A multicentre, randomised, double-blind, phase II study to evaluate the tolerability of an induction dose escalation of everolimus in patients with metastatic breast cancer (DESIREE)

Schmidt, Marcus; Lübbe, Kristina; Decker, Thomas; Thill, Marc; Bauer, L.; Müller, V.; Link, Theresa; Furlanetto, Jenny; Reinisch, Mattea; Mundhenke, Christoph; Hoffmann, Oliver; Zahn, Mark‐Oliver; Müller, Lothar; Denkert, Carsten; Mackelenbergh, Marion van; Fasching, Peter A.; Burchardi, Nicole; Nekljudova, Valentina; Loibl, S.

doi:10.1016/j.esmoop.2022.100601

Cited by 7 publications

(6 citation statements)

References 30 publications

(33 reference statements)

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“…An alternative to reduce the incidence of stomatitis is the stepwise dose escalation of EVE used in the randomized DESIREE trial. 33 Of note, in the BOLERO-2 study, where patients did not receive prophylaxis for stomatitis, the incidence of grade ≥2 stomatitis was 30% and grade 3/4 stomatitis was 8%. 13 Taken together, these results highlight the importance of prophylactic measures for stomatitis management, which in turn may help in further improving the patients' QoL.…”

Section: Discussionmentioning

confidence: 99%

“…Patients in the SWISH trial used prophylactic dexamethasone mouthwash four times a day. An alternative to reduce the incidence of stomatitis is the stepwise dose escalation of EVE used in the randomized DESIREE trial 33 . Of note, in the BOLERO‐2 study, where patients did not receive prophylaxis for stomatitis, the incidence of grade ≥2 stomatitis was 30% and grade 3/4 stomatitis was 8% 13 .…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of everolimus plus exemestane in patients with hormone receptor‐positive, HER‐2‐negative advanced breast cancer: Results from the open‐label, multicentre, non‐interventional BRAWO study

Lüftner,

Schuetz,

Schneeweiss

et al. 2024

Intl Journal of Cancer

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BRAWO, a real‐world study, assessed the efficacy, quality of life (QoL) and safety of EVE + EXE in postmenopausal women with HR+/HER2– advanced breast cancer (ABC) in routine clinical practice. Postmenopausal women with HR+/HER2‐ABC with recurrence or progression after a NSAI were included. Primary Observation parameters included the evaluation of the effectiveness of EVE + EXE. A multivariate‐analysis using Cox proportional hazard model was built to identify predictors of progression. Overall, 2100 patients were enrolled (August 2012–December 2017); 2074 were evaluable for efficacy and safety analyses. Majority of patients (60.6%) received EVE + EXE as first (28.7%) or second‐line (31.9%) therapy. Visceral metastases were present in 54.1% patients. Median progression‐free survival (mPFS) reported as 6.6 months (95%CI: 6.3–7.0). Multivariate‐analysis in a subset of patients (n = 1837) found higher body mass index (BMI) and non‐visceral metastases to be independent predictors of favorable PFS. Patients with a BMI of 20 to <25 had a mPFS of 6.0 (95%CI: 5.4–6.4) and those with a BMI ≥30 had mPFS of 8.5 (95%CI: 6.9–9.9). 41.2% patients achieved stable disease and 7.3% partial response. No major changes were observed QoL; 86.4% patients received stomatitis prophylaxis and 41.4% experienced EVE related AEs of stomatitis, mainly low grade. AEs occurred in 91.2% of patients, of which stomatitis (42.6%) and fatigue (19.8%) were most frequent. The BRAWO study provides real‐world evidence of efficacy and safety of EVE + EXE in patients with HR+, HER2− ABC. A high BMI and the absence of visceral metastases were independent predictors of PFS in this cohort of patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of everolimus plus exemestane in patients with hormone receptor‐positive, HER‐2‐negative advanced breast cancer: Results from the open‐label, multicentre, non‐interventional BRAWO study

Lüftner,

Schuetz,

Schneeweiss

et al. 2024

Intl Journal of Cancer

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“…For instance, patient weight variations, performance status, or LDH levels at the time of metastatic disease diagnosis or at each treatment line appeared to be scarcely collected in electronic medical records and are consequently not exploitable. Furthermore, the potential toxicity of everolimus needs to be taken into account, as in this series the treatment was discontinued in 26.6% of cases owing to adverse events, although it might be mitigated by individual dose escalation [28]. Consequently, patient selection by oncologists, according to individual risk-benefit balance, may favor the fittest, which could have an influence on overall survival.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Results with Everolimus in Advanced Hormone Receptor Positive Breast Cancer in a Multicenter National Real-World Observational Study

