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 |

REPOSITORIES: biostudies-literature

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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

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

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).