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

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.