Analysis of Factors Influencing the Assessment of Metastatic Solid Oncology Products in France: Central Role of Overall Survival (OS) Results and Other Parameters

OBJECTIVES: Although OS remains the gold standard for clinical trials in oncology, observed assessment differences between products with comparable similar OS results suggest the influence of additional factors beyond OS, highlighting the need to move beyond spontaneous comparisons of OS outcomes to adequately assess the efficacy of oncology products.

METHODS: We searched for products TC opinion from 2021 treating metastatic cancers in solid oncology (reassessment & early access excluded).We then looked for factors influencing a different level and/or downgrading of appraisal regarding clinical added value (CAV) when OS results were similar.

RESULTS: Out of 39 opinions identified, 17 had either a non-significant OS or were unavailable (100% had a minor clinical added value (CAV): IV or no CAV: V). For the other opinions (22/39), OS results were available and significant, and 14/22 opinions obtained a significant level of added value (CAV III: moderate). For a gain between 0-3 months and HR=0.7-0.8: 3 opinions with CAV IV. For mOS 3-6 and HR=0.7-0.8: 1 CAV III and 2 CAV IV, HR=0.6-0.7: 4 CAV III and 2 CAV IV, HR=0.5-0.6 and <0.5: 2 CAV III. For mOS>6 months and HR=0.7-0.8: 1 CAV III, HR=0.6-0.7: 2 CAV III and 1 CAV V, HR=0.5-0.6: 1 CAV III. for mOS not reached and HR=0.6-0.7: 3 CAV III and 1 CAV 1. The reasons leading to a different or downgraded assessment (CAV IV/V) for opinions with similar OS results were: safety concern 62% and potential impact quality of life, methodological weaknesses 100% (mainly due to included population 62% or comparator 37%).

CONCLUSIONS: OS is expected by the French Transparency Commission in oncology, but its value can vary according to clinical pertinence, need in the indication and the quality of the study's methodology. Other qualitative parameters may also have an influence, such as expert opinion or patient contributions.