Zejula (niraparib) / Medison, GSK, ZAI Lab, J&J, Takeda - LARVOL DELTA

PARP inhibitors and the rising incidence of secondary myelodysplastic syndrome and acute myeloid leukemia: A comprehensive meta-analysis (ASH 2025) - " The combined cohort included 106,793 patients treated with PARPi, including olaparib, niraparib, rucaparib, and talazoparib. This meta-analysis highlights that while MDS and AML are uncommon complications of PARP inhibitor therapy, their occurrence is clinically meaningful, with an overall incidence of approximately 1.5%. The risk notably increases with extended treatment duration and is associated with substantial mortality. These results underscore the importance of vigilant hematologic monitoring in patients receiving long-term PARP inhibitors and emphasize the need for prospective studies to discover predictive biomarkers and enhance personalized risk stratification."

Retrospective data • Acute Myelogenous Leukemia • Breast Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Ovarian Cancer • Solid Tumor • BRCA

Hematologic toxicities associated with PARP inhibitors: Real world pharmacovigilance updated study using faers database with era-trend evaluation and serious outcome modeling (ASH 2025) - "We employed 4 PARPi drugs (included generic and brand names),olaparib, niraparib, rucaparib, and talazoparib were coded as a primary suspect drug. This is the largest real-world study to date demonstrating specific hematologic AEs withPARPi. Our results show distinct and varying patterns of hematologic toxicity across PARPi, with thestrongest disproportionality observed for cytopenias, particularly thrombocytopenia, leukopenia, andanemia, and notable signals for MDS. Recognizing these patterns will help clinicians better monitor andmanage patients receiving PARPi therapy."

Adverse events • Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Breast Cancer • Leukopenia • Myelodysplastic Syndrome • Ovarian Cancer • Solid Tumor • Thrombocytopenia

PARP inhibition by talazoparib results in leukemia cell death via induction of myeloid differentiation (ASH 2025) - "Across multiple cell lines, talazoparibconsistently exhibited more potent dose dependent anti-proliferative effects on AML growth than otherPARP inhibitors (olaparib,niraparib, rucaparib). We demonstrate here that talazoparib exerts potent anti-tumor activity across an array ofhuman AML cell lines, patient samples, and an in vivo xenograft model in part due to induction ofmyeloid differentiation. This was characterized by attenuated growth, prominent morphological andmolecular hallmarks, and increased cell death. Our results suggest that talazoparib may represent anovel mutation-agnostic differentiation therapy for acute myeloid leukemia."

Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Ovarian Cancer • BRCA1 • BRCA2 • CD14 • CDK2 • IL1B • ITGAM

Chemotherapy-Free Niraparib–Dostarlimab Regimen Achieves 50% pCR in Germline BRCA–Mutated TNBC (DocWire) - "At the time of surgery, 23 patients (50%) achieved a pCR (90% confidence interval [CI], 37.1%–62.9%), exceeding the prespecified efficacy benchmark of >43%. The study team observed residual disease in 12 patients (26.1%), including 4 with RCB-I, 5 with RCB-II, 2 with RCB-III, and one not calculable. An additional 11 patients (23.9%) crossed over to additional preoperative therapy prior to surgery....The pCR rates were identical between treatment strategies, with 50% pCR in the upfront combination group (Arm A; 90% CI, 31.1%–68.9%) and 50% in the niraparib lead-in group (Arm B; 90% CI, 31.9%–68.1%)."

P2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Triple Negative Breast Cancer

Niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) in Chinese patients with breast cancer susceptibility gene (BRCA) altered metastatic castration-sensitive prostate cancer (mCSPC): Subgroup analysis of the phase III AMPLITUDE trial (ESMO Asia 2025) - P3 | "The Chinese BRCA-positive subgroup are consistent with those reported in the overall population of the AMPLITUDE trial, supporting the utility of early genomic testing and the incorporation of NIRA+AAP as a targeted therapeutic approach for Chinese patients with BRCA gene-altered mCSPC."

