Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2- advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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). TRIAL REGISTRATION: ClinicalTrials.gov NCT02941926.

Brain metastases in colorectal cancer: prognostic factors and survival analysis.

PURPOSE: Colorectal cancer (CRC) brain metastases (BM) are an uncommon and late event. We aim to investigate the impact of clinical factors, treatment modalities and RAS/BRAF status on the outcomes of CRC patients with BM. PATIENTS: We retrospectively analysed CRC patients who developed BM in our centre between January 1997 and June 2017. Clinical factors, treatment modalities, RAS/BRAF status and survival were evaluated. RESULTS: Twenty-eight patients were recorded; 82% had left-sided (LS) CRC and 71% had lung metastases. Median time to BM diagnosis was 36 months (m) and 93% of patients received local treatment of BM (43% whole brain radiotherapy, 50% surgery). Right-sided (RS) CRC showed shorter time to BM, not previously described (9.3 vs 46.6 m for RS and LS CRC, respectively; HR = 4.7, p = 0.006). Median overall survival (mOS) from BM treatment was 9.5 m, better in patients who underwent surgery than those treated with radiotherapy alone (12.1 vs 4.6 m, respectively; HR = 0.3, p = 0.019) and in those without progressive metastatic extracranial disease (7.2 vs 20.9 m, for progressive and non-progressive, respectively; HR = 0.3, p = 0.056). Patients with two or more metastatic extracranial locations showed worse prognosis (5.9 vs 16.3 m, for > 2 vs 0-1, respectively; HR = 3.7, p = 0.015). RAS/BRAF status did not showed prognostic value. CONCLUSIONS: Time to BM diagnosis is shorter in RS CRC. The presence of two or more metastatic extracranial locations and progressive metastatic extracranial disease at the time of BM diagnosis could be bad prognosis factors for CRC BM patients.

Epidemiology and characteristics of febrile neutropenia in oncology patients from Spanish tertiary care hospitals: PINNACLE study.

Febrile neutropenia (FN) is one of the most common adverse events associated with myelosuppressive chemotherapy for cancer treatment. The objective of this study was to describe the incidence of hospitalization due to FN in Spanish tertiary care hospitals (PINNACLE study). This epidemiological, retrospective, multicenter, nationwide study involved 119 patients from oncology units of 10 Spanish tertiary care hospitals who were admitted for FN. The primary endpoint was to assess the epidemiology and characteristics of FN. The incidence of admissions due to FN in oncology patients was 2.0% (interquartile range [IQR], 1.6-3.0). In terms of fever and absolute neutrophil count (ANC), 37.0% of the patients had a temperature of ≥38.2°C and an ANC of ≤500/m3. The number of patients who received prophylactic treatment with granulocyte colony-stimulating factor (G-CSF) was significantly higher in the palliative group (32.6%) compared with that in the non-palliative group (13.5%). The hospital length of stay was significantly shorter in patients who received prophylactic G-CSF compared with those who did not (5.0 days; IQR, 4.0-9.0 vs. 7.0 days; IQR, 5.0-11.0, respectively). The hospital length of stay was also significantly shorter in patients receiving palliative treatment (5.0 days; IQR, 3.0-7.0) compared with those receiving non-palliative therapy (7.0 days; IQR, 5.0-12.0). In conclusion, the incidence of admissions due to FN in oncology patients was 2.0% and the duration of hospital stay was 7.0 days. Prophylactic G-CSF treatment was found to be associated with better outcomes and shorter hospital stays. Therefore, the use of this treatment becomes relevant for achieving better clinical outcomes and reducing hospitalization cost in the management of FN.

[Sequential designs and intermediate analysis in clinical research: size vs difficulty]. / Diseños secuenciales y análisis intermedio en la investigación clínica: tamaño frente a dificultad.

Sequential design differs from other statistical designs used in clinical research in that the sample size is not fixed in advance but it varies depending on the results obtained. The intermediate analysis is defined as the treatment evaluation during an initial stage of the study and may lead to the termination of the study. Treatment effect with respect to control is evaluated across a series of pre-established time intervals. The study should be halted if there are significant differences in the level of overall significance, alpha. If this does not happen, then the study continues until reaching a maximum sample size, n, at which point the study ends and the hypothesis of equality is accepted. In general, sequential designs require fewer patients, although they make the study more complex because there is a need for continuous information about the patients' status; this latter aspect requires greater effort in terms of both study monitoring and patient follow-up. The aim therefore is to find a balance between smaller sample size (n) and greater complexity.

Diseños secuenciales y análisis intermedio en la investigación clínica: tamaño frente a dificultad / Sequential designs and intermediate analysis in clinical research: size vs difficulty

A diferencia de otros diseños estadısticos utilizados en la investigación clínica, en el diseño secuencial no se fija el tamaño muestral previamente, sino que éste varía en función de los resultados que se van obteniendo. El análisis intermedio se define como la evaluación del tratamiento durante una etapa inicial del estudio y puede conducir a la finalización del estudio. El efecto del tratamiento respecto al control se evaluará durante una serie de intervalos de tiempo prefijados. Se deberá detener el estudio si hay diferencias estadísticamente significativas en el nivel designificación global a; en caso contrario se continuará con el estudio hasta llegar a un tamaño (...) (AU)

Sequential design differs from other statistical designs used in clinical research in that the sample size is not fixed in advance but it varies depending on the results obtained. The intermediate analysis is defined as the treatment evaluation during an initial stage of the study and may lead to the termination of the study. Treatment effect with respect to control is evaluated across a series of pre-established time intervals. The study should be halted if there are significant differences in the level of overall significance, α. If this does not happen, then the study continues until reaching a maximum sample size, n, at which point the study ends and the hypothesis of equality is accepted. In general, sequential designs require fewer patients, although they make the study more complex because there is a need for continuous information about the patients’ status; this latter aspect requires greater effort in terms of both study monitoring and patient follow-up. The aim therefore is to find a balance between smaller sample size (n) and greater complexity (AU)