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Therapy optimization remains an important challenge in the treatment of advanced non‐small cell lung cancer (NSCLC). We investigated tumor size (sum of the longest diameters (SLD) of target lesions) and neutrophil‐to‐lymphocyte ratio (NLR) as longitudinal biomarkers for survival prediction. Data sets from 335 patients with NSCLC from study NCT02087423 and 202 patients with NSCLC from study NCT01693562 of durvalumab were used for model qualification and validation, respectively. Nonlinear Bayesian joint models were designed to assess the impact of longitudinal measurements of SLD and NLR on patient subgrouping (by Response Evaluation Criteria in Solid Tumors 1.1 criteria at 3 months after therapy start), long‐term survival, and precision of survival predictions. Various validation scenarios were investigated. We determined a more distinct patient subgrouping and a substantial increase in the …