Efficacy and safety of everolimus in Chinese metastatic HR positive, HER2 negative breast cancer patients: a real-world retrospective study

Gong, Chengcheng; Zhao, Yannan; Wang, Biyun; Hu, Xichun; Wang, Zhonghua; Zhang, Jian; Zhang, Sheng

doi:10.18632/oncotarget.16336

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…Additionally, the AEs profile in this study was similar to that of previous studies [5–7, 22]. Consistent with previous reports, stomatitis was the most frequent treatment-related adverse event.…”

Section: Discussionsupporting

confidence: 91%

“…We also did not find any difference in outcomes between patients who received endocrine drugs to which they acquired primary resistance in previous treatments and patients who received endocrine drugs to which they acquired nonprimary resistance ( p > 0.05). A real-world retrospective study performed in China also found results similar to ours [22].…”

Section: Discussionsupporting

confidence: 88%

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Everolimus in hormone receptor-positive metastatic breast cancer: PIK3CA mutation H1047R was a potential efficacy biomarker in a retrospective study

Liu

et al. 2019

BMC Cancer

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Background Everolimus, an inhibitor of mammalian target of rapamycin ( mTOR ), has been shown to increase the efficacy of endocrine therapies in hormone receptor (HR)-positive metastatic breast cancer. However, because breast cancer is a highly heterogeneous disease, the responses of different patients to everolimus may vary. Therefore, we performed this study to better select patients who will benefit most from or be resistant to everolimus. Methods Patients with HR-positive breast cancer who were treated with everolimus at the Cancer Hospital, Chinese Academy of Medical Sciences from February 2014 to March 2017 were enrolled in the present study. Mutations in ctDNA were assayed in 1021 tumor-related genes via gene panel target capture-based next-generation sequencing. Results In total, 120 patients with metastatic breast cancer who were treated with everolimus were enrolled in the present study. The median progression-free survival (PFS) of all patients was 5.1 months (95% confidence interval [CI] 3.9–6.3 months). No difference in survival was observed between patients who received endocrine drugs used in previous treatment regimens and patients who did not receive these drugs (median PFS 5.2 and 5.1 months, respectively, p > 0.05). Additionally, we did not find any difference in outcomes between patients who had primary resistance to previously used endocrine drugs and patients who had nonprimary resistance to previous treatments ( p > 0.05). Multivariate analysis showed that < 3 metastatic sites, < 2 lines of previous endocrine therapy, < 2 lines of previous chemotherapy, and treatment with everolimus combined with fulvestrant were associated with improved survival ( p < 0.05). Sixteen patients underwent ctDNA analysis before everolimus treatment. The frequency of PIK3CA gene mutations was 62.5%, and H1047R was the most frequently detected mutation. Patients with the PIK3CA/ H1047R mutation had longer PFS than patients with wild-type or other mutant forms of PIK3CA , and the median PFS in these two groups of patients was 8.8 and 4.1 months, respectively ( p < 0.05). Conclusions Our data suggest that patients who receive more lines of chemotherapy or endocrine therapy are less likely to benefit from everolimus. For everolimus combination therapy, we can even select endocrine drugs that gave rise to primary resistance in previous treatments. Additionally, the PIK3CA/ H1047R mutation may be a potential biomarker of sensitivity to everolimus. Electronic supplementary material The online version of this article (10.1186/s12885-019-5668-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

Everolimus in hormone receptor-positive metastatic breast cancer: PIK3CA mutation H1047R was a potential efficacy biomarker in a retrospective study

Liu

et al. 2019

BMC Cancer

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“…An example is the everolimus, an mTOR inhibitor approved by the FDA for the treatment of many types of cancer, including kidney cancer and some neuroendocrine tumors. Association of everolimus with endocrine therapy showed a good option for HER-2- and ER+ metastatic breast cancer [ 134 ]. In renal cell carcinoma it was observed that everolimus associated with other drugs, as levantinib, cabozantinib and nivolumab, has a better antitumoral effect than everolimus alone [ 135 ].…”

