OBJECTIVES: The objective of the study was to propose an alternative indirect comparison method and compare it to the standard method. METHODS: In the absence of head-to-head trials, the standard method for estimating indirect relative effectiveness is to obtain an indirect hazard ratio (HR) estimate using the two HRs from the comparator trials against a common 3rd one. This method, however, is only valid if the assumption of proportional hazard (PH) holds. We proposed an alternative indirect comparison method that does not depend on the PH assumption, which consists of calculating the absolute difference between treatment arms at each two-week period in drug B trial and applying this difference to the common comparator in drug A trial to generate the adjusted curve for drug B. This was done for Progression free Survival (PFS) and Overall Survival (OS) from parametric estimates throughout the observed and extrapolated periods. Trial data for cetuximab and panitumumab in 1st line treatment of wild-type KRAS metastatic colorectal cancer was used to examine the PH assumption and compared the two methods for estimating the relative treatment effect between the two agents.  RESULTS: The functional form for the PFS and OS distributions was found to be different for panitumumab versus cetuximab (Weibull shape parameter value for: PFS=1.616 versus 1.761; OS=1.314 versus 1.336, respectively). Thus, the PH assumption was violated. Panitumumab trial was set as the reference (the estimated mean PFS= 0.917 years and mean OS=2.469). Using the standard method and our proposed method, the indirectly estimated PFS and OS for cetuximab were: mean PFS 0.846 vs 0.920 years; mean OS= 2.393 versus 2.312 years, respectively. CONCLUSIONS: The standard methodology for indirect comparison allows easy execution. However, if the PH assumption is violated, alternative methods, such as the one proposed in this study, can be considered.