The phase IIIb CompLEEment-1 study evaluated ribociclib plus letrozole in patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast ...cancer (ABC). Outcomes were investigated in the following subgroups: central nervous system (CNS) metastases, prior chemotherapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, and visceral metastases plus prior chemotherapy for advanced disease or ECOG PS 2.
Patients with HR+, HER2– ABC without prior hormonal treatment for advanced disease received oral ribociclib (600 mg once daily, 3 weeks on/1 week off) plus letrozole (2.5 mg once daily, continuous). Primary endpoint was safety/tolerability, assessed via occurrence of adverse events (AEs); key secondary endpoints included time to progression (TTP), overall response rate, and clinical benefit rate.
51 patients had CNS metastases, 194 received prior chemotherapy for advanced disease, 112 had ECOG PS 2, 146 had visceral metastases plus prior chemotherapy, and 77 had visceral metastases plus ECOG PS 2. Safety results were consistent with those in the overall CompLEEment-1 population; no new safety concerns were identified. The AE profile was manageable with low rates of discontinuations due to AEs. TTP in patients with CNS metastases was consistent with the overall study population and shorter for other patient subgroups. Each patient subgroup achieved meaningful clinical benefit from treatment, consistent with the overall population.
These findings confirm the clinical benefit of ribociclib plus endocrine therapy in high-risk patient subgroups of clinical interest commonly underrepresented in clinical trials.
•CompLEEment-1 evaluated ribociclib plus letrozole in patients with HR+, HER2– ABC.•Outcomes were evaluated in 5 patient subgroups with traditionally poor prognosis.•The AE profile was manageable; there were low rates of discontinuations due to AEs.•Patients in each subgroup achieved meaningful clinical benefit from treatment.
Breast cancer is one of the most prevalent tumors among women. Its prognosis and treatment outcomes depend on factors related to tumor cell biology. However, recent studies have revealed the critical ...role of the tumor microenvironment (TME) in the development, progression, and treatment response of breast cancer. In this review, we explore the different components of the TME and their relevance as prognostic and predictive biomarkers in breast cancer. In addition, techniques for assessing the tumor microenvironment, such as immunohistochemistry or gene expression profiling, and their clinical utility in therapeutic decision-making are examined. Finally, therapeutic strategies targeting the TME are reviewed, highlighting their potential clinical benefits. Overall, this review emphasizes the importance of the TME in breast cancer and its potential as a clinical tool for better patient stratification and the design of personalized therapies.
By the end of 2020, there were more than 8 million women alive who had received a breast cancer diagnosis in the previous 5 years, making it the most prevalent neoplasia in the world. About 70% of ...breast-cancer cases present positivity for estrogen and/or progesterone receptors and a lack of HER-2 overexpression. Endocrine therapy has traditionally been the standard of care for ER-positive and HER-2-negative metastatic breast cancer. In the last 8 years, the advent of CDK4/6 inhibitors has shown that adding them to endocrine therapy doubles PFS. As a result, this combination has become the gold standard in this setting. Three CDK4/6 inhibitors have been approved by the EMA and the FDA: abemaciclib, palbociclib, and ribociclib. They all have the same indications, and it is at each physician's discretion to choose one or the other. The aim of our study was to perform a comparative efficacy analysis of the three CDK4/6i using real-world data. We selected patients diagnosed with endocrine-receptor-positive and HER2-negative breast cancer who were treated with all three CDK4/6i as first-line therapy at a reference center. After 42 months of retrospective follow up, abemaciclib was associated with a significant benefit in terms of progression-free survival in endocrine-resistant patients and in the population without visceral involvement. In our real-world cohort, we found no other statistically significant differences among the three CDK4/6 inhibitors.
Resumen Introducción: la desnutrición en los pacientes oncológicos puede conllevar una reducción de la calidad de vida del paciente y un aumento de la morbimortalidad y de los costes sanitarios ...asociados. Objetivos: analizar las intervenciones nutricionales en las diferentes fases del proceso oncológico, integrando las necesidades de los pacientes y las de los profesionales sanitarios. Material y métodos: se utilizaron técnicas de Design Thinking para abordar el análisis de la situación actual e identificar los aspectos clave. Participaron 13 profesionales de 8 centros sanitarios (endocrinología y nutrición, oncología médica y radioterápica, atención primaria (AP), enfermería y dietética) públicos de Andalucía. Resultados: no se realiza cribado nutricional de forma sistemática en las diferentes fases del proceso oncológico, y no existe consenso universal en los protocolos de actuación e intervención nutricional. Existe un cumplimiento generalizado de los circuitos y tiempos de derivación de los procesos seleccionados. En la fase terapéutica se dispone de la posibilidad de consultar a la Unidad de Nutrición Clínica y Dietética (UNCYD) y el 75 % disponen de protocolos específicos de derivación. La enfermera gestora de casos está presente en todos los hospitales y en AP. El acceso del paciente al psicólogo del centro era posible en el 87 % de los hospitales. Escasa participación de la UNCYD en los Comités de Tumores (solo en el 25 % de los centros). En todos los centros existe algún tipo de colaboración y apoyo de las asociaciones de pacientes y de la Escuela de Pacientes, especialmente en las fases terapéuticas y de control y seguimiento. Conclusiones: se observan variaciones entre los diferentes hospitales y territorios de Andalucía, tanto en la disposición de medios y estructuras como en las actividades y procedimientos. Se han seleccionado y priorizado puntos clave para mejorar la atención nutricional en oncología.