Section: Signalling Pathways Downstream Receptor Tyrosine Kinasesmentioning

confidence: 99%

Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: the current arsenal of inhibitors

2018

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Searching for targets that allow pharmacological inhibition of cell proliferation in over-proliferative states, such as cancer, leads us to finely understand the complex mechanisms orchestrating the perfect control of mitosis number, frequency and pace as well as the molecular arrangements that induce cells to enter functional quiescence and brings them back to cycling in specific conditions. Although the mechanisms regulating cell proliferation have been described several years ago, never before has so much light been shed over this machinery as during the last decade when therapy targets have been explored and molecules, either synthetic or in the form of antibodies with the potential of becoming cancer drugs were produced and adjusted for specific binding and function. Proteins containing tyrosine kinase domains, either membrane receptors or cytoplasmic molecules, plus the ones activated by those in downstream pathways, having tyrosine kinase domains or not, such as RAS which is a GTPase and serine/threonine kinases such as RAF, play crucial role in conducting proliferation information from cell surroundings to the nucleus where gene expression takes place. Tyrosine kinases phosphorylate tyrosine residues in an activating mode and are found in important growth factor receptors, such as for ligands from families collectively known as VEGF, PDGF and EGF, to name a few and in intracellular downstream molecules. They all play important roles in normal physiology and are commonly found mutated or overexpressed in neoplastic states. Our objective here is to present such kinases as druggable targets for cancer therapy, highlighting the ones for which the pharmacological arsenal is available, discussing specificity, resistance mechanisms and treatment alternatives in cases of resistance, plus listing potential targets that have not been successfully worked yet.

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“…Recently, the combination of everolimus and endocrine therapy has also been proven to be effective in the Chinese population, and the safety profile was similar to that in previous studies, with a lower incidence of grade 3–4 adverse events. 25 The phase III Breast Cancer Trials of OraL EveROlimus-3 (BOLERO-3), 21 which compared the effect of everolimus plus trastuzumab and vinorelbine with that of placebo plus trastuzumab and vinorelbine in patients with HER2-positive and trastuzumab-resistant advanced breast cancer who had received taxane therapy, concluded that everolimus significantly prolonged mPFS (7.00 months vs . 5.78 months; P = 0.0067).…”

Section: Pi3k/akt/mtor Pathway Inhibitorsmentioning

confidence: 99%

Progress in targeted therapy for breast cancer

Zhu

Yuan

2018

Chronic Diseases and Translational Medicine

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Breast cancer is a multistep, multifactorial, and heterogeneous disease. Significant transformations have occurred in the systemic management of breast cancer in the past decade. Due to the further understanding of pathogenesis, scientists have found plenty of signaling pathways and correspondingly therapeutic targets in breast cancer, such as hormone receptor, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), phosphoinositide-3-kinase (PI3K), v-akt murine thymoma viral oncogene homolog (AKT), mechanistic target of rapamycin (mTOR), cyclin-dependent kinase 4/6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP), and programmed death-1 (PD-1). Targeted therapy, which optimizes the accuracy of antitumor activity and minimizes toxicity to normal tissues, plays a crucial role in breast cancer treatment in the era of precision medicine. In this review, we aimed to summarize the latest developments in targeted therapy for breast cancer and discuss the existing problems.

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Efficacy and safety of everolimus in Chinese metastatic HR positive, HER2 negative breast cancer patients: a real-world retrospective study

Cited by 11 publications

References 34 publications

Everolimus in hormone receptor-positive metastatic breast cancer: PIK3CA mutation H1047R was a potential efficacy biomarker in a retrospective study

Everolimus in hormone receptor-positive metastatic breast cancer: PIK3CA mutation H1047R was a potential efficacy biomarker in a retrospective study

Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: the current arsenal of inhibitors

Progress in targeted therapy for breast cancer

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