Rubraca (rucaparib) / Clovis, Pharma& Schweiz, Hikma, GHN Pharma - 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

Rucaparib in refractory pleural mesothelioma harboring somatic pathogenic BRCA1 and BRCA2 mutation. A report of two cases. (PubMed, Lung Cancer Manag) - "Targeted agents did not demonstrate a significant clinical benefit in mesothelioma treatment, nevertheless a small group of patients might harbor potentially actionable somatic mutations, as in homologous repair recombination genes. In this paper we report two cases of patients with heavily pretreated pleural mesothelioma that had a relevant clinical benefit with rucaparib treatment based on somatic BRCA 1 and BRCA 2 mutations detected through next generation sequencing."

Journal • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Rare Diseases • Solid Tumor • BRCA • BRCA1 • BRCA2

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

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

Clinicogenomic profile, treatment patterns, and outcomes of BRCA-mutated cancers: Real-world data from western India (ESMO Asia 2025) - "Among BRCA-positive, 35.4% (93/263) received PARPi mainly olaparib (81.7%) rucaparib (18.3%) with 11/93 breast cancer patients treated adjuvantly; ORR was 90.5% for metastatic breast cancer & 88.9% for ovarian cancer. BRCA mutations serve as key therapeutic targets in ovarian and breast cancers; advancement in testing and expanded PARP inhibitor access have markedly enhanced clinical outcomes."

Clinical • Real-world • Real-world evidence • Breast Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • TP53

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

An atlas of ex vivo drug sensitivity profiles in 666 clinical glioblastoma samples revealed distinct survival-associated networks (SNO 2025) - P=N/A | "Eleven drugs were tested, including DNA-damaging agents (lomustine, carboplatin, temozolomide, procarbazine, irinotecan, etoposide) and targeted agents (abemaciclib, dabrafenib, osimertinib, rucaparib, trametinib). Longitudinal sampling revealed dynamic changes in drug sensitivity, reflecting evolutionary tumor biology. This ex vivo drug sensitivity atlas reveals distinct, non-random survival-associated clustering patterns that reflect underlying glioblastoma cellular physiologies and may inform future clinical trial designs."

Preclinical • Brain Cancer • Glioblastoma • Glioma • Solid Tumor

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

A Study of Rucaparib and Nivolumab in People With Leiomyosarcoma (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Completed ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Nov 2026 | Trial primary completion date: Jun 2025 ➔ Nov 2026

Enrollment closed • Trial completion date • Trial primary completion date • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor

Optimized dose schedule of rucaparib and liposomal irinotecan/5-fluorouracil in metastatic gastrointestinal cancers: A phase 1 study. (PubMed, Cancer) - "This optimized dosing schedule successfully established the MTD for RUB with nal-IRI and 5-FU, overcoming prior challenges with PARP inhibitor and irinotecan combinations. The promising ORR and DCR support further evaluation of this regimen in advanced GI malignancies."

Journal • P1 data • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • ATM • BRCA • HRD

SUO 2025: Efficacy of Rucaparib vs Physician’s Choice in Patients with BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer by Age: Results from the TRITON3 Study (UroToday) - "In the overall BRCA-mutated population, rucaparib continued to demonstrate a meaningful rPFS advantage, with a median rPFS of 11.2 months versus 6.4 months with physician’s choice of therapy, corresponding to an HR of 0.50 (95 percent CI, 0.36 to 0.69). The forest plot showed consistent benefit across all age groups....In an additional exploratory look at the oldest patients, those aged 81 years or older, rucaparib continued to show meaningful activity."

P3 data • Castration-Resistant Prostate Cancer

ARIANES: Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (clinicaltrials.gov) - P2 | N=130 | Terminated | Sponsor: Gustave Roussy, Cancer Campus, Grand Paris | Suspended ➔ Terminated; Bankruptcy of partner: Clovis

Pan tumor • Platinum sensitive • Trial termination • Bladder Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • ATM • BARD1 • BRCA1 • BRCA2 • BRIP1 • CDK12 • CHEK2 • DRD • FANCA • IL2 • NBN • RAD51 • RAD51C • RAD51D • RAD54L

PARPi and myeloid neoplasms; the Italian MITO-MaNGO experience based on a multicentric survey. (PubMed, ESMO Open) - "While this survey is meant as hypotheses-generating, PrMN represent a rare but clinically relevant complication, particularly uncommon when PARPi are administered as first-line therapy. Their occurrence does not appear to be associated with the specific PARPi used or with BRCA mutation status. Early detection, monitoring, and identification of predictive factors are crucial as ovarian cancer outcomes improve and treatment exposure increases."

Clinical • Journal • Acute Myelogenous Leukemia • Gynecologic Cancers • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Solid Tumor • BRCA

PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: Rationale, Mechanisms, and Clinical Applications. (PubMed, Eur Urol Oncol) - "Promising results have led to the approval of several PARPi agents as monotherapy or in combination with ARPIs in selected or unselected patients when chemotherapy is not clinically indicated. However, some questions remain regarding patient selection and treatment sequencing."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • PALB2

An atlas of ex vivo drug sensitivity profiles in 666 clinical glioblastoma samples revealed distinct survival-associated networks (WFNOS 2025) - P=N/A | "Eleven drugs were tested, including DNA-damaging agents (lomustine, carboplatin, temozolomide, procarbazine, irinotecan, etoposide) and targeted agents (abemaciclib, dabrafenib, osimertinib, rucaparib, trametinib). Longitudinal sampling revealed dynamic changes in drug sensitivity, reflecting evolutionary tumor biology. This ex vivo drug sensitivity atlas reveals distinct, non-random survival-associated clustering patterns that reflect underlying glioblastoma cellular physiologies and may inform future clinical trial designs."