The NOA (Oncological Nutrition in Andalusia) project analyses the degree of integration and areas of improvement in implementing nutritional support in the care plans of cancer patients in Andalusia. ...The aim was to analyse nutritional interventions for better care of cancer patients and for the improvement of the management of malnutrition in cancer. A prospective evaluation of the implementation of two areas of improvement in nutrition was conducted in three hospitals. Data were collected from each hospital over a six-month period using an online platform. A standardised care plan was designed for hospitals in Andalusia, in which proposed improvements were devised and prioritised, selecting nutritional screening in oncology services and the participation of the Nutrition Support Team (NST) on the tumour boards, as well as the assessment of the patients presented at these sessions. Our results indicated an increase in the number of medical records with nutritional evaluation results six months later, regardless of the type of tumour or hospitalisation; and there was greater participation of the NST on the tumour boards, mainly for head and neck and oesophagogastric cases. Solutions for improvement have been pinpointed and implemented that have positively impacted the nutritional care plan in the course of oncological disease.
Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in ...prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) vs. ET alone.
CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2– ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.
A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study.
Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2− ABC, including populations of interest (NCT02941926).
ClinicalTrials.gov NCT02941926
•Results from the CompLEEment-1 Spanish population are comparable to the global results.•Manageable safety was shown in elderly patients and those with visceral disease.•Efficacy data were comparable to those of the global study in a younger population.•Efficacy and safety of ribociclib are confirmed in a broader patient population.•Results confirm a robust response to treatment in a local setting.
Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at ...diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established.
Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival.
After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio HR, 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%).
For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.
Background: Reduced muscle strength (dynapenia) and mass (atrophy) are prognostic factors in oncology. Measuring maximal handgrip strength with dynamometers is feasible but limited by the cost of the ...reference device (JAMAR). Methods: A cross-sectional study was conducted on colorectal cancer outpatients treated with chemotherapy or under active surveillance in our center from September 2022 to July 2023. Accuracy, reliability, and concordance were compared for two handheld dynamometers: the JAMAR Plus (the gold-standard device) and the Camry EH101 (a low-cost index device). A simultaneous nutritional diagnosis with GLIM criteria and bioelectrical impedance analysis (BIA) was carried out. Results: A total of 134 participants were included. The median of maximal strength for the JAMAR Plus had a non-significant difference of 1.4 kg from the Camry EH101. The accuracy and reliability of the devices were high. Bland–Altman analysis showed a 0.8 kg bias and −4.1 to 5.6 kg limits of agreement (LoA); a 0.1 kg bias and −5.3 to 5.4 kg LoA in men; a 1.5 kg bias and −2.2 to 5.3 kg LoA in women. In total, 29.85% of the participants were malnourished. Prevalence of dynapenia increased from 3.67% with the JAMAR Plus to 5.14% with the Camry EH101. Both devices had a moderate and significant correlation with BIA-estimated muscle mass. Conclusions: The Camry EH101 was a cost-effective alternative to JAMAR Plus in our sample.
Preclinical data support a key role for the human epidermal growth factor receptor 3 (HER3) pathway in hormone receptor (HR)-positive breast cancer. Recently, new HER3 directed antibody drug ...conjugates have shown activity in breast cancer. Given the need to better understand the molecular biology, tumor microenvironment, and mechanisms of drug resistance in breast cancer, we designed this window-of-opportunity study with the HER3 directed antibody drug conjugate patritumab deruxtecan (HER3-DXd; U3-1402).
Based on these data, a prospective, multicenter, single-arm, window-of-opportunity study was designed to evaluate the biological effect of patritumab deruxtecan in the treatment of naïve patients with HR-positive/HER2-negative early breast cancer whose primary tumors are ≥1 cm by ultrasound evaluation. Patients will be enrolled in four cohorts according to the mRNA-based ERBB3 expression by central assessment. The primary endpoint is a CelTIL score after one single dose. A translational research plan is also included to provide biological information and to evaluate secondary and exploratory objectives of the study.
EudraCT 2019-004964-23; NCT number: NCT04610528.
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