Effectiveness and safety of neoadjuvant therapy in triple-negative breast cancer in a real-world population.

OBJECTIVE: Triple-negative breast cancer is a subtype of aggressive breast cancer. Our aim is to evaluate the effectiveness and safety of neoadjuvant treatment in early-stage triple-negative breast cancer and to identify predictors of pathological complete response. METHODS: This is a single-center, retrospective study involving 79 patients with triple-negative breast cancer who initiated neoadjuvant treatment between January 2017 and October 2022. Descriptive analyses were performed as appropriate. Statistical analysis utilized bivariate logistic regression to explore the presence of factors related to pathological complete response, and the Kaplan-Meier method was employed for survival analysis. RESULTS: In the overall population, 27 patients (n=78; 34.6%) achieved pathological complete response in the breast and axillary lymph nodes, and 31 (n=73; 42.5%) achieved a grade 5 pathological complete response in the breast, according to the Miller and Payne classification. The addition of platinum to standard therapy improved both breast and axillary lymph node pathological complete response rates. Age less than 40 years was identified as a predictor of pathological complete response in our study population through bivariate analysis, while Ki67 levels lower than 70% were associated with a lower pathological complete response rate. Adverse events were reported in 72 patients (91.1%), with grade 3-5 adverse events observed in 33 (41.8%). There was a particularly notable increase in gastrointestinal and hematological adverse events when platinum was added. CONCLUSIONS: In this population, we observed moderate rates of pathological complete response with acceptable chemotherapy tolerance. Platinum-based chemotherapy appears to enhance the likelihood of achieving pathological complete response, albeit with a less favorable safety profile. Therefore, evaluating the benefit-risk balance is crucial when selecting the optimal chemotherapy regimen for individual patients.

Real-world data of atezolizumab in patients with previously treated locally advanced or metastatic urothelial bladder cancer.

BACKGROUND: Clinical trials of atezolizumab for locally advanced or metastatic urothelial bladder cancer (mUBC) report controversial efficacy data. Furthermore, real-world evidence about this use is limited. AIM: We aimed to evaluate the effectiveness of atezolizumab in a real-world population with mUBC, to explore effectiveness with regard to selected poor prognostic criteria such as performance status by Eastern Oncology Cooperative Group (ECOG), hemoglobin levels and liver metastases, and to determine the safety profile of atezolizumab. METHOD: Multicenter, retrospective real-world study including previously treated mUBC patients who received atezolizumab. The primary endpoint was overall survival (OS). Additionally, progression-free survival (PFS), best response reached and safety data were analyzed. A descriptive analysis was performed, while OS and PFS were estimated by Kaplan-Meier method. RESULTS: A total of 185 patients (84.9% men, median age 69 years) were included. Median PFS was 4.8 months [95% confidence interval (CI) 3.6-6.0], and median OS was 20.0 months (95% CI 11.8-28.5), with an objective response rate of 28.1%. OS was higher for patients with ECOG 0-1 versus 2-3 [24.5 months (95% CI 14.5-34.6) vs. 5.2 (95% CI 4.4-6.0), p = 0.004]; and for patients without liver metastases [25.4 months (95% CI 16.2-34.6) vs. 6.4 months (95% CI 4.0-8.1), p = 0.006]. Regarding hemoglobin levels, no survival differences were detected. Adverse events were registered in 55.1% of patients. CONCLUSION: In a real-world population with previously treated mUBC, atezolizumab seems to provide clinically relevant benefit, which is even higher for patients with ECOG 0-1 and without liver metastases, with an acceptable safety profile.

Hypogammaglobulinemia after front-line immunochemotherapy in patients with follicular lymphoma.

INTRODUCTION: Hypogammaglobulinemia after front-line immunochemotherapy for follicular lymphoma is a poorly studied adverse event that could be related to the appearance of severe and/or recurrent non-neutropenic infections which could affect the quality of life of the patients, even motivating a need of long-term replacement therapy with human immunoglobulins. METHODS: Observational, retrospective study aiming to estimate the incidence of hypogammaglobulinemia, as well as its severity and clinical consequences, and to explore possible predictive factors for its development. Specific immunoglobulin deficiencies were also studied. RESULTS: 76.5% of patients had hypogammaglobulinemia during or after front-line treatment, mostly grade 1-2; with 38.8% patients who developed clinically relevant infections and 20% patients requiring human immunoglobulins replacement therapy. A high-risk FLIPI score was identified as a risk factor for hypogammaglobulinemia (ods ratio: 4.51; 95% confidence interval: 1.29-15.68; p < 0.001) and basal gamma globulin level as a protective factor (odds ratio: 0.92; 95% confidence interval: 0.988-0.996; p = 0.018). Any type of immunochemotherapy regimen was associated with different risks of hypogammaglobulinemia in our study. CONCLUSIONS: Hypogammaglobulinemia appears in a high percentage of patients with follicular lymphoma in a real-world population, identifying a high-risk FLIPI score as a risk factor for its development and basal gamma globulins as a protective factor.

