Lynparza (olaparib) / Merck (MSD), AstraZeneca - LARVOL DELTA

'OLAP' (OLAparib Regulatory Post-marketing Surveillance) (clinicaltrials.gov) - P=N/A | N=662 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor

PARP inhibitor-induced anti-tumour chemokine response is suppressed by dipeptidyl peptidase 4 (DPP4) in ovarian cancer (Nature) - "In our study, olaparib induced the chemokines mCCL5 and mCXCL10 in a dose-dependent manner in HRD and HRP ovarian cancer cells. An optimised olaparib concentration induced chemokine release and improved survival in the syngeneic HRD ovarian cancer mouse model but not in immunocompromised mice, likely promoting synergism of immune activation and tumour cell cytotoxicity. Overexpression of mCCL5- and mCXCL10-cleaving mDPP4 induced resistance to olaparib in the HRD mouse model. Conversely, mDPP4 inhibition led to the reversal of intrinsic PARPi resistance in the HRP mouse model."

Preclinical • Ovarian Cancer

THOR: Pembrolizumab and Olaparib Treatment of Extensive Small Cell Lung Cancer (ES-SCLC) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS | Trial completion date: Oct 2026 ➔ Jul 2027 | Trial primary completion date: Oct 2026 ➔ Jul 2027

Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • PD-L1

A novel 18F-labeled brain penetrant PET ligand for imaging poly(ADP-ribose) polymerase-1 (SNMMI 2025) - "Blocking studies with AZD9574, Olaparib, Rucaparib, Veliparib, and Pamiparib significantly reduced intracellular radiotracer uptake, while no significant reduction was observed with UPF-1035, a PARP2-specific inhibitor (Fig. The radiotracer 18F-AZD9574 was synthesized following a previously established protocol (Fig. 1A). Western blot analysis confirmed substantial PARP1 expression in the U87-MG (glioblastoma), 22Rv1 (prostate), PSN-1 (pancreatic), MDA-MB-436 (breast), and MDA-MB-231 (breast) cancer cell lines (Fig."

Brain Cancer • Breast Cancer • Glioblastoma • Oncology • Pancreatic Cancer • Solid Tumor • PARP1 • PARP2

Targeting the xC- system PET monitors therapeutic efficacy of combining PARP inhibitor with immunotherapy in hepatocellular carcinoma treatment. (SNMMI 2025) - " Hepa1-6 tumor-bearing C57BL/6j mice were split into four groups at random, namely vehicle control, anti-PDL1 alone, Olaparib (a PARPi) alone, or a combination of anti-PDL1 and Olaparib... Imaging results from [18F]-FASu PET/CT showed that tumours in the control group had a lower tumour-to-background ratio (TBR) with a mean SUVmax value of 1.76 and in the combination treatment group with a mean value of 1. While [18F]-FDG assay results did not observe differences between the groups. Immunohistochemistry showed that the expression of the corresponding Ki67 was significantly lower in the combination therapy group compared with the other three groups."

Clinical • IO biomarker • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • SLC7A11

Formerly breast cancer: How many patients are potential candidates of a combined endocrine therapy? (DGS 2025) - "Objective: This retrospective case evaluation evaluates the number of potential candidates for combined endocrine therapy (Olaparib, Abemaciclib and Ribociclib) in the Real-World Context. The broad indication criteria of the Natale study could increase the workload in the clinic, since more frequent doctor-patient interactions are required. However, it remains unclear how therapy recommendations affect actual treatment, as increased visits and potential side effects could affect the compliance of patients."

Clinical • Breast Cancer • Oncology • Solid Tumor

How to choose optimal adjuvant therapies for high-risk hormone receptor-positive, HER2-negative breast cancer after chemotherapy? (PubMed, Acta Oncol) - "Optimal patient selection for these often toxic treatments remains partially unclear and is the focus of intensive research. In the near future, monitoring ctDNA may enable treatment de-escalation for selected high-risk patients. The rise of perioperative immunological therapies, new CDK4-specific inhibitors, and targeted endocrine treatments can lead to a notably favorable prognosis for many previously high-risk HR+/HER2- breast cancers. Future research should prioritize predictive biomarkers and personalized approaches to optimize treatment efficacy, ensure more equal access to treatments, and minimize overtreatment."

