Real-world experience with pertuzumab and trastuzumab combined with chemotherapy in neoadjuvant treatment for patients with early-stage HER2-positive breast cancer: the NEOPERSUR study.

PURPOSE: HER2-targeted therapies have dramatically improved outcomes of patients with HER2-positive breast cancer (BC), as demonstrated in neoadjuvant trials. This study aims to provide real-world evidence on the use and effectiveness of combined pertuzumab, trastuzumab and chemotherapy (CT) in early-stage HER2-positive BC. METHODS: A retrospective, multicentre study was conducted on patients diagnosed with HER2-positive early BC treated with neoadjuvant pertuzumab and trastuzumab plus CT at 13 Spanish sites. The primary endpoint was pathological complete response (pCR). RESULTS: A total of 310 patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes, carboplatin and docetaxel, and taxane-based CT in 77.1%, 16.5%, and 6.5% of patients, respectively. Overall, the pCR rate was 62.2%. The pCR was higher amongst patients with hormone receptor-negative tumours and with tumours expressing higher levels of Ki-67 (> 20%). After postoperative adjuvant treatment, 13.9% of patients relapsed. Those patients who did not achieve pCR, with tumours at advanced stages (III), and with node-positive disease were more likely to experience distant relapse. Median overall survival (OS) and distant disease-free survival (D-DFS) were not reached at the study end. The estimated mean OS and D-DFS times were 7.5 (95% CI 7.3-7.7) and 7.3 (95% CI 7.1-7.5) years, respectively (both were significantly longer amongst patients who achieved pCR). Grade 3-4 anti-HER2 related toxicities were reported in six (1.9%) patients. CONCLUSION: Neoadjuvant pertuzumab and trastuzumab plus CT achieve high pCR rates in real-life patients with HER2-positive early BC, showing an acceptable safety profile. Innovative adjuvant strategies are essential in patients at high risk of distant disease recurrence.

Estudio en vida real de pertuzumab-trastuzumabquimioterapia frente a trastuzumab-quimioterapia en neoadyuvancia en cáncer de mama / Real world study of pertuzumab-trastuzumab-chemotherapy versus trastuzumab-chemotherapy in neoadjuvant treatment of breast cance

OBJETIVO: El objetivo primario del estudio es comparar la efectividad de trastuzumab-quimioterapia con y sin pertuzumab. Como objetivo secunda-rio se busca evaluar la seguridad cardiaca del tratamiento. MÉTODO: Estudio observacional retrospectivo que incluyó todas las pa-cientes 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 farma-coterapia 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 ven-trículo 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 recep-tores hormonales negativos con criterios de alto riesgo que reciben pertu-zumab, la respuesta completa patológica resulta superior, sin observarse incremento de la toxicidad cardiaca

OBJECTIVE: The primary objective of the study is to compare the effec-tiveness 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 trastuzu-mab-chemotherapy (n = 13) (January 2015-December 2018) in a special-ty 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 de-crease in left ventricular ejection fraction greater than 10% was employed. RESULTS: Complete pathological response was superior in the pertuzu-mab 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

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.

Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01).

PURPOSE: Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. PATIENTS AND METHODS: Eligible patients were those with operable, node-positive-or node negative with tumor 1 cm or greater-TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. RESULTS: Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P = .136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P = .0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P = .0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. CONCLUSION: This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation.