Abstract 2041P
Background
Pts with a germline BRCA pathogenic variant (gBRCA-PVs) and aHGOC report increased HAEs with platinum salts (PSs), for a possible more susceptibility of the hemopoietic stem cells to to DNA damaging agents. Also, MDS/AML cells seem to be enriched in gBRCA-PVs. The risk of PARPi-related HAEs and MDS/AML according to gBRCA-PV status in currently unknown.
Methods
We conducted a retrospective single-centre study to evaluate HAEs³G2 and MDS/AML in pts with aHGOC receving PARPi, according to the presence of a gBRCA-PV. Pts included had received a PARPi as maintenance therapy for ≥8 weeks, in any line of therapy, from Feb 2017 to Dec 2022, and had known gBRCA status. HAEs were identified by electronic medical record review, classified per CTCAE v5.0 and expressed as proportion of patients with at least one event. Onset of AML/MDS was tracked also beyond the end of treatment with PARPi (possible later occurrence), up to the last follow-up. Correlative analyses were performed (significance at p-value<0.05).
Results
166 pts were included: 95 (57%) had a gBRCA-PV. Patient characteristics, HAEs and MDS/AML are reported in in the table. At univariate analysis, gBRCA-PV status was not associated with PARPi-related HAEs, but was correlated with appearance of MDSs (9/95 vs. 1/71; p=0.04), which led to most of PARPi-discontinuations due to HAE/MDS/AML (12/95 vs. 2/71; p=0.02); 3/10 MDSs occurred during PARPi. Table: 2041P
Patient characteristics and HAEs
| gBRCA-PV+ N=95 | gBRCA-PV- N=71 | p | |
| Age at baseline, mean (SD) | 56.6 (8.9) | 60.1 (9.9) | .01 |
| Line of PARPi, median (IQR) | 2 (1-3) | 2 (1-3) | .79 |
| Type of PARPi | <.001 | ||
| Olaparib - % | 61% | 19% | |
| Niraparib - % | 21% | 29% | |
| Rucaparib - % | 9% | 1% | |
| Previous chemotherapy for other cancers - % | 10 | 4 | .79 |
| N° of cycles of PARPi, median (IQR) | 11 (8-24) | 13 (6-22) | .34 |
| HAEs - % of pts with at least one event | |||
| Any HAE* ³G2 | 47% | 28% | .67 |
| A ³G2 | 33% | 16% | .55 |
| N ³G2 | 20% | 14% | .37 |
| T ³G2 | 10% | 6% | .83 |
| MDS/AML | 10% | 2% | .16 |
| MDS | 9% | 1% | .04 |
| AML | 2% | 1% | 1.00 |
| Hospitalization for HAE | 3% | 2% | 1.00 |
| Dose reduction for HAE | 25% | 16% | .61 |
| Dose delay for HAE | 30% | 18% | .70 |
| Discontinuation for HAE or MDS/AML | 11% | 1% | .02 |
*A (anemia), N (neutropenia) or T (thrombocytopenia).
Conclusions
Unlike PSs, gBRCA-PVs are not associated with PARPi-related HAEs in pts with aHGOC. MDSs are more frequent in gBRCA-PV carriers. The interaction between gBRCA-PV, MDSs and PARPi warrants further investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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