Clinical • Metastases • P3 data • Breast Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD

Impact of PARP inhibitor resistance on subsequent treatment outcomes and platinum sensitivity in advanced ovarian cancer: Insights from the National University Cancer Institute, Singapore (ESMO Asia 2025) - "This analysis included those who received 1L or second-line and beyond (≥2L) PARPi maintenance—Olaparib, Niraparib, or Rucaparib—between May 2020 and November 2024. Progression on PARPi in advanced OC correlates with reduced efficacy of subsequent therapies and high rates of platinum resistance. These findings emphasize the urgent need for novel, effective treatment strategies after PARPi failure to improve pt outcomes."

Clinical • Metastases • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD

Efficacy and Safety of Niraparib in Combination with Anlotinib Based on CA 125 Level in Newly Diagnosed Ovarian Cancer: An open-label, single arm, multicenter, prospective phase II trial (ESMO Asia 2025) - P2 | "TEAEs occurred in 19/22 (86.4%) pts including 4 (18.2%) pts with grade ≥3. The most common TEAEs include mucositis, hypertension, anemia, anorexia, diarrhea and fatigue.Conclusions Niraparib plus anlotinib shows promising efficacy and tolerable safety in newly diagnosed OC with elevated CA125 during niraparib maintenance therapy."

Clinical • Combination therapy • P2 data • Oncology • Ovarian Cancer • Solid Tumor • MUC16

Safety and efficacy of PARP inhibitors in metastatic castration-resistant prostate cancer with DNA damage repair alterations: A systematic review and meta-analysis of randomized controlled trials (ESMO Asia 2025) - "Risk of bias was assessed with Cochrane RoB 2.0. Seven RCTs evaluating olaparib, niraparib, rucaparib, and talazoparib in DDR-altered mCRPC were included. PARP inhibitors significantly prolong rPFS and improve OS in DDR-altered mCRPC, especially in BRCA1/2-mutated disease. However, this comes with an increased risk of SAEs, particularly hematologic events. These findings underscore the importance of individualized risk–benefit assessment, close monitoring, and judicious use of PARP inhibitors in routine practice for biomarker-selected mCRPC patients."

Metastases • Retrospective data • Review • Acute Myelogenous Leukemia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2

MAGED1 (NRAGE) inhibition enhances sensitivity to PARP inhibitors in BRCA-mutated breast cancer cell lines (ESMO Asia 2025) - "Cell viability was assessed by CytoFLEX after treatment with drugs (cisplatin, olaparib and niraparib) at several concentrations (0–300 μM) in Hs578T, HCC-1937 (BRCA1 5382insC), and BT-474 (BRCA2 c.0391C>A) breast cancer cell lines. Our study demonstrates that silencing of MAGED1 enhances sensitivity to PARP inhibitors in BRCA1/2-mutant breast cancer cell lines. These results suggest that MAGED1 is involved in HRD and could be a therapeutic target to enhance PARP inhibitor response in breast cancer."

Preclinical • Breast Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • BARD1 • BRCA • BRCA1 • BRCA2 • HRD • RAD51 • RNF8

Poly (ADP-ribose) polymerase (PARP) inhibitors approved for the treatment of cancer. (PubMed, Pharmacol Res) - "The FDA has approved four PARP inhibitors (olaparib, rucaparib, niraparib, and talazoparib) for the treatment of ovarian, breast, prostate, and pancreatic cancer...The Chinese NMPA has approved three PARP antagonists (fuzuloparib, pamiparib, senaparib) for the treatment of ovarian cancer. All seven of these drugs are orally bioavailable and fall within the criteria of Lipinski's rule of five. Drug resistance develops in most PARP-inhibitor-treated cancer patients within one or two years."

Journal • Review • Breast Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD

Real-world incidence and risk of myelodysplastic syndrome and acute myeloid leukemia secondary to PARP inhibitors in ovarian cancer. (PubMed, Clin Transl Oncol) - "PARPi are effective and generally with a manageable safety profile. However, secondary MDS and AML, though rare, remain serious adverse events with incompletely defined risk factors. The observed incidence, particularly with olaparib, is comparable to or higher than that reported in trials, though the sample size was limited. Close monitoring of hematologic AEs may be key to preventing these neoplasms."

