Frailty, initial attrition and feasibility of novel platinum-free options for advanced non-small-cell lung cancer in the real-world setting

BACKGROUND: How frailty limits initial therapy in metastatic non-small-cell lung cancer (mNSCLC) remains poorly understood and was investigated in this study. METHODS: We retrospectively analyzed 2592 consecutive patients with mNSCLC treated between 2018-2023. RESULTS: Systemic therapy was initiated in 74% of patients with PD-L1 0-49% (n = 1306) vs. 79% with PD-L1 ≥50% (n = 507, p = 0.014), in whom availability of monoimmunotherapy reduced best supportive care (16.4%vs. 22.3%, p = 0.0002), while early death remained unchanged (ca. 4%). 70% of patients receiving mBSC were initially treatable but suffered early deterioration associated with comorbidities, metastatic burden, or protracted workup (p < 0.001). The atezolizumab Summary of Product Characteristics (SmPC) criteria, i.e. >80 years, or ECOG performance status (PS) ≥3, or comorbidities with PS ≥2 or age ≥70, were fulfilled by 38% (n = 501) and associated with 3-fold higher risk of death without therapy (230/501) compared to non-SmPC patients (p < 0.001). Under platinum, SmPC patients showed higher toxicity and shorter survival than non-SmPC patients, which for a platinum dose ratio ≤60% across 4 cycles (9% of 1306) resembled that with single-agent chemotherapy (median 5.1 months). SmPC criteria correlated with platinum use stronger than comorbidity scores, but predictability for individual patients remained modest (AUC 0.71, p < 0.001). CONCLUSIONS: The high pretherapeutic attrition of 26% in mNSCLC improved with availability of monoimmunotherapy, but requires more efficient, faster patient workflows for further mitigation. Adoption of the SmPC criteria could support identification of patients at higher risk for mBSC or potential platinum overtreatment to enhance utilization of novel platinum-free first-line options.