Targeted Oncology最新文献

{"title":"Role of immunotherapy in early breast cancer: past, present, and future.","authors":"Karissa Britten, Aditya Bardia, Nicholas McAndrew","doi":"10.1007/s11523-025-01157-1","DOIUrl":"10.1007/s11523-025-01157-1","url":null,"abstract":"<p><p>The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment over the last decade, starting with the US Food and Drug Administration (FDA) approval of ipilimumab in 2011. Since that time, the FDA has approved nine additional ICIs, which now serve as frontline agents in lung, colorectal, head and neck, genitourinary, and skin cancers. ICIs have been practice-changing across many cancer subtypes, and their role in breast cancer (particularly in early-stage disease) is a topic of ongoing research. The only current FDA-approved ICI indication in early breast cancer is for the use of pembrolizumab in high-risk, triple-negative breast cancer in combination with chemotherapy, based on results from the KEYNOTE-522 trial. Although numerous trials have further investigated the use of ICIs in early-stage triple-negative breast cancer, survival outcomes have been inconsistent. Studies investigating the use of ICIs in early-stage estrogen receptor-positive and human epidermal growth factor receptor 2-positive breast cancer are even more limited, although available data (especially for estrogen receptor-positive disease) are promising. Numerous studies are ongoing, including critical investigations into biomarkers that may help determine which patients with breast cancer are most likely to benefit from the addition of immunotherapy. In this review, we discuss the history of ICI development, key trials investigating the use of ICIs in early-stage breast cancer, and future directions in the field.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"615-625"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Anti-GD2 Immunotherapy with Dinutuximab Beta in the Treatment of Relapsed/Refractory High-Risk Neuroblastoma.","authors":"Aleksandra Wieczorek, Katarzyna Śladowska, Holger N Lode","doi":"10.1007/s11523-025-01155-3","DOIUrl":"10.1007/s11523-025-01155-3","url":null,"abstract":"<p><strong>Background: </strong>High-risk neuroblastoma (HR-NB) is associated with a poor prognosis. Standard first-line maintenance therapy with anti-disialoganglioside 2 (GD2) monoclonal antibodies, such as dinutuximab beta, has improved survival rates; however, approximately 50% of patients experience relapse and ~15% have disease that is refractory to induction therapy.</p><p><strong>Objective: </strong>This systematic literature review aimed to evaluate response rates, survival outcomes, and safety in patients with relapsed or refractory (R/R) HR-NB receiving dinutuximab beta as maintenance therapy.</p><p><strong>Patients and methods: </strong>We searched the PubMed, Embase, and Cochrane Library databases and regulatory reports from inception to 1 September 2024, and included studies of patients with R/R HR-NB in which dinutuximab beta (± isotretinoin) was used as maintenance therapy and that reported objective response or survival rates. Studies of dinutuximab beta plus chemotherapy combinations were excluded.</p><p><strong>Results: </strong>We included nine publications/reports representing seven studies and 442 patients receiving dinutuximab beta. Across studies, the mean age was 5.1-6.4 years, and most patients were male. Reporting of response varied across studies between best response and end-of-treatment response. Best response rates with dinutuximab beta were 28.6-54.8%. All studies reported overall survival (OS), but follow-up times varied. Where reported, 3-year OS rates for patients receiving dinutuximab beta were 54-86% overall, with better OS rates reported for refractory than relapsed patients. Adverse events were frequent but manageable.</p><p><strong>Conclusions: </strong>Maintenance therapy for patients with R/R HR-NB with dinutuximab beta as monotherapy or in combination with isotretinoin demonstrated efficacy and acceptable safety. Further studies are needed in patients previously treated with anti-GD2 therapies to evaluate efficacy and impact on target antigens.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"551-568"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Podcast on Integrating Genetic Testing for Homologous Recombination Repair Gene Alterations in Patients with Prostate Cancer in the USA: a Multidisciplinary Approach to Overcoming the Obstacles.","authors":"Brittany M Szymaniak, Alicia K Morgans, Neal D Shore","doi":"10.1007/s11523-025-01159-z","DOIUrl":"10.1007/s11523-025-01159-z","url":null,"abstract":"<p><p>Homologous recombination repair (HRR) gene alterations in prostate cancer predispose patients to more aggressive disease and a poorer prognosis. The presence of these HRR gene alterations may inform patient eligibility for clinical trials and targeted therapies, and importantly, through cascade testing, help identify family members at risk of developing an inherited cancer. This finding highlights the importance of testing for HRR gene alterations in patients with prostate cancer. Despite the potential implications of such testing to patient care, in a cross-sectional retrospective study in the USA, only 37.7% of patients with advanced prostate cancer underwent HRR testing between 2014 and 2022. The aim of this podcast is to identify obstacles to testing for HRR gene alterations that healthcare professionals encounter in day-to-day clinical practice, as well as discuss ways to potentially overcome them. In this multidisciplinary podcast, a genetic counselor, a medical oncologist, and a urologist discuss the importance of testing for HRR gene alterations and, using their different clinical perspectives, explore ways that healthcare professionals can integrate testing results into clinical practice.