Preclinical • Brain Cancer • Glioblastoma • Glioma • Solid Tumor

Radiosensitization Effect of PARP Inhibitor Talazoparib Involves Decreasing Mitochondrial Membrane Potential and Induction of Cellular Senescence. (PubMed, Curr Issues Mol Biol) - "ER10 values for talazoparib, olaparib rucaparib, ABT888 and niraparib were 1.5, 1.8, 2.8, 1.4, and 1.4, respectively. When the p21 gene was knocked down, both the decrease in mitochondrial membrane potential and senescence level were attenuated, suggesting that p21 is involved in senescence induction after γ-irradiation combined with talazoparib treatment. Taken together, we showed that PARP inhibitor talazoparib treatment in combination with γ-irradiation causes cellular senescence in lung cancer cells, involving p21 function."

Journal • Lung Cancer • Oncology • Solid Tumor • CDKN1A

Computational Chemistry Advances in the Development of PARP1 Inhibitors for Breast Cancer Therapy. (PubMed, Pharmaceuticals (Basel)) - "Some of the most prominent examples are Olaparib (IC50 = 5 nM), Rucaparib (IC50 = 7 nM), and Talazoparib (IC50 = 1 nM), which were optimized with docking scores between -9.0 to -9.3 kcal/mol and validated by in vitro and in vivo assays, achieving 60-80% inhibition of tumor growth in BRCA-mutated models and achieving up to 21-month improvement in progression-free survival in clinical trials of BRCA-mutated breast and ovarian cancer patients. Employing computation and experimental verification in a hybrid strategy have brought next-generation inhibitors to the clinic with accelerated development, higher efficacy, and personalized treatment for breast cancer patients. Future approaches, including AI-aided generative models and multi-omics integration, have the promise to further refine inhibitor design, paving the way for precision oncology."

Journal • Review • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD

"Outcomes of patients with pancreatic cancer having received biomarker-guided therapy based on the recommendations by a molecular tumor board" (DGHO 2025) - "Remissions were observed under pembrolizumab (MSH6 mutation), pemigatinib (FGFR2–G3BP2 fusion) and rucaparib (PALB2 mutation). Stable disease was achieved using gemcitabine-zolbetuximab combination therapy (CLDN18.2 IHC positive) and trametinib (GATM–RAF1 fusion)... A subset of PDAC patients can benefit from biomarker-guided non-standard treatment recommendations by an MTB. Especially patients with KRAS wild-type PDAC or with suspected/unknown deficiencies in homologous recombination or mismatch repair should be enrolled in the MTB. In future, proteomic tumor characterization may open further treatment avenues."

Biomarker • Clinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CLDN18 • FGFR2 • G3BP2 • KRAS • MSH6 • PALB2

Impact of PARP Inhibitor and Platinum Therapy on Clonal Hematopoiesis (ASH 2023) - "Patients were treated with a variety of PARPi including Olaparib (n=48), Talazoparib (n=33), Rucaparib (n = 13) and Niraparib (n = 6.) Of the 418 patients, 45 individuals harbored an HRD germline mutation...The percentage of Trp53 R172H cells in the blood was measured by flow cytometry at baseline (6 weeks after transplantation) and after treatment with vehicle alone, Talazoparib or Olaparib daily, or cisplatin weekly, for 4 weeks...Indeed, our data suggest the opposite, with the fitness advantage of DDR gene-mutated HSPCs lost in cells with a heterozygous Brca1-mutations. These data suggest that PARPi therapy may have less of an impact on leukemia risk compared to carboplatin and in fact may show synergistic effects with HRD in blocking the competitive advantage of DDR CH during genotoxic stress."

Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ASXL1 • BRCA1 • BRCA2 • CHEK2 • DNMT3A • HRD • JAK2 • PPM1D • SF3B1 • SRSF2 • TET2

BrUOG360: A phase Ib/II study of copanlisib in combination with rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). (PubMed, Cancer Res Commun) - "Copa/R had a favorable safety profile with a signal of efficacy supporting future studies of PARPi with PI3Ki."

Journal • P1/2 data • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • FANCA • PTEN • RAD51C

The Real-World Impact of PARP Inhibitor Maintenance Therapy in High Grade Serous Tubo-Ovarian and Peritoneal Cancers. (PubMed, Cancers (Basel)) - "BRCA2 germline-mutated patients obtained significantly greater benefit from olaparib compared to BRCA1-mutated patients. PFS benefit from niraparib (primary or recurrent setting) is comparable to clinical trials. There was no difference in benefit between niraparib and rucaparib in the recurrent setting."

Journal • Real-world evidence • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD

EFFICACY OF RUCAPARIB VS PHYSICIAN’S CHOICE IN PATIENTS WITH BRCA-MUTATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER BY AGE: RESULTS FROM THE TRITON3 STUDY (SUO 2025) - "Funding: Clovis Oncology and pharma& GmbH Introduction: In TRITON3, rucaparib significantly improved radiographic progression-free survival (rPFS) compared with physician’s choice of therapy, either docetaxel or an androgen-receptor pathway inhibitor (ARPI), in patients with BRCA-mutated, castration-resistant prostate cancer (mCRPC). Rucaparib consistently improved rPFS across all age groups including in older patients, and the safety profile was generally consistent across age groups. These findings support the use of rucaparib as a treatment option in patients with BRCA-mutated mCRPC regardless of age."

Clinical • Metastases • Anemia • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2