AI Article Synopsis
- ER+ HER2- breast cancer often has PIK3CA mutations, complicating treatment due to endocrine resistance, necessitating a combination therapy approach.
- The study developed tumor growth inhibition models to analyze treatment responses in postmenopausal women receiving either fulvestrant alone or with taselisib, aiming to identify which patient subsets benefit most from these therapies.
- Results indicated that larger tumor size and lack of endocrine sensitivity correlate with increased tumor growth, while the combination treatment showed promising anti-tumor effects, underscoring the need for personalized treatment plans and model-informed drug development.
Article Abstract
Purpose: Among cases of breast cancer, estrogen receptor-positive (ER +), PIK3CA-mutant, HER2- advanced breast cancer stands as a particularly complex clinical indication where approximately 40% of ER + /HER2- breast carcinomas present mutations in the PIK3CA gene. A significant hurdle in treating ER + breast cancer lies in surmounting the challenges of endocrine resistance. In the clinical setting, a multifaceted approach is essential for this indication, one that not only explores the effectiveness of individual treatments but also delves into the potential gains in therapeutic outcome from combination therapies.
Methods: In the current study, longitudinal tumor growth inhibition (TGI) models were developed to characterize tumor response over time in postmenopausal women with ER + /HER2- advanced or metastatic breast cancer undergoing treatment with fulvestrant alone or in combination with the PI3K inhibitor, taselisib. Impact of clinically relevant covariates on TGI metrics was assessed to identify patient subsets most likely to benefit from treatment with fulvestrant monotherapy or combination with taselisib.
Results: Tumor growth rate constant (K) was found to increase with increasing baseline tumor size and in the absence of baseline endocrine sensitivity. Further, K decreased in the absence of baseline liver metastases both in fulvestrant monotherapy and combination therapy with taselisib. Overall, additive/potentially synergistic anti-tumor effects were observed in patients treated with the taselisib-fulvestrant combination.
Conclusion: These results have important implications for understanding the therapeutic impact of combination treatment approaches and individualized responses to these treatments. Finally, this work, emphasizes the importance of model informed drug development for targeted cancer therapy.
Clinical Trial Registration: NCT02340221 Registered January 16, 2015, NCT01296555 Registered February 14, 2011.
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| http://dx.doi.org/10.1007/s00280-024-04690-4 | DOI Listing |
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