Time toxicity in previously untreated metastatic or unresectable epidermal growth factor receptor-mutant non-small cell lung cancer: a clinical practice review

The approvals of first-line therapies for patients with unresectable or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (<i>EGFR</i>) mutations have drastically improved survival outcomes. However, the healthcare-related burden for these regimens, particularly the concept of time toxicity, has not been fully understood. Our analysis of time toxicity, which measures healthcare days spent for treatments and treatment-related adverse events (TRAEs) in comparison to improved survival outcomes, highlights the urgent need for further research in this area. We analyzed phase III clinical trials for untreated NSCLC: FLAURA, FLAURA2, and MARIPOSA. Trial protocols were analyzed to calculate healthcare contact days. The time cutoff for analysis was the median treatment duration in each trial's treatment arms. Time toxicity arising from TRAEs was analyzed using the National Inpatient Sample (NIS) Database (2016-2021 data). Descriptive statistics were used to calculate healthcare contact days. Amivantamab plus Lazertinib resulted in the highest time toxicity, followed by osimertinib combined with chemotherapy and osimertinib monotherapy. Based on the incidence of TRAEs, 0.13, 0.335, and 1.625 days of time toxicity were added to each trial, respectively. Overall, the estimated time toxicity was 1.03 days for the osimertinib-only group (FLAURA), 3.635 days for the osimertinib plus chemotherapy group (FLAURA2), and 6.425 days for the amivantamab plus lazertinib group (MARIPOSA). Our findings highlight a significant increase in healthcare burden with combination strategies compared to osimertinib monotherapy, underscoring the need for further research to balance time toxicity with the benefits of survival associated with each regimen.