Time-to-Event Modeling for Survival Prediction of Osimertinib as the First- and Second-Line Therapy

奥希替尼作为一线和二线治疗的生存预测的时间事件模型

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Abstract

Objectives: To predict the survival rates of Osimertinib as first- and second-line therapy using time-to-event models based on literature data. Methods: Kaplan-Meier curves from randomized clinical trials were extracted after a systematic search of PubMed and Cochrane Library from their inception to 10 May 2023. Randomized clinical trials of Osimertinib reporting both first- and second-line overall survival (OS) and progression-free survival (PFS) in NSCLC patients with specific mutations, compared to earlier epidermal growth factor receptor (EGFR) inhibitors and chemotherapy. Kaplan-Meier curves of OS and PFS were extracted from published articles. A two-column raw dataset (time, survival probability) was extracted, and time-to-event outcomes (time, event) were derived using a graphic reconstructive algorithm. Data analysis was conducted from 1 June 2023 to 31 January 2024. Primary outcomes included OS and PFS for time-to-event modeling of Osimertinib as first- and second-line therapy. Results: The Weibull model, incorporating race as a covariate, best fit the first-line OS data. The log-logistic model best fit first-line PFS and second-line OS/PFS data. Based on these models, the predicted median OS for first-line and second-line treatment were 36.35 months (95% CI, 33.53-39.30 months) and 27.46 months (95% CI, 25.30-29.99 months), respectively. The predicted median PFS were 18.11 months (95% CI, 16.37-19.90 months) and 10.35 months (95% CI, 9.31-11.44 months), respectively. The predicted 3- and 5-year survival rates with first-line Osimertinib were 51% and 23%, respectively. Subgroup analysis revealed longer estimated 3- and 5-year survival rates for non-Asian patients compared to Asian patients (60% vs. 49% and 29% vs. 21%, respectively). Conclusions: The predicted survival rates from the time-to-event modeling align with the original clinical trial results, and an ethnic difference in Osimertinib efficacy was observed.

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