Background: As caregivers (CGs) may play a key role in helping patients manage clinical and non-clinical aspects of treatment for metastatic non-small cell lung cancer (mNSCLC), it is useful to understand their perceptions of the benefits and risks of currently available therapies and how they value the different efficacy and toxicity profiles of novel therapies. This study quantified CG preferences for attributes associated with chemotherapy and immunotherapy, alone or in combination, for mNSCLC and the economic burden of treatment. Methods: CGs of patients with mNSCLC completed an online, cross-sectional survey assessing preferences via a discrete choice experiment (DCE), which was designed based on qualitative research with CGs and pilot tested. In the DCE, 2 hypothetical treatment profiles, varying on 7 attributes (Table 1) were presented side-by-side in a series of tasks, and CGs chose their preferred option. Hierarchical Bayesian modeling was used to estimate preference weights for each attribute level. Additional questions inquired about economic burden. Results: CGs (N=166; 67% female) provided care a mean of 36 hours per week, usually for a spouse (65%). Almost half were currently employed. Increasing OS from 11 to 30 months was most important; it was 5.5% more important than decreasing the risk of a serious adverse event that may lead to hospitalization (Grade 3/4 AE) from 70% to 18%. These attributes were over twice as important as the other attributes (Figure 1). To accept an increase in risk of a Grade 3/4 AE from 18% to 70%, all grades nausea from 10% to 69%, skin rash from 12% to 22%, and pneumonitis from <1% to 8%, OS would need to increase by 17, 4, 1.5, and 0.4 months, respectively. Most CGs (72%) provided financial support; 30% incurred out-of-pocket (OOP) costs for travel to treatment, and 25% reported unpaid leave from work. Among CGs who reported OOP costs, 19%, 28%, 53%, and 57% rated costs associated with cancer drugs, travel, lodging, and unpaid leave, respectively, as burdensome (rating of 4 or 5 on a 5-point scale). Conclusions: The results showed that to accept a higher toxicity risk, CGs may require up to 1.5 years of increased OS in exchange. Findings also suggest that treatment for mNSCLC poses an economic burden for most CGs in terms of both direct and indirect (e.g., unpaid leave) costs. Treatment selection in 1L mNSCLC that considers the CG role should be informed by benefits/risks of treatment, as well as cost factors.