (PBC) and either primary debulking surgery or interval debulking surgery following neoadjuvant chemotherapy between January 1, 2016, and February 29, 2020, regardless of biomarker status, from the Flatiron Health database, a longitudinal electronic health record-derived database consisting of de-identified patient-level data that are curated via technology-enabled abstraction. The end of the last cycle of 1L PBC was defined as the index date. Pts who started second-line (2L) treatment within 2 months of the index date were excluded. Primary endpoint was time to initiation of 2L systemic therapy (as a surrogate for progression) or death. Inverse probability of treatment weighting and Cox proportional hazard model were used to adjust for baseline differences among pts on maintenance therapy and pts on AS. Results: A total of 463 pts were included in the study, 87.7% from community practices and 12.3% from academic institutions. Of the pts included, 21.0% received maintenance therapy, while 79.0% did not. Of those who received maintenance therapy, 48.5% received bevacizumab, 40.2% received PARPi (olaparib, rucaparib), and 11.3% received paclitaxel. Median progression-free survival (PFS) for pts who received 1L maintenance therapy was 16.1 months, compared with 12.2 months in pts who did not receive 1L maintenance therapy. After adjusting for baseline differences in characteristics and demographics, including age, race, stage of cancer, and BRCA status, pts on maintenance therapy had a statistically significant, 29% lower risk of progression or death than those receiving AS (hazard ratio: 0.71; 95% CI, 0.52–0.99; P= 0.04). Conclusions: In this real-world analysis, the majority of pts did not receive maintenance therapy; however, a PFS benefit was found in those receiving maintenance therapy. Further studies are needed to understand how biomarker status drives practice patterns.

Real-world patterns and predictors of first-line maintenance use among patients with newly diagnosed advanced ovarian cancer: Is there an opportunity for change?

e18710 Background: With the advent of poly(ADP-ribose) polymerase inhibitors (PARPi), options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US. This study described the use of 1L maintenance and assessed predictors of 1L maintenance use among PARPi-eligible patients (pts) with OC in a real-world setting. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV epithelial OC who received 6–9 cycles of 1L platinum-based chemotherapy (PBC) and primary or interval debulking surgery following neoadjuvant chemotherapy between Jan 1, 2016, and Feb 29, 2020, from the nationwide Flatiron Health electronic health record–derived deidentified database. The end of the last cycle of 1L PBC was defined as the index date. Those pts who started second-line chemotherapy within 2 months of the index date were excluded. Logistic regression was used to analyze variables with regard to 1L maintenance use. Results: In total, 463 pts were included; 21% received maintenance therapy, 79% received active surveillance. Baseline characteristics are shown in the table. Overall maintenance therapy use increased over the study period, from 7.7% to 37.7%. Pts with BRCA wild type were significantly less likely to receive maintenance therapy (odds ratio [OR]: 0.30; 95% CI, 0.16–0.59) than pts with BRCA mutation. Pts treated in 2018 (OR: 2.73; 95% CI, 1.25–5.98) and 2019 (OR: 8.78; 95% CI, 4.15–18.55) were significantly more likely to receive maintenance therapy than pts treated in 2017. Age, race, practice type, ECOG score, and residual disease status were not significant predictors of 1L maintenance use. Conclusions: Nearly 40% of pts with advanced stage OC received upfront maintenance therapy with an increasing trend over time, particularly in those with biomarker guidance. Research is warranted toward addressing barriers to the appropriate use of maintenance therapy.[Table: see text]

The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials.

Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. Olaparib has been approved by the FDA for advanced ovarian and breast cancer with BRCA mutations, and as a maintenance therapy for ovarian cancer after platinum chemotherapy. PARPis are also a new and emerging clinical treatment for metastatic castration-resistant prostate cancer (mCRPC). Although PARPis have shown great efficacy, their widespread use is restricted by various factors, including drug resistance and the limited population who benefit from treatment. It is necessary to study the combination of PARPis and other therapeutic agents such as anti-hormone drugs, USP7 inhibitors, BET inhibitors, and immunotherapy. This article reviews the mechanism of PARP inhibition in the treatment of PC, the progress of clinical research, the mechanisms of drug resistance, and the strategies of combination treatments.

Using PARP Inhibitors in Frontline Maintenance Therapy for Ovarian Cancer.

Ovarian cancer is the leading cause of mortality among gynecologic cancers in the United States, expected to result in roughly 13,940 deaths in 2020. Between 2008 and 2017, mortality decreased by 2.3% per year. Incidence rates also decreased, with a 1.6% drop per year from 2007 to 2016. In 2020, an estimated 21,750 new cases of ovarian cancer will be diagnosed. The majority (90%) of ovarian cancers are epithelial ovarian cancer-often high-grade serous adenomas, which are associated with a poor prognosis and have the fewest known risk factors.

Patient preferences for side effects and decision-making factors associated with maintenance therapy for ovarian cancer

Objective: Women with ovarian cancer now have different options for maintenance therapy. Given the extended time over which maintenance therapy is given, we assessed patient preferences for potential side effects and decision-making factors.