Effectiveness and safety of eribulin for human epidermal growth factor receptor 2 negative metastatic breast cancer in a real-world population.

BACKGROUND: Eribulin's clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. PATIENTS AND METHODS: This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. RESULTS: A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1-11.4) and 2.8 months (95% confidence interval: 2.5-3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3-4.5) versus triple negative: 2.0 (95%confidence interval: 1.7-2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6-12.5 vs. 4.8 months, 95% confidence interval: 3.4-6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1-16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8-5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. CONCLUSION: Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.

Real world study of pertuzumab-trastuzumabchemotherapy versus trastuzumab-chemotherapy in neoadjuvant treatment of breast cancer.

OBJECTIVE: The primary objective of the study is to compare the  effectiveness of trastuzumab-chemotherapy with and without  pertuzumab. As a secondary objective, we seek to evaluate the cardiac  safety of the treatment. METHOD: Retrospective observational study including all patients treated with either pertuzumab-trastuzumab-chemotherapy (n = 10) or  trastuzumab-chemotherapy (n = 13) (January 2015-December 2018) in a specialty hospital, which met the criteria established by the  Commission Central for the Optimization and Harmonization of the  pharmacotherapy of the Andalusian Health Service for the use of  pertuzumab in neoadjuvance: HER2 positive tumor, negative hormonal  receptors, with high risk of relapse (tumor > 2 cm or lymph node  involvement). To assess effectiveness, the complete pathological  response was used. For cardiac safety, the decrease in left ventricular  ejection fraction greater than 10% was employed. RESULTS: Complete pathological response was superior in the  pertuzumab group (70.0% vs. 30.8%). Cardiac safety was similar in  both. CONCLUSIONS: For patients with HER2 positive tumors and negative hormonal receptors with high risk criteria that receive  pertuzumab, the complete pathological response is superior, with no  increase in cardiac toxicity.

Objetivo: El objetivo primario del estudio es comparar la efectividad trastuzumab-quimioterapia con y sin pertuzumab. Como  objetivo secundario se busca evaluar la seguridad cardiaca del  tratamiento.Método: Estudio observacional retrospectivo que incluyó todas las  pacientes tratadas con pertuzumab-trastuzumab-quimioterapia (n = 10) o trastuzumab-quimioterapia (n = 13) (enero 2015-diciembre 2018) en  un hospital de especialidades, que cumplían los criterios establecidos  por la Comisión Central para la Optimización y Armonización de la  farmacoterapia del Servicio Andaluz de Salud para uso de pertuzumab  en neoadyuvancia: tumor HER2 positivo, receptores hormonales  negativos, con alto riesgo de recaída (tumor > 2 cm o afectación  ganglionar). Para valorar la efectividad se utilizó la respuesta completa  patológica, y para la seguridad cardiaca, el descenso de la fracción de  eyección del ventrículo izquierdo superior al 10%.Resultados: La respuesta completa patológica fue superior en el grupo con pertuzumab (70,0% versus 30,8%). La seguridad cardiaca  fue similar en ambos.Conclusiones: Para las pacientes con tumores HER2 positivo y  receptores hormonales negativos con criterios de alto riesgo que reciben  pertuzumab, la respuesta completa patológica resulta superior,  sin observarse incremento de la toxicidad cardiaca.

A multicentre observational study of the effectiveness, safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice.

Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective The aim of this study was to evaluate the effectiveness, safety and economic cost of nivolumab in real-world clinical practice. Setting Fifteen regional and academic hospitals from Spain participated in this study. Methods This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system. Main outcome measures Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable. Results A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8-8.1). The median PFS was 5.3 months (95% CI 3.2-7.3), and OS was 9.7 months (95% CI 7.6-11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0-1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00-€231,171.00). Conclusions This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0-1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.