The Ohio State University, Columbus, OH
David M. O'Malley , Rebecca Christian Arend , Naufil Alam , Ozan Ozgoren , Kimmie K. McLaurin , Grainne H. Long , Susana N. Banerjee
Background: Tolerability is a key consideration when selecting a PARP inhibitor (PARPi) for ovarian cancer (OC). Here we expand on earlier work (Arend et al 2021) to further characterize real-world tolerability and dose modifications in US patients (pts) with OC receiving PARPi therapy. Methods: A retrospective cohort of OC pts starting olaparib (ola), niraparib (nir) or rucaparib (ruc) between Jan 2017 and Dec 2020 was identified from MarketScan® Commercial/Medicare Supplemental databases, increasing the period covered and number of pts included vs our previous analysis. Pts were followed up from first PARPi prescription (index) for ≥30 days until end of study period, disenrollment or death; baseline was 6 months pre-index. Clinical events of interest (CEIs; acute myeloid leukemia/myelodysplastic syndromes, anemia, leukopenia/neutropenia, thrombocytopenia, acute kidney injury, arthralgia, constipation, diarrhea, nausea, vomiting, dermatitis/rash/photosensitivity, fatigue, hypertension, infection, insomnia, pneumonitis, transaminitis) were identified via ICD-9/10 codes. Multivariable Cox regression compared the likelihood of CEIs, dose modifications and hospitalizations between PARPis, adjusting for baseline CEI, Charlson Comorbidity Index score, prior bevacizumab and cancer-related surgery. Persistence was defined as no PARPi treatment gaps of >90 days in pts with ≥6 months’ continuous enrollment. Results: Overall, 637, 538 and 227 pts received ola, nir and ruc, respectively (median [IQR] follow-up 10.5 [13.4] months). Baseline characteristics were similar across groups. The proportion of pts initiating PARPi at the highest indicated dose was 89.2%, 57.6% and 89.9% for ola, nir and ruc, respectively; 22.6%, 34.8% and 28.6%, respectively, required dose decreases. The likelihood of experiencing CEIs varied across the PARPis after adjusting for a priori confounders as shown in the table. Persistence with index PARPi was higher with ola (83.4%) vs nir (73.3%; P<0.001) and similar vs ruc (80.2%; P>0.05). Among all pts, mean time to non-persistence was shorter with nir vs ola and ruc (6.4 vs 7.9 and 7.6 months, respectively; both P<0.05). CEIs by PARPi dose and calendar year will also be presented. Conclusions: This is the largest real-world comparison of PARPi use in OC pts reported to date. It supports differences between PARPis in persistence with therapy and risk of experiencing a CEI, even after adjusting for confounders.
Adjusted HR (95% CI) | Nir vs ola | Ruc vs ola | Nir vs ruc |
---|---|---|---|
Any CEI | 1.34 (1.19–1.52)* | 1.13 (0.96–1.33) | 1.19 (1.01–1.40)‡ |
Any hematologic CEI | 1.51 (1.30–1.77)* | 1.18 (0.96–1.45) | 1.28 (1.05–1.57)‡ |
Any non-hematologic CEI | 1.27 (1.12–1.44)* | 1.21 (1.03–1.43)‡ | 1.05 (0.89–1.23) |
All-cause inpatient hospital admission | 1.46 (1.15–1.84)† | 1.38 (1.03–1.86)‡ | 1.05 (0.79–1.40) |
Time to PARPi discontinuation | 1.73 (1.47–2.02)* | 1.35 (1.09–1.66)† | 1.28 (1.05–1.57)‡ |
*P<0.001; †P<0.01; ‡P<0.05.
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Abstract Disclosures
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