Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Francois-Martin H

PROVIDER: S-EPMC9954606 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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

François-Martin Hélène H Lardy-Cléaud Audrey A Pistilli Barbara B Levy Christelle C Diéras Véronique V Frenel Jean-Sébastien JS Guiu Séverine S Mouret-Reynier Marie-Ange MA Mailliez Audrey A Eymard Jean-Christophe JC Petit Thierry T Ung Mony M Desmoulins Isabelle I Augereau Paule P Bachelot Thomas T Uwer Lionel L Debled Marc M Ferrero Jean-Marc JM Clatot Florian F Goncalves Anthony A Chevrot Michael M Chabaud Sylvie S Cottu Paul P

Cancers 20230213 4

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 accord ...[more]

PMID: 36831532

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Project description:BackgroundResistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity.MethodsIn this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed.ResultsBaseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). At the interim analysis, median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confidence interval [CI], 0.35 to 0.54; P<0.001). Median progression-free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001).ConclusionsEverolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials.gov number, NCT00863655.).

Project description:BackgroundEverolimus is beneficial for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). However, some patients developed drug resistance and the well-established predictor for everolimus efficacy was limited.ObjectivesThe study was designed to evaluate the efficacy of everolimus in different treatment lines and identify several clinicopathological markers to estimate everolimus efficacy in patients with HR+/HER2- ABC.DesignThis was a retrospective and multicenter study.MethodsBetween 2014 and 2022, more than 2000 patients with tumors who received everolimus were collected from multiple cancer centers in China (National Cancer Center, Chinese PLA General Hospital, Peking University Cancer Hospital & Institute). A training cohort and two validation cohorts were developed.ResultsThe training cohort included 338 patients. The median progression-free survival (PFS) for everolimus was 5.6 months, with an objective response rate of 25.1% and a clinical benefit rate of 54.4%. PFS was significantly worse from first-line (1L) to second-line (2L) to third-line (3L), with PFS1L for 13.5 months, PFS2L for 6.1 months, and PFS3L for 4.1 months (p = 2.9e-6, hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.61-0.82). The clinicopathological characteristics, including post-1L everolimus treatment, Ki67 index of more than 40%, more than two metastatic sites at first recurrence, and receiving adjuvant chemotherapy, were independent risk factors for PFS. A predictive model for everolimus efficacy was established using these four factors. In the low-risk group, patients achieved a median PFS of 12.6 months, significantly longer compared to 2.7 months for those in the high-risk group (p = 2.4e-64, HR = 9.41, 95% CI = 7.05-12.56). The area under the curve was 0.96, 0.95, and 0.94 for 6-month, 1-year, and 3-year PFS, respectively. Internal validation cohort (PFS 18.4 vs 3.1 months, p = 3.6e-11, HR = 3.78, 95% CI = 2.49-5.74) and external validation cohort (PFS 13.5 vs 3.1 months, p = 2.9e-10, HR = 11.53, 95% CI = 4.68-28.37) confirmed its power for estimating clinical benefits of everolimus.ConclusionA predictive model was successfully established to predict survival outcomes for everolimus in patients with HR+/HER2- ABC, which may provide references for the management of everolimus in Chinese patients with HR+/HER2- ABC.

Project description:ObjectiveLimited real-world efficacy and safety data exist regarding the use of trastuzumab deruxtecan (T-DXd) in the Chinese population with human epidermal growth factor receptor (HER2)-positive and HER2-low advanced breast cancer (BC). This multicenter, observational, real-world study aimed to evaluate the efficacy and safety of T-DXd for the treatment of Chinese patients with HER2-positive and HER2-low advanced BC.MethodsThe medical records of 61 patients were collected from The Second Hospital of Dalian Medical University, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing Jingxin Hospital, and Cancer Hospital of the Chinese Academy of Medical Sciences. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to response (TTR), and safety. PFS and OS were analyzed using the Kaplan-Meier method and log-rank test.ResultsThe primary endpoint, PFS was 10.51 months (95% confidence interval (CI), 3.02-NE) in the HER2-low group and 10.18 months (95% CI, 3.88-NE) in the HER2-positive group. Regarding the secondary endpoints in the HER2-low and HER2-positive groups, OS data were immature, ORR rates were 37.93% and 62.50%, DCR rates were 79.31% and 87.50%, and the median TTR rates were 1.28 and 1.31 months, respectively. In the subgroup analysis, front-line treatment with T-DXd was associated with increased beneficial effects. The primary adverse events (AEs) related to T-DXd treatment were gastrointestinal reactions and bone marrow suppression, which were predominantly grades 1-2, with no severe grade 4/5 AEs reported, only one patient developed infectious pneumonia.ConclusionThis study was the first multicenter, real-world study of T-DXd for advanced BC in China. The findings demonstrated that T-DXd may be an effective antitumor treatment with controllable adverse reactions in patients with advanced BC irrespective of HER2 expression levels.

