Bypassing the evidence pathway: World-first tumour-agnostic reimbursement for dual immunotherapy

For the first time, an anti-cancer therapy - the combination of nivolumab and ipilimumab - has been recommended for tumour-agnostic reimbursement without biomarker requirements. In a bold step, Australia's Pharmaceutical Benefits Advisory Committee (PBAC) proposes that prescribing should be guided by "clinical judgement" for undefined "immunotherapy-sensitive" advanced or metastatic cancers. This decision raises several concerns. Firstly, tumour-agnostic approvals have typically depended on molecular markers such as MSI-H/dMMR and high tumour mutational burden (TMB), which predict substantially higher response rates. In contrast, activity in biomarker-low populations is overall limited. Second, immune-related toxicities, including their potential for long-lasting impact on quality of life, are rather unique to immunotherapy, and particularly significant with dual checkpoint inhibition. Third, a broad tumour-agnostic listing risks incentivising use in tumour types even where evidence is negative, potentially displacing effective therapies and reducing enrolment in clinical trials. Collectively, such authorisation would increase unwarranted variation in clinical practice, expose many patients to serious adverse events without benefit, and undermine the evidence generation needed for sustainable reimbursement. We recommend managed access programs that define explicit eligibility criteria, use biomarker-based patient selection when supported by evidence, and implement structured prospective registries to systematically track patient outcomes, adverse events, and cost-effectiveness. This approach would ensure that data collected can directly inform future evidence-based reimbursement and coverage decisions.