The rapid development of oncology treatments in recent decades results in a significant increase in the number of cancer survivors. One of the most serious events experienced by this growing and heterogeneous population is the diagnosis of a second primary malignancy (SPM). Among various risk factors for SPM, e.g. cancer treatments, environmental exposures, genetic susceptibility, and simply longer survival etc., treatment-associated risks has brought increasingly more attention, especially in a regulatory setting. In this presentation, a time-to-event endpoint SPM-free survival, which denotes the time of being alive without SPM after using a treatment, is proposed to assess the benefit-risk profile of a particular treatment that may potentially cause SPMs. Simulations and clinical data are used to examine the performance of this endpoint in different scenarios. Challenges of the analysis, such as SPMs being rare events and requiring long-term follow-up, are discussed.