OBJECTIVES: Increasing oncology drug prices have led to several value-based framework initiatives in the US. To understand the key determinants impacting decision-making, a hypothetical oncology treatment was evaluated using the American Society of Clinical Oncology (ASCO) and Institute for Clinical and Economic Review (ICER) frameworks.  METHODS: The ASCO adjuvant setting value framework estimates the net health benefit (NHB) of an oncology drug using trial-based clinical benefit and toxicity. ICER’s framework evaluates the “Care Value” in the context of clinical effectiveness, incremental cost, benefits/disadvantages, and other contextual factors. Care value is then benchmarked to determine value to a health system. A hypothetical treatment was compared to best standard care (BSC) for a population with 0.5% disease prevalence. Treatment was assumed to reduce risk by 5% (overall survival [OS]) and 10% (progression-free survival [PFS]), cost 10% more than BSC, improve tolerability, and reduce administration burden. NHB was calculated using the ASCO framework. Incremental cost/quality-adjusted life-year (QALY) was determined using a partitioned survival model; budget impact was estimated separately using drug, administration and adverse event costs. Costs were assessed within ICER’s value-based framework using these models. Various scenarios were utilized to compare and contrast outcomes of the frameworks. RESULTS: NHB, cost/QALY gained, and budget impact were 58/100, $318,274, and ~$11 million, respectively. Changes in OS impact assessed drug value within both frameworks. The ASCO framework is sensitive to changes in tolerability while this effect was modest in the ICER framework. Substantial drug price reductions may be necessary in order to meet ICER thresholds even when maximum NHBs are present as assessed within the ASCO framework. Overall budget impact is considered in the ICER framework, but is unlikely to impact decision-making for low-prevalence diseases. CONCLUSIONS: The ASCO and ICER value frameworks may favor different types of drugs depending upon their clinical and economic profile.