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Impact of BMI on the outcome of metastatic breast cancer patients treated with everolimus: a retrospective exploratory analysis of the BALLET study.

ABSTRACT: INTRODUCTION:Reliable biomarkers of response to mTOR inhibition are yet to be identified. As mTOR is heavily implicated in cell-metabolism, we investigated the relation between BMI variation and outcomes in metastatic breast cancer (mBC) patients treated with everolimus. RESULTS:we found a linear correlation between everolimus exposure duration and BMI/weight decrease. Patients exhibiting >2 kg weight loss or >3% BMI decrease from baseline at the end of treatment (EOT) had a statistically significant improvement in PFS. Interestingly, a similar BMI/weight decrease within the first 8 weeks of therapy identified patients at higher risk of progression. PATIENTS AND METHODS:we performed a retrospective analysis of patients enrolled in the BALLET trial who progressed during the study. Primary end-point was progression-free survival (PFS). Secondary end-point was the identification of other predictors of response. CONCLUSION:A >3% weight loss at EOT is associated with better outcome in mBC patients treated with everolimus. On the contrary, a significant early weight loss represents a predictor of poor survival and could therefore be used as an early negative prognostic marker. As PI3K-inhibition also converges onto mTOR, these findings might extend to patients treated with selective PI3K inhibitors and warrant further investigation.

SUBMITTER: Corona SP

PROVIDER: S-EPMC7289535 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Impact of BMI on the outcome of metastatic breast cancer patients treated with everolimus: a retrospective exploratory analysis of the BALLET study.

Corona Silvia P SP Giudici Fabiola F Jerusalem Guy G Ciruelos Eva E Strina Carla C Sirico Marianna M Bernocchi Ottavia O Milani Manuela M Dester Martina M Ziglioli Nicoletta N Barbieri Giuseppina G Cervoni Valeria V Montemurro Filippo F Generali Daniele D

Oncotarget 20200609 23

<h4>Introduction</h4>Reliable biomarkers of response to mTOR inhibition are yet to be identified. As mTOR is heavily implicated in cell-metabolism, we investigated the relation between BMI variation and outcomes in metastatic breast cancer (mBC) patients treated with everolimus.<h4>Results</h4>we found a linear correlation between everolimus exposure duration and BMI/weight decrease. Patients exhibiting >2 kg weight loss or >3% BMI decrease from baseline at the end of treatment (EOT) had a stati ...[more]

PMID: 32577163

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Project description:BackgroundThis study investigated the incidence, radiographic patterns, and relevance to clinical outcome of everolimus-related pneumonitis (ERP) in patients with metastatic breast cancer (MBC).Materials and methodsData of patients with MBC treated with everolimus who had baseline and at least one follow-up chest computed tomography (CT) were obtained from a medical electronic database system. An independent review of the CT scans of these patients was conducted by two radiologists (NCT03730428). Log-rank and Cox proportional hazard regression analyses were used for time-to-event analyses.ResultsERP was radiographically detected in 45 of 86 patients (52.3%). In more than 80% of these patients, ERP occurred during the first 4 months of everolimus treatment. Only 14 of the 45 patients with ERP were symptomatic (31.1%). Symptoms included cough, fever, and shortness of breath. Bilateral and lower distribution of the pneumonitis was most common. In most of the cases, ground-glass opacities and reticular opacities were noticed. Elderly patients were more likely to develop ERP. Patients with ERP had significantly longer progression-free survival (PFS; 6.8 vs. 4.1 months, p = .024) and overall survival (OS; 42.8 vs. 21.3 months, p = .016). ERP was a predictor of OS improvement confirmed by multivariate Cox analysis (hazard ratio, 0.49; 95% confidence interval, 0.25-0.97; p = .040).ConclusionsERP was noted in half of the patients with MBC treated with everolimus. Our data suggested that ERP was associated with improved prognosis and may be used as a biomarker for the efficacy of everolimus in MBC. Close monitoring, prompt diagnosis, and proper treatment for ERP are essential to maintain the quality of life of patients and achieve maximum treatment benefits.Implications for practiceEverolimus-related pneumonitis (ERP) is one of the most worrying drug adverse events, especially in Asian patients. However, little has been known about the clinical and radiographic details of ERP in patients with metastatic breast cancers (MBCs) treated with everolimus. The present study investigated the clinical characteristics, radiographic patterns, and its correlation with treatment outcome in patients with MBC. ERP was identified in more than half of patients with MBC during everolimus therapy and was associated with improved outcome. Close monitoring and prompt diagnosis and appropriate treatment for ERP are critical for the preservation of patients' quality of life and achievement of maximal treatment benefits.

Project description:Background and purposeThe impact of excess body weight on prognosis after stroke is controversial. Many studies report higher survival rates in obese patients ("obesity paradox"). Recently, obesity has been linked to worse outcomes after intravenous (IV) thrombolysis, but the number and sample size of these studies were small. Here, we aimed to assess the relationship between body weight and stroke outcome after IV thrombolysis in a large cohort study.MethodsIn a prospective observational multicenter study, we analyzed baseline and outcome data of 896 ischemic stroke patients who underwent IV thrombolysis. Patients were categorized according to body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obese (30-34.9 kg/m2) or severely obese (>35 kg/m2). Using uni- and multivariate modeling, we assessed the relationship of BMI with favorable outcome (defined as modified Rankin Scale 0 or 1) and mortality 3 months after stroke as well as the occurrence of symptomatic intracerebral hemorrhages (sICH). We also measured the incidence of patients that had an early neurological improvement of >40% on the National Institutes of Health Stroke Scale (NIHSS) after 24 hours.ResultsAmong 896 patients, 321 were normal weight (35.8%), 22 underweight (2.5%), 378 overweight (42.2%), 123 obese (13.7%) and 52 severely obese (5.8%). Three-month mortality was comparable in obese vs. non-obese patients (8.1% vs. 8.3%) and did not differ significantly among different BMI groups. This was also true for favorable clinical outcome, risk of sICH and early neurological improvement on NIHSS at 24 hours. These results remained unchanged after adjusting for potential confounding factors in the multivariate analyses.ConclusionBMI was not related to clinical outcomes in stroke patients treated with IVT. Our data suggest that the current weight-adapted dosage scheme of IV alteplase is appropriate for different body weight groups, and challenge the existence of the obesity paradox after stroke.

Project description:BackgroundEverolimus, 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.MethodsPatients 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.ResultsIn 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).ConclusionsOur 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.

Dataset Information

Impact of BMI on the outcome of metastatic breast cancer patients treated with everolimus: a retrospective exploratory analysis of the BALLET study.

Publications

Impact of BMI on the outcome of metastatic breast cancer patients treated with everolimus: a retrospective exploratory analysis of the BALLET study.

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