Project description:BackgroundNivolumab is the first immune checkpoint inhibitor approved in Europe for the treatment of advanced renal cell carcinoma (aRCC) in patients resistant to prior antiangiogenic therapy. WITNESS is an ongoing, prospective, observational study designed to evaluate the effectiveness and safety of nivolumab in patients with aRCC treated in real life (or routine practice) in France (ClinicalTrials.gov identifier: NCT03455452).Patients and methodsThis study includes adult patients with a confirmed diagnosis of aRCC who have initiated nivolumab after 1-2 prior lines of antiangiogenic therapy. Endpoints include overall survival (OS), progression-free survival (PFS), duration of treatment (DOT), duration of response (DOR), overall response rate (ORR), subgroup analyses, and treatment-related adverse events (TRAEs). Results after a median follow-up of 12.3 months are presented here.ResultsA total of 325 patients with aRCC were included, of whom 38.2% had a Karnofsky score <80, 77.8% received nivolumab as second-line therapy, and 69.5% had undergone a previous nephrectomy. In the overall population, median OS was 20.5 [95% confidence interval (CI) 17.6-25.0] months and median PFS was 5.2 (95% CI 4.5-5.9) months. ORR was 34.5%, median DOT was 3.8 months, and median DOR was 16.5 months. Nivolumab was effective in different subgroups including patients with bone or glandular metastases and those receiving baseline corticosteroids. Moreover, effectiveness was observed irrespective of prior nephrectomy and line of treatment. No new safety signals were identified; TRAEs of any grade were reported in 32.0% of patients, grade ≥3 and serious TRAEs in 11.1% each, and TRAEs leading to discontinuation in 8.9%.ConclusionsPreliminary results of the ongoing WITNESS study confirm the real-world effectiveness and safety of nivolumab monotherapy in previously treated patients with aRCC. Treatment benefits were similar to those observed in the pivotal phase III CheckMate 025 randomized clinical trial, despite a broader, real-life study population.

Project description:BACKGROUND:The prognostic and predictive value of the two nonluminal (human epidermal growth factor receptor 2 [HER2]-enriched and basal-like) subtypes within advanced hormone receptor-positive (HR+) breast cancer is currently unknown. MATERIALS AND METHODS:This study retrospectively analyzed 261 tumors (80.7% primary; 19.3% metastatic) from the BOLERO-2 study; BOLERO-2 randomized 724 patients with advanced HR+/HER2-negative breast cancer to everolimus plus exemestane or placebo plus exemestane. Tumors were classified using a PAM50 subtype predictor. Multivariable Cox regression analyses tested the independent prognostic significance of PAM50, and associations between PAM50 subtypes and treatment upon progression-free survival (PFS) were evaluated. RESULTS:Subtype distribution was 46.7% luminal A (n = 122), 21.5% HER2-enriched (n = 56), 15.7% luminal B (n = 41), 14.2% normal-like (n = 37), and 1.9% basal-like (n = 5); HER2-enriched subtypes were more common in metastatic versus primary tumors (32.0% vs. 18.7%; p = .038). Median PFS differences between luminal and nonluminal (6.7 vs. 5.2 months; adjusted hazard ratio, 0.66; 95% confidence interval [CI], 0.47-0.94; p = .020) and HER2-enriched and non-HER2-enriched subtypes (5.2 vs. 6.2 months; adjusted hazard ratio, 1.53; 95% CI, 1.07-2.19; p = .019) were significant. Everolimus plus exemestane significantly improved median PFS versus placebo plus exemestane among patients with HER2-enriched tumors (5.8 vs. 4.1 months; adjusted hazard ratio, 0.49; 95% CI, 0.26-0.90; p = .034); however, the association between HER2-enriched tumors and everolimus benefit was nonsignificant (p = .433). CONCLUSION:The HER2-enriched subtype was identified in a substantial proportion of advanced HR+/HER2-negative breast tumors, and was a consistent biomarker of poor prognosis. Tailored therapies are therefore needed for HER2-enriched tumors in the advanced HR+/HER2-negative breast cancer setting. IMPLICATIONS FOR PRACTICE:Using 261 tumor samples from the BOLERO-2 phase III clinical trial, this study shows that a substantial proportion (20%-30%) of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancers do not have a luminal A or B gene expression profile. This group of patients with nonluminal disease has a poor survival outcome regardless of the addition of everolimus to exemestane. This is the second study that confirms the prognostic value of this biomarker. Overall, these findings indicate a necessity to design novel clinical trials targeting nonluminal disease within HR+/HER2-negative breast cancer.

Dataset Information

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

Publications

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

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