Journal • Review • Breast Cancer • Endocrine Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • HER-2

AZ redefines...ovarian cancer playbook (Korea Biomedical Review) - P3 | N=450 | SOLO-1 (NCT01844986) | Sponsor: AstraZeneca | "The event also highlighted Lynparza’s leadership in ovarian cancer treatment, reinforced by unprecedented long-term data from the SOLO-1 study....In SOLO-1, 67 percent of patients treated with first-line Lynparza maintenance were alive at seven years, compared to 46.5 percent in the placebo arm. 'Roughly two out of three women with BRCA-mutated ovarian cancer remained alive seven years after starting Lynparza'..."

P3 data • Ovarian Cancer

AZ redefines endometrial...cancer playbook (Korea Biomedical Review) - P3 | N=813 | DUO-E (NCT04269200) | Sponsor: AstraZeneca | "According to results from the global phase 3 DUO-E trial, which Lee participated in, the median progression-free survival (PFS) for pMMR patients treated with the combination maintenance therapy of Imfinzi and Lynparza reached 15 months, compared to 9.7 months for those receiving chemotherapy alone. Although overall survival (OS) data are not yet mature, early trends favor the Lynparza-inclusive regimen."

P3 data • pMMR • Endometrial Cancer

Impact of Olaparib, Niraparib, Rucaparib therapies on Newly Diagnosed and Relapsed Ovarian Cancer -Systematic Review and Meta-Analysis. (PubMed, Asian Pac J Cancer Prev) - "PARPi are an effective therapy in both newly discovered and relapsed. Although there is a modest rise in the frequency of severe adverse reactions, they are usually handled well."

Journal • Retrospective data • Review • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia

A phase II study of olaparib in patients (pts) with advanced biliary tract cancer (aBTC) with aberrant homologous recombinant repair (HRR) mutations (ESMO-GI 2025) - "The primary endpoint of PFS was achieved from olaparib in pts with aBTC with mutations associated with HRR. Tx was well tolerated with AE profile consistent olaparib. PARPi represents a potential Tx in HRR deficient aBTC including opportunities to investigate novel combination Tx strategies moving forward."

Clinical • Metastases • P2 data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2 • PALB2

Cognition-Guide, a multicenter phase-II-Umbrella study to examine genomically controlled, post-neoadjuvant treatment in patients with early breast cancer and high risk of recurrence after neoadjuvant chemotherapy (DGS 2025) - "As part of cognition, tumorresidua after a neoadjuvant chemotherapy in patients with early BC and a high risk of relapse (TNBC/Her2+ BC with non-PCR; hr+/her2- BC with non-PCR and CPS-EG score ≥ 3 or OPN+ and CPS-EG score ≥ 2) Full genome/whche-exomes and RNA sequencing analyzed in order to proof of a suitable biomarker, a subsequent assignment to one of six treatment arms within Cognition-Guide (atezolizumab, inavolisib, IpaTasertib, Olaparib, Sacituzumab Govitecan, Trastuzumab) or-in contraindication or- missing biomarker - to enable a low -observation. 240 patients are recruited at at least 9 German locations to demonstrate an IDFS improvement of 10 %(Power 90 %, level of significance 5 %) compared to historical controls. Updated data will be presented at the time of the congress."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Updated Guidelines for the Diagnosis and Treatment of Endometrial Carcinoma: The Polish Society of Gynecological Oncology (2025v). (PubMed, Curr Oncol) - "For MMRp-positive cases, the 2025 version introduces the use of Olaparib alongside Durvalumab and CHTH. HER2-positive MMRp serous carcinoma remains eligible for trastuzumab in combination with CHTH...However, options for those previously treated with this combination are still under evaluation. This update ensures alignment with the latest international standards and reinforces evidence-based, personalized care for EC patients."

