OBJECTIVES:  Nivolumab was the first immunotherapy to demonstrate a significant overall survival benefit versus standard of care for previously treated patients with advanced or metastatic renal cell carcinoma (RCC) in a phase III trial setting. While conclusive phase III trial evidence for the immunotherapeutic benefit of nivolumab on overall survival beyond 3 years is not yet available for RCC, phase I/II data support a clinical rationale that some nivolumab patients will achieve long-term overall survival. Such benefit has also been seen in melanoma with other immunotherapy drugs. The objective of this research is to illustrate the importance of immunotherapeutic assumptions for long-term survival estimates and the potential impact on health technology appraisal decisions. METHODS:  Alternative extrapolations of pivotal phase III (CheckMate 025) and supportive phase I (study 003) survival data for nivolumab in RCC were compared to illustrate the importance of long-term survival assumptions for value projections. RESULTS:  Long-term survival projections vary depending on dataset and model choice, and whether clinical expectations based on key evidence and rationale are incorporated. For RCC patients treated with nivolumab who survive to 3 years, projected survival for an additional 10 years is 8% using the generalized gamma model extrapolation of CheckMate 025 data, versus 46% when quantified clinical expectations are incorporated into this projection, and 42% using the Gompertz model extrapolation of study 003 data. In England, these different survival assumptions cause the incremental cost-effectiveness ratio for nivolumab versus axitinib to range from below £25,000 to over £50,000, based on list price. CONCLUSIONS:  Using clinical expert estimates to inform long-term survival projections is pertinent in the absence of long-term patient data. This approach becomes essential when the immunotherapeutic mechanism of action of a treatment and early evidence suggest a survival plateau that is not offered by other currently available treatments.