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"543-550"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effectiveness of Atezolizumab Plus Bevacizumab Versus Tremelimumab Plus Durvalumab in Patients with Hepatocellular Carcinoma (HCC) in a Real-World Setting.","authors":"Federica Lo Prinzi, Federico Rossari, Marianna Silletta, Silvia Camera, Silvia Foti, Mara Persano, Francesco Vitiello, Emanuela Di Giacomo, Mariam Grazia Polito, Margherita Rimini, Andrea Casadei-Gardini","doi":"10.1007/s11523-025-01161-5","DOIUrl":"10.1007/s11523-025-01161-5","url":null,"abstract":"<p><strong>Background: </strong>There are no studies that directly compare atezolizumab plus bevacizumab and tremelimumab plus durvalumab (STRIDE), two first-line options for the systemic therapy of advanced hepatocarcinoma (HCC).</p><p><strong>Objective: </strong>We conducted a real-world retrospective analysis to compare the clinical efficacies of these two regimens.</p><p><strong>Patients and methods: </strong>Using TriNetX data on patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stages B or C, the analysis included patients treated with atezolizumab plus bevacizumab or with the STRIDE regimen. The primary endpoint was overall survival (OS) comparing the two treatment groups.</p><p><strong>Results: </strong>Before applying propensity-score matching, a total of 2,307 consecutive patients were identified. Among them, 1,998 received atezolizumab plus bevacizumab, and 309 were treated with STRIDE. After matching, 618 patients remained, with 309 in each cohort. The analysis showed no significant difference between the two treatments: median OS was 15.4 months (95% confidence interval (CI) 14.7-51.6) and 15.5 months (95% CI 15.0-47.0) for patients treated with atezolizumab plus bevacizumab versus STRIDE, respectively (HR 0.94; 95% CI 0.73-1.22, p = 0.67). The univariate analyses of baseline clinical and laboratory characteristics indicated that the only differentiating factor between the two regimens was better survival for females receiving atezolizumab plus bevacizumab (HR 1.77; 95% CI 1.00-3.16, p = 0.04).</p><p><strong>Conclusions: </strong>Atezolizumab plus bevacizumab and STRIDE demonstrated no statistical difference in OS, showing them to be equally valid alternatives for patients with advanced HCC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"707-713"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Streamlining and Accelerating the Molecular Tumor Board Process at the University Medical Center Hamburg-Eppendorf.","authors":"Layla Tabea Riemann, Maximilian Ataian, Felicia P S Hähner, Benjamin Roth, Alexander Knurr, Anne Kamitz, Maximilian Christopeit, Carsten Bokemeyer, Frank Ückert","doi":"10.1007/s11523-025-01160-6","DOIUrl":"10.1007/s11523-025-01160-6","url":null,"abstract":"<p><strong>Background: </strong>We developed, introduced, and evaluated Molecular ONcology Optimized CLinical Evaluation (MONOCLE), a secure, open-source web application at the University Medical Center Hamburg-Eppendorf (UKE), to optimize the analysis and discussion of complex cancer cases in molecular tumor boards (MTB).</p><p><strong>Objective: </strong>MONOCLE standardizes and harmonizes documentation, while its integrated Knowledge Connector accelerates literature research for personalized treatment.</p><p><strong>Patients and methods: </strong>The system was designed by merging the requirements of the German Network for Personalized Medicine (DNPM), the medical staff involved in the MTB process, and the team developing MONOCLE. The usability was evaluated using the System Usability Scale (SUS) and user tasks. Overall process optimization was measured by the number of automated tasks that can be performed.</p><p><strong>Results: </strong>MONOCLE, introduced into clinical practice in June 2024, significantly reduces time for documentation, as three manual steps now run automatically, and transfer of the data to the DNPM is possible. Its usability and SUS showed positive results, ranging between 92.5 and 97.5.</p><p><strong>Conclusions: </strong>As the first open-source and extendable solution for standardized MTB documentation, MONOCLE enables wider adoption by other medical centers.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"725-735"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase I Study of the Anti-CEACAM6 Antibody Tinurilimab (BAY 1834942) in Patients with Advanced Solid Tumors.","authors":"Lillian L Siu, David S Hong, Wolf-Dietrich Döcke, Reimo Tetzner, Mark Trautwein, Charles Phelps, Joerg Willuda, Xiang Qing Yu, Hendrik Nogai, Melissa Johnson, Boon Cher Goh","doi":"10.1007/s11523-025-01154-4","DOIUrl":"10.1007/s11523-025-01154-4","url":null,"abstract":"<p><strong>Background: </strong>Tinurilimab is a humanized immunoglobulin G subclass 2 antibody that blocks carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), an immune checkpoint regulator that is overexpressed in several tumor types.