Clinical guideline • Journal • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • HER-2

Adipocytes Promote Cisplatin Resistance through Secreting A1BG and Regulating NAMPT/PARP1 Axis-Mediated DNA Repair in Osteosarcoma. (PubMed, Adv Sci (Weinh)) - "Importantly, pharmacological inhibition of NAMPT and PARP1 using FK886 and Olaparib, respectively, reversed Adi-CM-induced cisplatin resistance and restored cisplatin sensitivity in osteosarcoma cells, DIO mouse models, and patient-derived organoids. A novel link between obesity and cisplatin resistance in osteosarcoma is established, highlighting the A1BG/NAMPT/PARP1 axis as a critical driver. Targeting this axis may represent a promising therapeutic strategy for overcoming obesity-associated chemoresistance in osteosarcoma."

Journal • Genetic Disorders • Obesity • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • NAMPT • PARP1

Label Update for AstraZeneca's Olaparib Cleared by CDSCO Panel (Medical Dialogues) - "In a recent regulatory update, the Subject Expert Committee (SEC) under the Oncology division of the Central Drugs Standard Control Organisation (CDSCO) has approved the proposed revision to the prescribing information for Olaparib Tablets 100 mg and 150 mg, submitted by AstraZeneca Pharma India Limited. The recommendation was made during the 19th SEC (Oncology) meeting held on 5th June 2025 at CDSCO headquarters in New Delhi. The proposal was based on the updated Company Core Data Sheet (CCDS) for Olaparib, reflecting changes to the drug’s safety and pharmacological profile."

Regulatory • Breast Cancer • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer

Synergistic strategies: ADC-PARP inhibitor combinations in triple-negative breast cancer therapy. (PubMed, Pathol Res Pract) - "ADCs like sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) target cytotoxic payloads with specificity, whereas PARPis like olaparib, rucaparib, niraparib, and talazoparib cause synthetic lethality in homologous recombination repair (HRR)-deficient tumors. Future directions include biomarker-driven patient selection, combination with immune checkpoint inhibitors, and advancement in next-generation ADCs. The synergistic potential of ADC-PARPi combinations provides a new avenue for overcoming TNBC resistance, enhancing treatment outcomes, and widening therapeutic strategies for this challenging disease."

IO biomarker • Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • HRD

MAPPING THE DIVERSITY OF IMMUNOTHERAPY IN TRIPLE NEGATIVE BREAST CANCER: TREATMENTS, OUTCOMES, AND SIDE-EFFECTS WITH IMMUNE CHECKPOINT INHIBITORS (MASCC-ISOO 2025) - "Results Treatments included monotherapies with PD-1 inhibitors (e.g., Pembrolizumab, Nivolumab), PD-L1 inhibitors (e.g., Atezolizumab, Durvalumab), and combination therapies with chemotherapy (e.g., Nab-paclitaxel, carboplatin), targeted therapies (e.g., Apatinib, Olaparib), and radiotherapy (e.g., stereotactic body radiotherapy). While immune-related AEs were common, they were largely manageable. Further research into novel combinations and biomarker validation is essential to advance precision immunotherapy for TNBC."

Adverse events • Checkpoint inhibition • IO biomarker • Tumor mutational burden • Breast Cancer • Fatigue • Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • TMB

Association of Homologous Recombination Repair Alterations With Outcomes in Patients with Metastatic Hormone-Sensitive Prostate Cancer. (PubMed, Clin Cancer Res) - "To date, this is the largest real-world natural history study evaluating the association of HRRalt with outcomes in the mHSPC setting. These data may inform future clinical trial design and counseling of these patients."

Journal • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Dr McKay on Data for Olaparib Plus Radium-223 in CRPC With Bone Metastases (OncLive) - "Rana R. McKay, MD, FASCO, discusses data the combination of olaparib plus radium-223 vs radium-223 monotherapy in castration-resistant prostate cancer."

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The importance of T-cell receptor excision circle and B cell receptor ?-deletion element levels in the efficacy of metastatic ovarian cancer therapy (ESMO-GC 2025) - "Methods The aim of this work was to evaluate the diversity of T-cell and B-cell receptors for the effectiveness of olaparib therapy for generalized ovarian cancer...Conclusions The prognostic significance of TREC and KREC has been determined. Further development of immuno-oncology will allow taking into account changes in TREC and KREC indices in dynamics and using the prognostic significance of these changes on treatment outcomes and survival rates."