Journal • Real-world evidence • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • BRCA

Comprehensive genomic profiling for homologous recombination deficiency guides PARP inhibitor therapy recommendations in ovarian cancer. (PubMed, Pathol Oncol Res) - "PARPi selection differed by HRD status, with niraparib favored in HR-proficient and olaparib in HRD-positive tumors. No additional profiling was required for PARPi therapy recommendation, and no incidental findings beyond the scope of HRD testing were detected. Molecular profiling with F1CDx proved to be a technically feasible, clinically impactful, and time-efficient assay, demonstrating its value in supporting molecular-guided PARPi therapy recommendations in the routine care of HGSOC patients."

Biomarker • Journal • Retrospective data • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD

Competing Beyond the First Mover: How Late to Market Analogues Navigate Pricing and Access in Major Global Markets (ISPOR-EU 2025) - "HTA, pricing outcomes and payer perceptions for ten analogues (such as Alecensa, Zejula, Rozlytrek, Eylea, Fasenra) were analysed across seven global markets (US, Germany, France, Spain, UK, Brazil, Canada). Several distinct pricing strategies (discounting, parity or premium) were observed which were highly dependent on the level of clinical differentiation vs. earlier to market options. Analogue assessment considered clinical and other non clinical factors that impacted their pricing and access success or failure which can potentially be used as a guide for future portfolio development and optimisation. Demonstrating clinical differentiation vs. earlier entrants is the critical factor translating into positive HTA outcomes and securing a price premium."

Clinical • Pricing

Maged1 inhibition enhances sensitivity to parp inhibitors in brca-mutated breast cancer cells (SABCS 2025) - "Cell viability was assessed by CytoFLEX after treatment with drugs (cisplatin, olaparib and niraparib) at several concentrations (0–300 µM) in Hs578T, HCC-1937 (BRCA1 5382insC), and BT-474 (BRCA2 c.0391C>A) breast cancer cell lines. Our study demonstrates that silencing of MAGED1 enhances sensitivity to PARP inhibitors in BRCA1/2-mutant breast cancer cell lines. These results suggest that MAGED1 is involved in HRD and could be a therapeutic target to enhance PARP inhibitor response in breast cancer."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BARD1 • BRCA • BRCA1 • BRCA2 • HRD • RAD51 • RNF8

Comparative Analysis of Maintenance Treatments in Patients with Newly Diagnosed Advanced Ovarian Cancer After First-Line Platinum-Based Regimens. (PubMed, Cancers (Basel)) - "PARPi efficacy depends strongly on BRCA and HRD status. Olaparib-based regimens provide the greatest clinical benefit with acceptable safety in BRCA+ and HRD+ disease, whereas PARPi appear to be of limited value in HRD-negative ovarian cancer."

Journal • Review • Fatigue • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • BRCA

Development of a liquid overlay-based three-dimensional cell culture panel for drug screening applications. (PubMed, Sci Rep) - "Afterwards, the cytostatic and cytotoxic responses of these models to three targeted anti-PARP therapies, Olaparib, Rucaparib and Niraparib, were analyzed, revealing their sensitivity. These results demonstrated that our liquid overlay-based technique provides both a large cell culture panel, whatever the tissue type or pathological level, and an automated drug screening process that could lead to highly predictive efficacy results."

Journal • Preclinical • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • PARP1

Clinical outcomes of combination PARP inhibitor and temozolomide therapy in recurrent glioma: Insights from a single institution experience (SNO 2025) - "PARPi included olaparib (n = 18) and niraparib (n = 1). This retrospective analysis supports the tolerability of combining PARPi with temozolomide in a real-world, heavily pretreated glioma population. Despite limited evidence of durable tumor control, the regimen provided transient disease stability in patients with few remaining options. These findings may inform treatment in compassionate or salvage settings particularly when alkylator treatment is considered, and highlight the need for prospective trials to identify response biomarkers and assess clinical utility."

Clinical • Clinical data • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oligodendroglioma • Solid Tumor • BRCA • CSF2 • IDH1

Niraparib induces hyperglycemia in ovarian cancer patients: a preliminary pilot study. (PubMed, Pharmacol Rep) - No abstract available

Journal • Diabetes • Oncology • Ovarian Cancer • Solid Tumor

Zai Lab Announces Updates to China’s National Reimbursement Drug List (FinancialContent) - "ZEJULA (niraparib) is renewed for the maintenance treatment of adult patients with platinum-sensitive, first-line and recurrent ovarian cancer."

