Abstract
We would like to comment on the letter from Dr. Armstrong related to our recent article published in this journal [ [1] O’Malley D.M. Oza A.M. Lorusso D. et al. Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma. Gynecol. Oncol. 2022; 167: 404-413https://doi.org/10.1016/j.ygyno.2022.08.021 Abstract Full Text Full Text PDF Scopus (2) Google Scholar ]. We reported exploratory analyses that identified a subset of patients who achieved an exceptional response to rucaparib maintenance therapy within the ARIEL3 trial. With long-term outcome data now available for both the upfront and recurrent ovarian cancer settings, it is known that patients receiving PARPi therapy are at heightened risk of developing MDS/AML [ [2] Nitecki R. Melamed A. Gockley A.A. et al. Incidence of myelodysplastic syndrome and acute myeloid leukemia in patients receiving poly-ADP ribose polymerase inhibitors for the treatment of solid tumors: a meta-analysis of randomized trials. Gynecol. Oncol. 2021; 161: 653-659https://doi.org/10.1016/j.ygyno.2021.03.011 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar , [3] Matulonis U.A. The rapid evolution of PARP inhibitor therapy for advanced ovarian cancer: lessons being learned and new questions emerging from phase 3 trial long-term outcome data. Gynecol. Oncol. 2022; 167: 401-403https://doi.org/10.1016/j.ygyno.2022.11.018 Abstract Full Text Full Text PDF Scopus (0) Google Scholar ]. Indeed, the letter from Dr Armstrong provides a comprehensive and valuable summary of MDS/AML rates observed in PARPi maintenance studies (including ARIEL3). Dr. Armstrong hypothesizes that the rate of MDS/AML may contribute to the overall survival outcomes observed in these recurrent-setting PARPi maintenance trials, which failed to demonstrate the same level of benefit as seen for PFS outcomes. We agree that additional information is needed for patients diagnosed with MDS/AML, although it can be argued that the low overall occurrence of such events is less likely to exert an impact on OS outcomes relative to other factors, including cross over to PARPi therapy, multiple lines of therapy in patients with prolonged survival, and possible cross-resistant mechanisms of action between PARPi and platinum therapy. AML and MDS associated with PARP inhibitor treatment of ovarian cancerGynecologic OncologyPreviewI read with interest and concern the publication of O'Malley et al. on exceptional responders in the ARIEL3 study of rucaparib maintenance [1]. Of particular note was the information on therapy related myeloid neoplasia (TMN), particularly in light of recent changes in the regulatory landscape for PARP inhibitors in the treatment of ovarian cancer. TMN reporting traditionally includes the hematologic malignancies myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clonal hematopoiesis (CH), the accumulation of somatic mutations in hematopoietic stem cells and a precursor to myeloid malignancies, is not easily measured and is not routinely reported. Full-Text PDF
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