Abstract 2148P
Background
VTE is a leading cause of death in pts with cancer, regardless of type. aHGOC is burdened by an VTE incidence of 20% and is listed as a high-risk malignancy for VTE. Treatment of aHGOC includes chemotherapy, bevacizumab and PARPi. Preclinical studies showed that the inhibition of PARP-1 could reduce endothelial dysfunction. Therefore, therapy with PARPi may potentially reduce the risk of VTE.
Methods
We conducted a retrospective single-centre observational study to describe rates, patterns and prognostic role of VTE events in patients with aHGOC receiving PARPi without bevacizumab. Pts included had received any PARPi for at least 8 weeks in any line of therapy, from Feb 2017 to Dec 2022. VTE events were identified by electronic medical record review and classified per CTCAE v5.0. Descriptive statistical analyses were performed for association with clinical outcomes (significance at p-value<0.05)
Results
Overall 166 pts were included. Baseline patients’ characteristics and outcomes are reported in the table. The baseline risk of VTE event was low, according to ONKOTEV and Khorana score. After a median follow-up of 38.5 months, only 5 (3%) pts experienced a VTE event on PARPi: 1 superficial thrombosis (G1), 1 deep venous thrombosis (G2) and 3 asymptomatic pulmonary embolisms (G3). No treatment discontinuation due to VTE occurred and all the events were treated with low-molecular-weight heparins. The median time to VTE was 5.5 months (95% CI, 1.6-9.4) and median time from VTE to disease progression was 1.8 months (95% CI, 1.3-2.4). Table: 2148P
VTE N=5 | Non-VTE N=161 | p | |
Age at baseline, mean (SD) | 63.8 (11.8) | 57.9 (9.4) | .17 |
Previous VTE, % | 20% | 11% | .46 |
Baseline Khorana score, median (IQR) | 1 (1-1) | 1 (1-1) | .97 |
Baseline ONKOTEV, median (IQR) | 1 (1-2) | 1 (1-1) | .06 |
Anticoagulant prophylaxis at baseline, % | 0% | 8% | 1.00 |
Bevacizumab within 6 months, % | 0% | 5% | 1.00 |
Line of PARPi, median (IQR) | 2 (2-4) | 2 (1-3) | .26 |
Type of PARPi | .12 | ||
Olaparib, % | 100% | 53% | |
Niraparib, % | 0% | 39% | |
Rucaparib, % | 0% | 7% | |
Number of cycles of therapy with PARPi, median (IQR) | 7 (5-8) | 12 (7-22) | .21 |
PARPi exposure, median (mo) (95% CI) | 7.8 (6.1-8.7) | 13.0 (8.9-17.1) | .72 |
PARPi-PFS, median (mo) (95% CI) | 7.4 (6.1-8.6) | 13.6 (9.5-17.7) | .38 |
Conclusions
Among pts with aHGOC receiving PARPi, VTE events were substantially low, suggesting a possible protective role of PARPi leading to reduced VTE risk. Conceivably, VTE occurrence may anticipate radiological disease progression.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D. Trapani: Other, EMA Healthcare Professional Working Party (HCPWP), Member: European Medicines Agency (EMA); Other, EML Cancer Medicines Working Group (CMWG), Member: World Health Organization (WHO); Other, Strategic Advisory Group of Experts on In Vitro Diagnostics (SAGE IVD), Chair: World Health Organization (WHO). N. Fazio: Financial Interests, Personal, Advisory Board: Novartis, Merck, AAA, Hutchinson MediPharma, MSD; Financial Interests, Personal, Invited Speaker: AAA, Merck; Financial Interests, Institutional, Local PI: Astellas, MSD, BeiGene, Incyte, Nucana, Ipsen, 4SC, Fibrogen; Financial Interests, Institutional, Research Grant: Ipsen, AAA, Merck; Non-Financial Interests, Other, Steering committee: SPARC Europe; Non-Financial Interests, Member of Board of Directors: ENETS; Non-Financial Interests, Other, Member of the GI and NET Faculties: ESMO; Non-Financial Interests, Other, Internal reviewer of NET Guidelines: AIOM. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Coordinating PI, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, GSK, Pfizer, Immunogen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO (Alleanza Contro il Tumore Ovarico). All other authors have declared no conflicts of interest.
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