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Exploring the Impact of Treatment Switching on Overall Survival from the PROfound Study in Homologous Recombination Repair (HRR)-Mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC).
Evans, Rachel; Hawkins, Neil; Dequen-O'Byrne, Pascale; McCrea, Charles; Muston, Dominic; Gresty, Christopher; Ghate, Sameer R; Fan, Lin; Hettle, Robert; Abrams, Keith R; de Bono, Johann; Hussain, Maha; Agarwal, Neeraj.
Afiliación
  • Evans R; Visible Analytics, 3 Kings Meadow, Oxford, OX2 0DP, UK. rachel.evans@visibleanalytics.co.uk.
  • Hawkins N; Visible Analytics, 3 Kings Meadow, Oxford, OX2 0DP, UK.
  • Dequen-O'Byrne P; Visible Analytics, 3 Kings Meadow, Oxford, OX2 0DP, UK.
  • McCrea C; AstraZeneca, Cambridge, UK.
  • Muston D; Center for Observational and Real-World Evidence, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Gresty C; AstraZeneca, Cambridge, UK.
  • Ghate SR; Center for Observational and Real-World Evidence, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Fan L; Center for Observational and Real-World Evidence, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Hettle R; AstraZeneca, Cambridge, UK.
  • Abrams KR; Visible Analytics, 3 Kings Meadow, Oxford, OX2 0DP, UK.
  • de Bono J; Institute of Cancer Research and Royal Marsden Hospital, London, UK.
  • Hussain M; The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Agarwal N; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Target Oncol ; 16(5): 613-623, 2021 09.
Article en En | MEDLINE | ID: mdl-34478046
BACKGROUND: In oncology trials, treatment switching from the comparator to the experimental regimen is often allowed but may lead to underestimating overall survival (OS) of an experimental therapy. OBJECTIVE: This study evaluates the impact of treatment switching from control to olaparib on OS using the final survival data from the PROfound study and compares validated adjustment methods to estimate the magnitude of OS benefit with olaparib. PATIENTS AND METHODS: The primary population from PROfound (Cohort A) was included, alongside two populations approved for treatment with olaparib by the European Medicines Agency and US Food and Drug Administration: BRCAm and Cohort A+B (excluding the PPP2R2A gene). Five methods were explored to adjust for switching: excluding or censoring patients in the control arm who receive subsequent olaparib, Rank Preserving Structural Failure Time Model (RPSFTM), Inverse Probability of Censoring Weights, and Two-Stage Estimation. RESULTS: The RPSFTM was considered the most appropriate approach for PROfound as the results were robust to sensitivity analysis testing of the common treatment effect assumption. For Cohort A, the final OS hazard ratio reduced from 0.69 (95% CI 0.5-0.97) to between 0.42 (0.18-0.90) and 0.52 (0.31-1.00) for olaparib versus control, depending on the RPSFTM selected. Median OS reduced from 14.7 months to between 11.73 and 12.63 months for control. CONCLUSIONS: The magnitude of the statistically significant (P < 0.05) survival benefit of olaparib versus control observed in Cohort A of PROfound is likely to be underestimated if adjustment for treatment switching from control to olaparib is not conducted. The RPSFTM was considered the most plausible method, although further development and validation of robust methods to estimate the magnitude of impact of treatment switching is needed.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male País/Región como asunto: America do norte Idioma: En Revista: Target Oncol Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article Pais de publicación: Francia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male País/Región como asunto: America do norte Idioma: En Revista: Target Oncol Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article Pais de publicación: Francia