François-Martin

Lardy-Cléaud

Pistilli

et al. 2023

Cancers

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Everolimus is the first oral targeted therapy widely used in advanced HR + / HER2− breast cancer. We sought to evaluate the impact of everolimus-based therapy on overall survival in the ESME-MBC database, a national metastatic breast cancer cohort that collects retrospective data using clinical trial-like methodology including quality assessments. We compared 1693 patients having received everolimus to 5928 patients not exposed to everolimus in the same period. Overall survival was evaluated according to treatment line, and a propensity score with the inverse probability of treatment weighting method was built to adjust for differences between groups. Crude and landmark overall survival analyses were all compatible with a benefit from everolimus-based therapy. Adjusted hazard ratios for overall survival were 0.34 (95% CI: 0.16–0.72, p = 0.0054), 0.34 (95% CI: 0.22–0.52, p < 0.0001), and 0.23 (95% CI: 0.14–0.36, p < 0.0001) for patients treated with everolimus in line 1, 2, and 3 and beyond, respectively. No clinically relevant benefit on progression-free survival was observed. Causes for everolimus discontinuation were progressive disease (56.2%), adverse events (27.7%), and other miscellaneous reasons. Despite the limitations inherent to such retrospective studies, these results suggest that adding everolimus-based therapy to the therapeutic sequences in patients with advanced HR+/HER2− breast cancer may favorably affect overall survival.

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“…For small molecule kinase inhibitors, dose escalation is indeed one of the methods to optimize administration strategy. The DESIREE prospective trial reported that the use of a stepwise dose-escalation schedule of everolimus (2.5 mg week 1 increased by 2.5 mg per week to 10 mg) could significantly reduce the incidence of high-grade stomatitis in patients with hormone receptor (HR) + /human epidermal growth factor receptor 2 (HER2) – metastatic breast cancer ( 51 ). Escalation of sunitinib dosing (12.5 mg steps) in patients with metastatic renal cell cancer, based on tolerable toxicity, has been shown to be safe and improve outcome ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Assessing the effectiveness and safety of surufatinib versus everolimus or sunitinib in advanced neuroendocrine neoplasms: insights from a real-world, retrospective cohort study using propensity score and inverse probability treatment weighting analysis

Zhu,

Ye,

She

et al. 2024

J Gastrointest Oncol

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Background While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons in a real-world setting remain unexplored. This gap highlights the clinical need to understand their comparative effectiveness and safety within the diverse Chinese population. Addressing this, our study provides insights into the real-world performance of these therapies, aiming to inform treatment selection and improve patient outcomes. Methods A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs treated with surufatinib, sunitinib, or everolimus between July 2020 and April 2023. Eligibility criteria focused on histologically confirmed, locally advanced, unresectable, or metastatic NENs, with patients having received at least one month of targeted therapy. We employed inverse probability weighting (IPW) with the propensity score (PS) matching to adjust for the bias of baseline characteristics. The assessment of covariates included age, sex, performance status, primary tumor site, functional status, genetic mutations, tumor differentiation, Ki67 index, tumor grade, metastasis site, and previous therapies. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results The study enrolled 123, 56, and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib, and everolimus, respectively. Before adjusting for confounding factors, surufatinib was used less frequently as a first-line treatment compared to sunitinib and everolimus in pancreatic NENs (pNENs) (11.1% vs. 22.1%, P=0.057). Significant differences were noted in prior treatments and tumor characteristics between surufatinib and everolimus groups in extrapancreatic NENs (epNENs) (P<0.05). Post-IPW, these disparities were resolved (P>0.05). Surufatinib demonstrated superior median PFS (mPFS) in both pancreatic [8.30 vs. 6.33 months, hazard ratio (HR) 0.592, P<0.001] and epNENs (8.73 vs. 3.70 months, HR 0.608, P<0.001) compared to everolimus or sunitinib. Notably, male gender (HR 1.75, P=0.001), functional status (HR 2.09, P=0.01), Ki67 index >20% (HR 12.7, P=0.004), previous somatostatin analogue (SSA) treatment (HR 1.73, P=0.001), germline mutation (HR 5.62, P<0.001), poor differentiation (HR 7.45, P<0.001), liver metastasis (HR 1.72, P=0.001) and multiple treatment lines (HR 1.62 for 2 nd line, P=0.04; HR 1.88 for ≥3 rd line, P=0.01) were identified as negative prognostic factors for PFS. Conversely, dose adjustment (HR 0.63, P=0.009) and treatment with surufatinib (HR 0.58 for pNEN, P<0.001; HR 0.62 for epNEN, P=0.002) were correlated with longer PFS. ...

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A multicentre, randomised, double-blind, phase II study to evaluate the tolerability of an induction dose escalation of everolimus in patients with metastatic breast cancer (DESIREE)

Cited by 7 publications

References 30 publications

Efficacy and safety of everolimus plus exemestane in patients with hormone receptor‐positive, HER‐2‐negative advanced breast cancer: Results from the open‐label, multicentre, non‐interventional BRAWO study

Efficacy and safety of everolimus plus exemestane in patients with hormone receptor‐positive, HER‐2‐negative advanced breast cancer: Results from the open‐label, multicentre, non‐interventional BRAWO study

Long-Term Results with Everolimus in Advanced Hormone Receptor Positive Breast Cancer in a Multicenter National Real-World Observational Study

Assessing the effectiveness and safety of surufatinib versus everolimus or sunitinib in advanced neuroendocrine neoplasms: insights from a real-world, retrospective cohort study using propensity score and inverse probability treatment weighting analysis

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