We developed a checklist capturing multi-stakeholder perspectives on assessing the long-term clinical benefit of cancer immunotherapy. The checklist used input from multi-country advisory panels into the key issues to be addressed by both manufactures and payers.

Immunotherapy represents a significant breakthrough in the treatment of cancer across multiple tumor types and patient populations. Immunotherapies differ from traditional cancer therapies as they do not target cancer directly, but instead target the body’s immune system. This changes the mechanism of survival in treated patients, as well as the shape of the survival curve and smoothing estimators of the hazard function. This is the effect known as the ‘plateau’ or ‘tail of the curve’: the flattening of the overall survival Kaplan-Meier curve typically seen after 2 years of follow-up. How best to demonstrate and convey the longer-term health gains of immunotherapies at both regulatory and HTA filing offer is widely contested and impacts access for patients worldwide.

In our research to be presented, an international, multi-stakeholder steering committee was formed comprising 9 experts: payers, economists, and clinicians from the US, UK, France, Italy, and Sweden. Following a review of published literature and technology assessments, we identified key issues and challenges in measuring the long-term clinical benefit specific to cancer immunotherapy. Double-blinded, country-level, multi-stakeholder panels were then convened in the US, UK, France, Germany, and Sweden to refine the key issues and how to address them.

The challenges identified relate to three areas (1) mechanism of action (underlying biology, pseudo progression); (2) limited data at launch (immature overall survival, response, surrogate endpoints); and (3) the analytic methodology (non-proportional hazards and model structure, the plateau in the survival curve, heterogeneity in treatment effect and patient outcomes). To focus evidence generation on addressing those issues systematically, we developed a checklist that manufacturers can use to produce structured, multi-stakeholder evidence that addresses the key challenges for HTA of cancer immunotherapies. Applying a consistent approach to evidence generation, HTA submissions and assessments, will help to improve estimation and consistency, and reduce uncertainty, around the long-term clinical benefit of cancer immunotherapies.

All work relating to the development of the source guidance document and current position paper was funded by Bristol-Myers Squibb. The sponsor was not involved in the analysis or interpretation of the guidance generated.