Clinical • IO biomarker • Metastases • Oncology • Ovarian Cancer • Solid Tumor

Predictive factors of hematological toxicity in patients treated with PARPi in ovarian cancer (ESMO-GC 2025) - "Patients included received NIRAPARIB, OLAPARIB +/- BEVACIZUMAB according to molecular profile and the clinical risk. Clinical criteria and intensity of cytotoxic therapy delivered prior to PARPi initiation trend to be important such as baseline kidney function, apparition of hematotoxicity during chemotherapy and total dose of carboplatin and should alert us and lead to discuss the intensity of treatments for patients that will be potentially cured. Legal entity responsible for the study The authors."

Biomarker • Clinical • Oncology • Ovarian Cancer • Solid Tumor

Impact of BRCA mutation location on PARPi response in advanced high-grade serous ovarian cancer (HGSOC): Real-world data from two tertiary university hospitals in Spain (ESMO-GC 2025) - "30 pts received first-line PARPi (26 olaparib and 4 niraparib). Median follow-up was 39 m (4-123). Conclusions In our study, BRCA1 RING or BRCT mutations showed poor PARPi response and survival, consistent with previous reports."

Clinical • Metastases • Real-world • Real-world evidence • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • PALB2 • RAD51

Cardiovascular toxicities with first-line maintenance olaparib (ola) + bevacizumab (bev) in advanced ovarian cancer (aOC): A real-world analysis (ESMO-GC 2025) - "Table: 86P ola+bev vs bev HR (95% CI) ola+bev vs ola HR (95% CI) ola vs bev HR (95% CI) PE 0.76 (0.57-1.03) 1.61 (1.13-2.30) 0.44 (0.26-0.73) DVT 0.60 (0.38-0.94) 1.26 (0.74-2.16) 0.63 (0.35-1.64) Hypertension 0.80 (0.68-0.93) 1.45 (1.22-1.74) 0.53 (0.41-0.67) Stroke 1.02 (0.52-2.03) 1.37 (0.66-2.85) 0.43 (0.15-1.26) AF 0.82 (0.54-1.24) 1.22 (0.78-1.93) 0.52 (0.29-0.94) IMA 0.66 (0.33-1.34) 1.69 (0.69-4.14) 0.71 (0.21-2.32) HF 0.97 (0.66-1.42) 2.88 (1.67-4.96) 0.68 (0.36-1.30) Conclusions In our real-world study, ola plus bev significantly mitigated the risk of cardiovascular events compared to bev alone. Albeit these findings may be influenced by a higher discontinuation rate of the antiangiogenic treatment, the safety profile of the combination remains favorable."

Clinical • Metastases • Real-world • Real-world evidence • Oncology • Ovarian Cancer • Solid Tumor

Efficacy and safety of olaparib plus letrozole in metastatic endometrial cancer: A novel therapeutic approach (ESMO-GC 2025) - "Additionally, the ENGOT-EN3/PALEO phase II trial has shown promising results for palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer, supporting the rationale for hormone-based combination strategies (2). Conclusions The combination of olaparib and letrozole represents a promising therapeutic strategy for patients with HR-positive, HRR-deficient MEC, leveraging dual inhibition of DNA repair and hormonal signaling pathways. These findings are consistent with prior studies and support further investigation in larger, randomized trials."

Clinical • Metastases • Endometrial Cancer • Oncology • Solid Tumor • ER • HRD

Durvalumab plus carboplatin/paclitaxel followed by durvalumab with/without olaparib as first-line treatment for endometrial cancer: Progression-free survival and safety by age above/below 70 years and with/without clinical obesity in the DUO-E trial (ESMO-GC 2025) - P3 | "Editorial acknowledgement Medical writing assistance was provided by Sarah Mancini, PhD, CMC Connect, funded by AstraZeneca. Legal entity responsible for the study AstraZeneca."

Clinical • Endometrial Cancer • Oncology • Solid Tumor