</p><p><strong>Objectives: </strong>This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and tumor response profile of tinurilimab in patients with advanced solid tumors with a described expression of CEACAM6.</p><p><strong>Patients and methods: </strong>In this first-in-human, dose-escalation and dose-expansion study, tinurilimab was administered as a 1-h intravenous infusion in 21-day cycles at a starting dose of 2.5 mg, with a planned escalation up to 1800 mg. Following observation of treatment toxicity (cytokine release syndrome in one patient and neutropenia in all patients treated at 30 mg), a premedication regimen was initiated that included dexamethasone 8 mg before and after dosing. Thirty patients received treatment across six dosing cohorts (2.5-100 mg with or without dexamethasone).</p><p><strong>Results: </strong>The maximum tolerated dose was not determined, as the study was terminated due to an unfavorable benefit/risk assessment. All 30 patients (100%) treated with tinurilimab experienced at least one treatment-emergent adverse event of any grade, most commonly fatigue (36.7%), infusion-related reaction (30.0%), and neutropenia (26.7%). The most common grade ≥ 3 treatment-related adverse events were neutropenia (23.3%), followed by febrile neutropenia, cytokine release syndrome, increased hepatic enzymes, decreased lymphocyte count, hypophosphatemia, lactic acidosis, and acute kidney injury (3.3% each). No patients reported an objective response.</p><p><strong>Conclusions: </strong>Following study termination, the clinical development program for tinurilimab was discontinued permanently.</p><p><strong>Clinical trial registration: </strong>www.</p><p><strong>Clinicaltrials: </strong>gov , NCT03596372.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"637-649"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relugolix in Combination with Androgen Receptor Pathway Inhibitors in the Treatment of Metastatic Prostate Cancer: A Clinical Perspective.","authors":"Tomas Buchler","doi":"10.1007/s11523-025-01150-8","DOIUrl":"10.1007/s11523-025-01150-8","url":null,"abstract":"<p><p>Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, has been established as an effective androgen deprivation therapy (ADT) for advanced prostate cancer, offering advantages over traditional GnRH agonists. The combination of relugolix with androgen receptor pathway inhibitors (ARPIs) is increasingly utilized in clinical practice, necessitating an understanding of its pharmacokinetics, efficacy, safety, and drug-drug interactions. This review explores the real-world data and clinical studies evaluating relugolix coadministration with ARPIs, including enzalutamide, abiraterone, apalutamide, and darolutamide. Pharmacokinetic interactions, particularly via the CYP3A4 enzyme system and P-glycoprotein (P-gp) transporter, influence drug exposure and, in theory, necessitate dose adjustments in certain combinations. However, clinical studies and real-world studies suggest that relugolix maintains testosterone suppression when combined with ARPIs even if administered in a standard dose. While these findings support the efficacy and safety of relugolix-based combination therapy, further large-scale prospective trials are needed to refine treatment recommendations and provide information on long-term outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"627-635"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Tolerability of Relugolix in Combination with Abiraterone or Apalutamide for Treatment of Patients with Advanced Prostate Cancer: Data from a 52-Week Clinical Trial.","authors":"Jose De La Cerda, Laurence Belkoff, Kevin D Courtney, Elan Diamond, James D'Olimpio, Curtis Dunshee, Lawrence Gervasi, Michael Goodman, Kriti Mittal, David Morris, Paul Sieber, Ronald Tutrone, Michael Ryan, Yi Zhong, Mike Ufer, Neal Shore","doi":"10.1007/s11523-025-01139-3","DOIUrl":"10.1007/s11523-025-01139-3","url":null,"abstract":"<p><strong>Background: </strong>The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix is the only oral androgen deprivation therapy (ADT) indicated for advanced prostate cancer (aPC). Combining ADT with androgen receptor signaling inhibitors (ARSIs) has shown improved clinical outcomes.</p><p><strong>Objective: </strong>To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of relugolix in combination with ARSIs in patients with aPC.</p><p><strong>Methods: </strong>In this 52-week, open-label study, patients received relugolix (120 mg once daily) with abiraterone (1,000 mg once daily) and corticosteroid (Part 1) or relugolix (240 mg once daily) with apalutamide (240 mg once daily) (Part 2). Metastatic castration-sensitive patients were eligible for both parts, whereas castration-resistant patients were eligible for Part 1 if metastatic and Part 2 if non-metastatic. Adverse events and other safety data were evaluated over 52 weeks, while pharmacodynamic and pharmacokinetic (Part 2 only) data were assessed over 12 weeks. Medication adherence to relugolix was measured by pill count.