How Do We Rethink Drug Assessment Models As Oncology Combination Regimens Become the Norm, Including in Early Lines of Therapy?

OBJECTIVES: This study aims to provide the authors’ perspective of the future oncology treatment paradigm, discuss associated challenges for European access, and explore implications and solutions.

METHODS: Data was collected from relevant databases (e.g., Trial Trove) and HTA reports were appraised to understand payer mentality.

RESULTS: Limited acceptance of endpoints beyond OS by European payers has resulted in innovative regimens not being launched. For instance, the nivolumab/relatlimab combination in melanoma was not launched in Germany as, despite doubling PFS, it did meet OS, the patient relevant gold standard endpoint under AMNOG. This is just one example in a series of treatments not launched due to unfavorable payer evaluations, despite improvements in other endpoints (e.g., PFS). Similar issues are expected in breast and prostate cancers, where using OS as the gold standard is punitive given patients may live for years. Moreover, amongst ongoing Phase II/III trials in these settings, only 12 out of 74 have OS as a primary endpoint (whereas most focus on PFS, response rates etc.).

CONCLUSIONS: Combination regimens (e.g., IO+IO, IO+ADC) will play an increasingly significant role in oncology treatment given potential to provide synergistic anticancer activity, address heterogeneity, overcome resistance and improve survival. As a result, combination regimens are set to supersede monotherapies, move earlier in the disease course and patients could die with, rather than from, cancer. As such, OS could become an elusive endpoint, presenting new challenges surrounding how payers reward innovation and view surrogate endpoints, given only OS is primarily valued by Western European payers. Whilst some change is being witnessed (e.g., acceptance of recurrence in adjuvant & neo-adjuvant settings), there is a need for payers to re-think their approaches and move away from predominantly rewarding OS or manufacturers will increasingly question launch potentially impacting patient access to innovative therapies.