Intermediate endpoints as surrogates for long term outcomes in breast cancer adjuvant chemotherapy trials.

Background: Several definitions of efficacy endpoints have been proposed for clinical trials in early breast cancer (EBC). Invasive disease-free survival (IDFS) and other endpoints have been used as surrogates for overall survival (OS) in adjuvant trials. The aim was to evaluate these endpoints in a comparative way in a large cohort of patients to assess whether they are appropriate surrogates for OS.

Camizestrant in combination with three globally approved CDK4/6 inhibitors in women with ER+, HER2- advanced breast cancer: Results from SERENA-1.

Purpose: This trial investigated safety and tolerability of camizestrant with CDK4/6 inhibitors (CDK4/6i), in women with ER+, HER2- advanced breast cancer.

Patients And Methods: SERENA-1 (NCT03616587) is a Phase 1, multi-part, open-label study in women with refractory ER+, HER2- advanced breast cancer. Patients received oral once-daily camizestrant 75 or 150 mg plus abemaciclib; camizestrant 75, 150, or 300 mg plus palbociclib; or camizestrant 75 mg plus ribociclib 400 or 600 mg.

Hormonal factors predictive of fertility in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy in POSITIVE trial.

Purpose: The POSITIVE trial showed that premenopausal women with breast cancer (BC) can safely pause adjuvant endocrine treatment (ET) to attempt conception. 74 % of patients conceived spontaneously or through assisted reproductive technology (ART); Investigating hormonal factors that predict fertility was a key secondary endpoint.

Methods: Hormonal factors were assessed in non-pregnant women at months 3, 6, and 12 after ET interruption.

Transcriptomic Predictors of Survival for Palbociclib + Endocrine Therapy Versus Capecitabine in Aromatase Inhibitor-Resistant Breast Cancer From the GEICAM/2013-02 PEARL Trial.

Purpose: For hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC), first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) is the standard of care. They are also used after progression on first-line aromatase inhibitors (AIs), but some patients may respond better to chemotherapy-based options. We examined tumor features associated with survival from GEICAM/2013-02 PEARL, a phase III trial of palbociclib + ET versus capecitabine in AI-resistant HR+/HER2- MBC.

Prevention of sacituzumab govitecan-related neutropenia and diarrhea in patients with HER2-negative advanced breast cancer (PRIMED): an open-label, single-arm, phase 2 trial.

Background: Neutropenia and diarrhea are common sacituzumab govitecan-related adverse events, frequently leading to treatment modifications. PRIMED evaluated primary prophylactic granulocyte colony-stimulating factor (G-CSF) and loperamide to improve sacituzumab govitecan tolerability.

Methods: PRIMED (NCT05520723) was an open-label, single-arm, phase II study that enrolled HER2-negative advanced breast cancer patients previously treated with 1-2 chemotherapy regimens for metastatic disease.

FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial.

Purpose: In a prespecified GEICAM_CIBOMA trial (NCT00130533) correlative analysis, PAM50 non-basal-like breast cancer (non-BLBC) status distinguished patients with triple-negative breast cancer (TNBC) who are most likely to benefit from adjuvant capecitabine. The standardized forkhead box C1 (FOXC1) IHC test has demonstrated strong reliability in classifying the BLBC subtype throughout TNBC cohorts. This translational analysis aimed to evaluate the prognostic/predictive significance of BLBC classification by FOXC1 IHC in the phase III GEICAM_CIBOMA clinical trial.

Atezolizumab plus paclitaxel and bevacizumab as first-line treatment of advanced triple-negative breast cancer: the ATRACTIB phase 2 trial.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis. The current first-line treatment for advanced TNBC (aTNBC) is determined by the expression of programmed cell death-ligand 1 (PD-L1). In the ATRACTIB trial-a multicenter, single-arm, phase 2 study-we evaluated the combination of atezolizumab, paclitaxel and bevacizumab as first-line treatment for patients with aTNBC, independently of PD-L1 status.

Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial.

Leptomeningeal metastatic disease (LMD) is a severe complication of solid cancers with poor outcomes and limited treatment options. The antibody-drug conjugate patritumab deruxtecan (HER3-DXd) demonstrated efficacy in breast and lung cancers, and HER3 is involved in central nervous system metastases, particularly in parenchymal colonization. In this study, we investigated HER3-DXd efficacy and safety in patients with LMD in cohort 3 of the TUXEDO-3 phase 2 trial.

Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: primary results from a two-part, multicentre, single-arm, phase 2a study.