</p><p><strong>Results: </strong>Of 48 patients, 21 completed Part 1 and 20 completed Part 2. Most adverse events were grade 1 or 2, with hypertension (Part 1) and rash (Part 2) being most common. Mean testosterone concentrations remained below castrate level. Median prostate-specific antigen concentration was 0.04 ng/mL at week 12 in both parts. Concentrations of relugolix, apalutamide, and N-desmethyl-apalutamide were stable over 12 weeks similar to previous data. Relugolix adherence rates were > 97% in both parts.</p><p><strong>Conclusions: </strong>The safety/tolerability profile of both combination therapies was consistent with those of the individual drugs. These findings support using relugolix in combination with abiraterone or apalutamide as treatment of aPC.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT04666129.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"503-517"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor Degraders for Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.","authors":"Erika P Hamilton, Rinath M Jeselsohn, Linda T Vahdat, Sara A Hurvitz","doi":"10.1007/s11523-025-01137-5","DOIUrl":"10.1007/s11523-025-01137-5","url":null,"abstract":"<p><p>The estrogen receptor (ER) signaling pathway is a key driver of breast cancer, primarily through the activation of genes that promote tumor cell survival and growth. The recommended first-line treatment for ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer is endocrine therapy plus a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. However, most patients experience disease progression, and there is no clear standard of care in the second-line setting. Thus, novel treatments in the advanced setting are needed. In this narrative review, we describe the unique mechanisms of action of a new class of drugs called PROteolysis TArgeting Chimera (PROTAC) ER degraders. Unlike other ER-targeted therapies, these small molecules harness the body's primary intracellular natural protein disposal machinery, the ubiquitin-proteasome system, to directly induce ER degradation. Vepdegestrant (ARV-471) is the furthest advanced PROTAC ER degrader currently in clinical development. Preclinical data demonstrate increased tumor growth inhibition with vepdegestrant alone or in combination with CDK4/6 inhibitors compared with the selective ER degrader fulvestrant. In a first-in-human phase 1/2 clinical study, vepdegestrant administered orally as monotherapy or in combination with palbociclib showed promising clinical activity and a favorable safety profile in patients with heavily pretreated ER+/HER2- advanced breast cancer. Several other PROTAC ER degraders (AC699, ERD-3111, ERD-4001, and HP568) are in early development and have demonstrated activity in preclinical breast cancer models, with some recently entering clinical trials. The data highlight the potential for PROTAC ER degraders to be a new backbone therapy in breast cancer.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"431-444"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olaparib Monotherapy or in Combination with Abiraterone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) and a BRCA Mutation.","authors":"Fred Saad, Andrew J Armstrong, Neal Shore, Daniel J George, Mototsugu Oya, Mikio Sugimoto, Rana R McKay, Maha Hussain, Noel W Clarke","doi":"10.1007/s11523-025-01146-4","DOIUrl":"10.1007/s11523-025-01146-4","url":null,"abstract":"<p><p>Treatment strategies to improve outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) are evolving. Of particular interest are therapies that target DNA damage responses in tumor cells by inhibiting poly(ADP-ribose) polymerase (PARP) activity. Several PARP inhibitors have recently received regulatory approval for the treatment of patients with mCRPC, of which olaparib was the first for prostate cancer. Olaparib received approval as a monotherapy following the PROfound study (NCT02987543) and in combination with abiraterone following the PROpel study (NCT03732820) for mCRPC. Both PROfound (homologous recombination repair mutation biomarker-selected) and PROpel (biomarker unselected) patients demonstrated statistically significant longer radiographic progression-free survival (rPFS) with olaparib versus their respective control arms in the intention-to-treat population. In both studies, the greatest clinical benefit with olaparib was seen in patients with BRCA1 and/or BRCA2 mutations (BRCAm): PROfound rPFS hazard ratio (HR) 0.22 (95% confidence interval [CI] 0.15-0.32); PROpel rPFS HR 0.23 (95% CI 0.12-0.43). Clinical benefit was also observed in terms of overall survival: PROfound HR 0.63 (95% CI 0.42-0.95); PROpel HR 0.29 (95% CI 0.14-0.56). We provide a comprehensive overview of the utility of olaparib for patients with mCRPC harboring a BRCAm. Key clinical and safety data in BRCAm subgroup populations are discussed, predominantly based on findings from PROfound and PROpel, as well as investigator-initiated studies, to help inform treatment decision-making in this patient population. We also discuss the importance of genetic testing to identify patients who may optimally benefit from treatment with olaparib, either as a monotherapy or in combination with abiraterone.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"445-466"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}