Presentation (CTI)

OBJECTIVES: Treatment effect modifiers are important for health technology assessment, especially when there is a need to use indirect treatment comparisons to infer relative benefits. There are methods and guidelines that suggest what is necessary to show a treatment effect modification (TEM). However, it is still unclear what evidence is sufficient to overrule a TEM perception. This study evaluates an analytical approach to assess the absence of TEM, using as an example the impact of PIK3CA mutation status in CDK4/6is treatment effect when added to fulvestrant.
METHODS: A systematic literature review was conducted to identify randomised control trials assessing CDK4/6is + fulvestrant vs fulvestrant in HR+,HER2- mBC that reported data on patients with a tumor that has PIK3CA mutations. Leveraging the Same Weights Across Different Analysis (SWADA) method, a contrast-based interaction meta-analysis utilizing the Ratio of Hazard Ratios (RHR) and 95% CI was applied to synthesize treatment effect consistency in mutated and wild type subgroups in progression free survival (PFS) and overall survival (OS).
RESULTS: The literature review identified three relevant studies: PALOMA-3, MONARCH-2, and MONALEESA-3. The pooled RHR of PIK3CA mutated versus wild type subgroups for PFS was 1.08 (95% CI: 0.78-1.48), whereas the OS RHR of PIK3CA mutated versus wild type subgroups was 0.97 (95% CI: 0.74-1.29). No cross-trial heterogeneity was observed and the direction of the interaction effect was not consistent across the two endpoints.
CONCLUSIONS: The presence of PIK3CA mutation is a proven poor prognostic factor for mBC patients, which requires the use of pathway targeted therapies. Our results suggest that the presence of the said mutation likely does not have an impact on the relative treatment effect of CDK4/6is+fulvestrant vs fulvestrant. SWADA approach used in this analysis provides an aggregation bias-free approach for assessing TEM.