Anita Moein, Jin Y Jin, Matthew R Wright, Harvey Wong
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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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Tumor growth rate constant (K<sub>g</sub>) was found to increase with increasing baseline tumor size and in the absence of baseline endocrine sensitivity. Further, K<sub>g</sub> 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial registration: </strong>NCT02340221 Registered January 16, 2015, NCT01296555 Registered February 14, 2011.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quantitative characterization of the effects of fulvestrant alone or in combination with taselisib (PI3Kinase inhibitor) on longitudinal tumor growth in patients with estrogen receptor-positive, HER2-negative, PIK3CA-mutant, advanced or metastatic breast cancer.\",\"authors\":\"Anita Moein, Jin Y Jin, Matthew R Wright, Harvey Wong\",\"doi\":\"10.1007/s00280-024-04690-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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. 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引用次数: 0
摘要
目的：在乳腺癌病例中，雌激素受体阳性（ER +）、PIK3CA 基因突变、HER2-晚期乳腺癌是一种特别复杂的临床指征，约 40% 的 ER + /HER2- 乳腺癌存在 PIK3CA 基因突变。治疗 ER + 乳腺癌的一个重要障碍在于克服内分泌耐药性的挑战。在临床环境中，对这一适应症采取多方面的方法至关重要，不仅要探索单个疗法的有效性，还要深入研究联合疗法可能带来的治疗效果：在目前的研究中，我们建立了纵向肿瘤生长抑制（TGI）模型，以描述ER+/HER2-晚期或转移性乳腺癌绝经后女性患者在接受氟维司群单独治疗或与PI3K抑制剂他赛利西联合治疗后随着时间推移的肿瘤反应。评估了临床相关协变量对TGI指标的影响，以确定最有可能从氟维司群单药治疗或与他赛利西布联合治疗中获益的患者亚群：结果发现，肿瘤生长速率常数（Kg）会随着基线肿瘤大小的增加而增加，并且在没有基线内分泌敏感性的情况下也是如此。此外，无论是氟维司群单药治疗还是与他赛利西联合治疗，在没有基线肝转移的情况下，Kg都会降低。总之，在接受他赛利西布-氟维司群联合治疗的患者中观察到了相加/潜在的协同抗肿瘤效应：这些结果对于理解联合治疗方法的治疗效果以及对这些治疗方法的个体化反应具有重要意义。最后，这项工作强调了针对癌症靶向治疗的模型药物开发的重要性：NCT02340221 注册日期：2015年1月16日；NCT01296555 注册日期：2011年2月14日。
Quantitative characterization of the effects of fulvestrant alone or in combination with taselisib (PI3Kinase inhibitor) on longitudinal tumor growth in patients with estrogen receptor-positive, HER2-negative, PIK3CA-mutant, advanced or metastatic breast cancer.
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 (Kg) was found to increase with increasing baseline tumor size and in the absence of baseline endocrine sensitivity. Further, Kg 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.
期刊介绍：
Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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