Dataset Information

Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR⁺/HER2^- Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1).

ABSTRACT:

Purpose

Standard-of-care treatment for metastatic hormone receptor-positive (HR⁺), HER2-negative (HER2^-) breast cancer includes endocrine therapy (ET) combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Optimal treatment after progression on CDK4/6i is unknown. The TRINITI-1 trial investigated ribociclib, a CDK4/6i that has recently demonstrated significant overall survival benefit in two phase III trials, in combination with everolimus and exemestane in patients with HR⁺, HER2^- advanced breast cancer (ABC) after progression on a CDK4/6i.

Patients and methods

This multicenter, open-label, single-arm, phase I/II study included patients with locally advanced/metastatic HR⁺/HER2^- breast cancer. The primary endpoint was clinical benefit rate (CBR) at week 24 among patients with ET-refractory disease with progression on a CDK4/6i. Other endpoints included safety and biomarker analysis.

Results

Of 104 patients enrolled (phases I and II), 96 had prior CDK4/6i. Recommended phase II doses (all once daily days 1-28 of 28-day cycle) were ribociclib 300 mg, everolimus 2.5 mg, and exemestane 25 mg (group 1) and ribociclib 200 mg, everolimus 5 mg, and exemestane 25 mg (group 2). CBR among 95 efficacy-evaluable patients (phases I and II) at week 24 was 41.1% (95% confidence interval, 31.1-51.6), which met the primary endpoint (predetermined threshold: 10%). Common adverse events included neutropenia (69.2%) and stomatitis (40.4%). No new safety signals were observed; no grade 3/4 QTc prolongation was reported.

Conclusions

Preliminary TRINITI-1 safety and efficacy results support further investigation of CDK4/6 blockade and targeting of the PI3K/AKT/mTOR signaling pathway in patients with ET-refractory HR⁺/HER2^- ABC after progression on a CDK4/6i.

SUBMITTER: Bardia A

PROVIDER: S-EPMC8487593 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR<sup>+</sup>/HER2<sup>-</sup> Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1).

Bardia Aditya A Hurvitz Sara A SA DeMichele Angela A Clark Amy S AS Zelnak Amelia A Yardley Denise A DA Karuturi Meghan M Sanft Tara T Blau Sibel S Hart Lowell L Ma Cynthia C Rugo Hope S HS Purkayastha Das D Moulder Stacy S

Clinical cancer research : an official journal of the American Association for Cancer Research 20210315 15

<h4>Purpose</h4>Standard-of-care treatment for metastatic hormone receptor-positive (HR<sup>+</sup>), HER2-negative (HER2<sup>-</sup>) breast cancer includes endocrine therapy (ET) combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Optimal treatment after progression on CDK4/6i is unknown. The TRINITI-1 trial investigated ribociclib, a CDK4/6i that has recently demonstrated significant overall survival benefit in two phase III trials, in combination with everolimus and exemestane i ...[more]

PMID: 33722897

Similar Datasets

Project description:PurposeCDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy are considered standard-of-care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced breast cancer (HR+/HER2- ABC). Superiority of combination therapy over endocrine monotherapy has been demonstrated in a multitude of randomized controlled trials (RCTs) in phase III and IV. However, RCTs reflect clinical reality only to a limited extent, as narrow inclusion criteria lead to a selected patient collective. Here, we present real-world data (RWD) on CDK4/6i treatment in patients with HR+/HER2- ABC at four certified German university breast cancer centers.MethodsPatients diagnosed with HR+/HER2- ABC who were treated in clinical routine with CDK4/6i between November 2016 and December 2020 at four certified German university breast cancer centers (Saarland University Medical Center, University Medical Center Charité Berlin, University Medical Center Bonn, and University Medical Center Hospital Schleswig-Holstein, Campus Kiel) were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on CDK4/6i therapy course [progression-free survival (PFS) following treatment initiation, toxicity, dose reduction, therapy discontinuation, prior and subsequent therapy line].ResultsData from n = 448 patients were evaluated. The mean patient age was 63 (±12) years. Of these patients, n = 165 (36.8%) were primarily metastasized, and n = 283 (63.2%) had secondary metastatic disease. N = 319 patients (71.3%) received palbociclib, n = 114 patients (25.4%) received ribociclib, and n = 15 patients (3.3%) received abemaciclib, respectively. Dose reduction was performed in n = 132 cases (29.5%). N = 57 patients (12.7%) discontinued the treatment with CDK4/6i due to side effects. N = 196 patients (43.8%) experienced disease progression under CDK4/6i treatment. The median PFS was 17 months. Presence of hepatic metastases and prior therapy lines were associated with shorter PFS, whereas estrogen positivity and dose reduction due to toxicity were positively associated with PFS. Presence of bone and lung metastases, progesterone positivity, Ki67 index, grading, BRCA1/2 and PIK3CA mutation status, adjuvant endocrine resistance, and age did not significantly impact on PFS.ConclusionOur RWD analysis on CDK4/6i treatment in Germany supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2- ABC. In comparison to data from the pivotal RCTs, median PFS was lower but within the expected range for RWD, which could result from inclusion of patients with more advanced diseases (i.e., higher therapy lines) to our dataset.

Project description:BackgroundAdvanced breast cancer (ABC) is characterized by multidimensional clinical complexity that is usually not considered in randomized clinical trials. In the present real-life study, we investigated the link between clinical complexity and quality of life of patients with HR+/HER2- ABC treated with CDK4/6 inhibitors.MethodsWe evaluated multimorbidity burden assessed with the Cumulative Illness Rating Scale (CIRS), polypharmacy and patient-reported outcomes (PROs). PROs were assessed at baseline (T0), after 3 months of therapy (T1), and at disease progression (T2) using EORTC QLC-C30 and QLQ-BR23 questionnaires. Baseline PROs and changes between T0 and T1 were evaluated amongst patients with different multimorbidity burden (CIRS <5 and ≥5) and polypharmacy (<2 or ≥2 drugs).ResultsFrom January 2018 to January 2022, we enrolled 54 patients (median age 66 years, IQR 59-74). The median CIRS score was 5 (IQR 2-7), whilst the median number of drugs taken by patients was 2 (IQR 0-4). No changes in QLQ-C30 final scoring between T0 and T1 were observed in the overall cohort (p=0.8944). At T2, QLQ-C30 global score deteriorated with respect to baseline (p=0.0089). At baseline, patients with CIRS ≥5 had worse constipation than patients without comorbidities (p<0.05) and a lower trend in the median QLQ-C30 global score. Patients on ≥2 drugs had lower QLQ-C30 final scores and worse insomnia and constipation (p<0.05). No change in QLQ-C30 final score from T0 to T1 was observed (p>0.05).ConclusionMultimorbidity and polypharmacy increase the clinical complexity of patients with ABC and may affect baseline PROs. The safety profile of CDK4/6 inhibitors seems to be maintained in this population. Further studies are needed to assess clinical complexity in patients with ABC.This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special_issues/tackling-clinical-complexity-in-breast-cancer/.

Dataset Information

Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR⁺/HER2^- Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1).

Purpose

Patients and methods

Results

Conclusions

Publications

Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR<sup>+</sup>/HER2<sup>-</sup> Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR+/HER2- Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1).

Purpose

Patients and methods

Results

Conclusions

Publications

Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR<sup>+</sup>/HER2<sup>-</sup> Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR⁺/HER2^- Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1).