Attribution of value for combination immune checkpoint inhibitors in non-small cell lung cancer

Immunotherapy represents a significant breakthrough in the treatment of cancer, including non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) are used in combination with other treatments to provide clinically meaningful outcomes for NSCLC patients. However, there are distinct mechanisms of action that an ICI may provide such clinically meaningful benefits. We focused on the valuation of ICIs when used in combination with existing treatments for NSCLC, by addressing the following questions: (1) do combination ICIs improve clinical outcomes due to independent, rather than synergistic or additive drug action; and (2) how should we attribute value to the constituent parts of combination ICIs? To address these questions, we reviewed the United States Food and Drug Administration (FDA) drug database and Clinicaltrials.gov from January 1, 2012, until June 1, 2022, to identify approved indications of combination ICIs in NSCLC. For valuation methods, a separate search was conducted in PubMed, health technology assessment databases, and grey literature to identify published value assessment or attribution methods, specifically in the context of combination (cancer) treatments. As of June 1, 2022, the FDA approved eight combination ICI indications for NSCLC. The underlying mechanisms for the improved clinical benefits of these ICI therapies are not well studied. The superiority of combination ICI therapies compared to monotherapy in multiple indications does not indicate whether synergy or additivity is involved, or necessary. Policy statement: We encourage further research on the development of value attribution framework methods for combination therapies to quantify their added health benefits and economic value in the future. Given the valuation challenges of combination ICIs, their mechanism of action poses significant uncertainty and requires further clinical investigation to address whether synergy or additivity is existent.