Platinum sensitive • Reimbursement • Ovarian Cancer

Unveiling the power of PARP inhibitors: a meta-analysis on newly diagnosed advanced ovarian cancer maintenance therapy. (PubMed, Expert Rev Anticancer Ther) - "Notably, senaparib showed superior PFS efficacy compared to veliparib and niraparib. PARPi showed efficacy in improving PFS as maintenance therapy for newly diagnosed advanced OC, although no OS advantage was observed. PROSPERO (CRD420251020275)."

Journal • Retrospective data • Review • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD

Tbcrc 056: a phase 2 study of neoadjuvant niraparib with dostarlimab for patients with BRCA- or PALB2-mutated breast cancer: results from the TNBC cohorts (SABCS 2025) - "ConclusionsIn pts with gBRCAm early TNBC, 18 wks of targeted therapy using PARPi and anti-PD1 agents, with or without 3-week PARPi lead-in, resulted in a pCR rate of 50%, and a statistically significant increase in sTILs from BL to 3 wks. Further ongoing correlative work may identify best candidates for this non-chemotherapy-based approach."

Clinical • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • CD8 • ER • HER-2 • PALB2 • PD-L1

Outcomes of Immunotherapy in BRCA-Mutation Positive, Hormone-Receptor Positive, Breast Cancer: A Systematic Review (SABCS 2025) - "Mayer et al treated 18 patients with a combination of Niraparib and Dostarlimab in the neoadjuvant setting...Cortesi et al reported outcomes of Pembrolizumab and Carboplatin combination in 16 patients with gBRCA-m, HR+ m metastatic breast cancer...The addition of immunotherapy to chemotherapy provides an additional therapeutic option to combat BRCA-m, HR+ breast cancer with an acceptable safety profile. However, current studies are limited by the small sample sizes and the short follow-up times."

IO biomarker • Review • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2

NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov) - P2 | N=51 | Terminated | Sponsor: Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Dec 2027 ➔ Feb 2025 | Suspended ➔ Terminated; Abandon of the partner, GSK

Pan tumor • Platinum sensitive • Trial completion date • Trial termination • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Clear Cell Renal Cell Carcinoma • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Renal Cell Carcinoma • Solid Tumor • ARID1A • ARID2 • BARD1 • BRCA1 • BRCA2 • BRIP1 • CDK12 • CHEK2 • DRD • FANCA • HER-2 • IDH1 • IDH2 • NBN • PBRM1 • RAD51 • RAD51C • RAD51D • RAD54L

Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS (LUMOS2) study (WFNOS 2025) - P2 | "LUMOS2 currently has four active arms each with n=19 participants: paxalisib (PIK3CA-MTOR inhibitor) for participants with PIK3CA pathway alterations, or randomization to one of three target-agnostic options: AK104 (PD-1/CTLA-4 bispecific antibody), selinexor (selective inhibitor of nuclear export), or niraparib plus AK104 (PARP inhibitor plus AK104). Feasibility of molecular guided therapy in recurrent grade 2-3 glioma based on comprehensive genomic profiling is established with trial recruitment to date."

IO biomarker • Brain Cancer • Oncology • Solid Tumor • CTLA4 • MTAP • PD-1 • PIK3CA

Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS (LUMOS2) study (SNO 2025) - P2 | "LUMOS2 currently has four active arms each with n=19 participants: paxalisib (PIK3CA-MTOR inhibitor) for participants with PIK3CA pathway alterations, or randomization to one of three target-agnostic options: AK104 (PD-1/CTLA-4 bispecific antibody), selinexor (selective inhibitor of nuclear export), or niraparib plus AK104 (PARP inhibitor plus AK104). Feasibility of molecular guided therapy in recurrent grade 2-3 glioma based on comprehensive genomic profiling is established with trial recruitment to date."

IO biomarker • Brain Cancer • Glioma • Solid Tumor • CTLA4 • MTAP • PD-1 • PIK3CA