Background: New HER2-targeted regimens, including chemotherapy-free options, are needed for metastatic breast cancer. In an ongoing, two-part, phase 2a study, we assessed the safety and antitumour activity of zanidatamab, a HER2-targeted bispecific antibody, plus palbociclib and fulvestrant, in heavily pretreated patients with hormone receptor-positive, HER2-positive advanced or metastatic breast cancer.

Methods: This multicentre, single-arm, two-part, phase 2a study is being conducted at 13 university hospitals, cancer centres, or research institutes in Spain, Canada, and the USA.

Body mass index as a predictive factor for efficacy of adjuvant taxane-based chemotherapy in early-stage breast cancer patients: A pooled analysis from adjuvant GEICAM Spanish Breast Cancer Group and TRIO Translational Research in Oncology Group studies.

Adjuvant anthracyclines and taxanes reduce recurrence and death in early-stage breast cancer (EBC) patients, but toxicity is a concern. Studies show conflicting results on the correlation between body mass index (BMI) and outcomes. Limited data exist on the efficacy of adjuvant taxanes among BMI categories and the impact of different taxane-based chemotherapies (paclitaxel vs.

Retrospective analysis to validate the CTS5 in patients from El Álamo IV registry and GEICAM adjuvant studies.

Background: Identifying high-risk of late recurrence (beyond 10 years) in patients with hormone receptor-positive HER2-negative early breast cancer (EBC) is crucial. The Clinical Treatment Score post-5 years (CTS5) score assesses recurrence risk after 5 years of endocrine therapy (ET). This study validated CTS5 as a prognostic tool for late recurrence by examining its association with Distant Recurrence-Free Survival using GEICAM study data and evaluating model calibration.

TUXEDO-4: phase II study of trastuzumab-deruxtecan in HER2-low breast cancer with new or progressing brain metastases.

NCT06048718 (clinicaltrials.gov); 2023 -506,702-39-00 (EudraCT number).

Predictive factors for complete pathologic response in luminal breast cancer: impact of ki67 and HER2 low expression.

Background: Complete pathological response to neoadjuvant treatment (NAT) in breast cancer is associated with prolonged survival. Compared to other breast cancer immunophenotypes, luminal tumors are the least chemosensitive with low rates of pathological response within this molecular subtype. Thus, finding predictors of response in this subset remains challenging.

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study.

Background: Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A.

Methods: This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide.

SGLT2 inhibition improves PI3Kα inhibitor-induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials.

Purpose: Alpelisib plus fulvestrant demonstrated a significant progression-free survival benefit versus fulvestrant in patients with PIK3CA-mutated HR+ /HER2- advanced breast cancer (ABC) (SOLAR-1). Hyperglycemia, an on-target adverse effect of PI3Kα inhibition, can lead to dose modifications, potentially impacting alpelisib efficacy. We report data from preclinical models and two clinical trials (SOLAR-1 and BYLieve) on Sodium glucose cotransporter 2 inhibitor (SGLT2i) use to improve PI3Kα inhibitor-associated hyperglycemia.

Selecting postoperative adjuvant systemic therapy for early-stage breast cancer: An updated assessment and systematic review of leading commercially available gene expression assays.

Gene expression assays (GEAs) can guide treatment for early-stage breast cancer. Several large prospective randomized clinical trials, and numerous additional studies, now provide new information for selecting an appropriate GEA. This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®).

Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer.

Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study.

Retrospective registry of patients with locally advanced/metastatic HR/HER2 breast cancer treated in clinical practice in Andalusia.

Background: Limited data are available regarding the real-world effectiveness and safety of Cyclin Dependent Kinase 4/6 inhibitor (CDK4/6i) (palbociclib/ribociclib) just as a first-line treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2‒) metastatic breast cancer (MBC).

Objective: To assess whether clinical or demographic characteristics limit access to first-line CDK4/6i treatment in clinical practice in the Autonomous Community of Andalusia (Spain) between November 2017 and April 2020. In addition, effectiveness will be described in an exploratory analysis.

Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial.

Background: In DESTINY-Breast02, patients with HER2-positive unresectable or metastatic breast cancer who received trastuzumab deruxtecan demonstrated superior progression-free and overall survival compared with those receiving treatment of physician's choice. We present the patient-reported outcomes (PROs) and hospitalisation data.

Methods: In this randomised, open-label, phase 3 trial conducted at 227 clinical sites globally, enrolled patients had to be aged 18 years or older with HER2-positive unresectable or metastatic breast cancer that had progressed on trastuzumab emtansine and had an Eastern Cooperative Oncology Group performance status of 0 or 1.

Preventing alpelisib-related hyperglycaemia in HR+/HER2-/-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trial.

Background: Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2-/-mutated advanced breast cancer (ABC).

Methods: Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2-/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose <100 mg/dL [<5.