Precision Medicine in Focus: Optimizing Biomarker-Driven Treatment Strategies in HR+/HER2– P13KCA-mutant Metastatic Breast Cancer - Episode 2
Panelists discuss how the INAVO120 trial’s secondary end point showing delayed time to chemotherapy from 12 to 36 months with the triplet combination provides compelling quality-of-life benefits for patients while acknowledging the challenges of determining optimal treatment sequencing after progression on this regimen.
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Timothy J. Pluard, MD, emphasized that INAVO120 enrolled a high-risk population with endocrine resistance, defined by relapsing on or within 2 years of completing endocrine therapy. This patient population historically performs poorly with standard therapies, making the combination approach particularly valuable. The trade-off between up-front combination therapy vs sequential treatment requires careful consideration of increased toxicity against potential back-end benefits, with the overall survival data supporting the combination approach in this specific population.
A particularly compelling secondary end point was the dramatic extension in time to chemotherapy, increasing from 12 months in the placebo group to 36 months in the triplet combination arm. This 24-month delay in chemotherapy initiation has profound quality-of-life implications for patients with metastatic breast cancer, as endocrine-based therapies are generally better tolerated than cytotoxic treatments. The time to chemotherapy end point provides both efficacy evidence and a meaningful discussion point for patient counseling about treatment benefits.
The significant delay in chemotherapy progression demonstrates the triplet combination’s ability to maintain disease control with less toxic therapies for extended periods. This finding supports up-front use of the inavolisib combination in appropriate patients, particularly those with endocrine-resistant disease who may have limited opportunities for subsequent hormonal therapy lines. These data suggest that early intervention with targeted combinations can meaningfully extend the hormonal therapy treatment window, potentially improving both quantity and quality of life for patients with PIK3CA-mutated metastatic breast cancer.