RESUMEN
PURPOSE: This retrospective real-world study compared overall survival (OS) between patients with BRCA wild-type (BRCAwt) recurrent epithelial ovarian cancer (OC) who received niraparib second-line maintenance (2LM) versus active surveillance (AS) using target trial emulation, cloning, inverse probability of censoring weighting (IPCW) methodology to minimize immortal time bias. METHODS: Eligible patients from a United States-based, deidentified, electronic health record-derived database were diagnosed with epithelial OC (January 1, 2011-May 31, 2021), were BRCAwt, and completed second-line (2L) therapy (January 1, 2017-March 2, 2022). Patient data were cloned at index (2L last treatment date), assigned to niraparib 2LM and AS cohorts, and censored when treatment deviated from clone assignment. Follow-up was measured from index to earliest of study end (May 31, 2022), last activity, or death. Median OS (mOS) and hazard ratios were estimated from stabilized IPCW Kaplan-Meier curves and Cox regression models. RESULTS: Overall, 199 patients received niraparib 2LM, and 707 had their care managed with AS. Key characteristics were balanced across cohorts after cloning and stabilized IPCW. Median follow-up was 15.6- and 9.3-months pre-cloning. IPCW mOS was 24.1 months (95% CI: 20.9-29.5) and 18.4 months (95% CI: 15.1-22.8) in niraparib 2LM and AS cohorts, respectively (hazard ratio, 0.77; 95% CI: 0.66-0.89). CONCLUSIONS: This real-world study provides supportive evidence of an OS benefit for patients with BRCAwt recurrent OC who received 2LM niraparib monotherapy compared with those whose care was managed with AS. The analytic strategies implemented were useful in minimizing immortal time bias and measured confounding.
Asunto(s)
Indazoles , Recurrencia Local de Neoplasia , Neoplasias Ováricas , Piperidinas , Humanos , Femenino , Piperidinas/uso terapéutico , Piperidinas/administración & dosificación , Indazoles/uso terapéutico , Indazoles/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/mortalidad , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Adulto , Espera Vigilante , Estados Unidos/epidemiología , Quimioterapia de Mantención/métodos , Bases de Datos FactualesRESUMEN
OBJECTIVES: The clinical utility of maintenance therapy (MT) for patients with platinum-sensitive recurrent ovarian cancer has been validated in several clinical trials. We assessed "real-world" treatment patterns using an electronic health record (EHR) database. METHODS: A retrospective study of patients diagnosed with ovarian cancer between January 1, 2011 and July 31, 2019 was conducted using the US nationwide Flatiron Health (EHR)-derived de-identified database. Patients were included if they received second- or third-line (2 L or 3 L) platinum-based chemotherapy (PBCT). Information regarding biomarker status was obtained. RESULTS: 2292 patients with ovarian cancer received at least two lines of therapy. 222 patients completed PBCT on or after March 1, 2017 and had ≥2 months of active surveillance or received MT with poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) or bevacizumab. 46 (20%) had BRCA mutations (BRCAm), 132 (59%) had a wildtype BRCA (BRCAwt) gene, and 47 (21%) were unknown. Of patients with BRCAm, 63% received a PARPi, 17% received bevacizumab, and 20% underwent active surveillance. Of patients with BRCAwt, 40% received a PARPi, 23% received bevacizumab, and 36% underwent active surveillance. MT was more common in those with younger age and a BRCA mutation. PARPi use increased on average by 1.3% every 3 months (p = .02) with no statistically significant change in use of bevacizumab. CONCLUSIONS: In this real-world population, MT is becoming progressively more common following 2 L or 3 L PBCT regardless of biomarker status. The results provide insight into the shifting treatment patterns for patients with recurrent ovarian cancer.