OBJECTIVES: HTA agencies have different requirements and preferences in terms of both the models they receive and the clinical evidence that submission are based on. Our aim was to understand what could be learned about the preferences of the PBAC in Australia and NICE and the SMC in the UK specific to oncology from five selected case studies. METHODS: Five high-profile cancer drugs, namely Avastin (bevacizumab), Erbitux (cetuximab), Sprycel (dasatinib), Tykerb/Tyverb (lapatinib) and Tarceva (erlotinib) were selected as our research sample. All assessment guidance related to the five drugs by NICE, the PBAC and the SMC were reviewed to examine the rationale behind positive or negative recommendations. Based on the review, we analysed the agencies’ preferences for oncology HTA submissions. RESULTS:  Avastin has been one of the most rejected drugs among the three agencies, with the exception of PBAC’s recommendation of listing for 1st line metastatic colorectal cancer treatment on the condition of a patient access scheme. The increase to the overall drug cost by including Avastin in the treatment regimen has been the main concern with other negative factors including the inappropriate choice of comparators.Tykerb received negative recommendations from both PBAC and SMC for breast cancer due to concerns over small trial population size, robustness of efficacy evidence as well as high ICER. Between the 5 drugs, 21 HTA reviews took place, resulting in 11 positive recommendations, 10 rejections and 1 deferred decision for further price negotiation. Out of the positive recommendations, 4 were based on risk sharing arrangements. CONCLUSIONS: HTA agencies respond differently to submissions based on the same clinical dossier. Understanding in detail what the evidence preferences are of the individual agencies is crucial of the probability of reimbursement is to be maximised. This understanding should be fed into clinical development and supplementary evidence plans.