Triple-Negative PAM50 Non-Basal Breast Cancer Subtype Predicts Benefit from Extended Adjuvant Capecitabine.

PURPOSE: Predictive biomarkers for capecitabine benefit in triple-negative breast cancer (TNBC) have been recently proposed using samples from phase III clinical trials, including non-basal phenotype and biomarkers related to angiogenesis, stroma, and capecitabine activation genes. We aimed to validate these findings on the larger phase III GEICAM/CIBOMA clinical trial. EXPERIMENTAL DESIGN: Tumor tissues from patients with TNBC randomized to standard (neo)adjuvant chemotherapy followed by capecitabine versus observation were analyzed using a 164-gene NanoString custom nCounter codeset measuring mRNA expression. A prespecified statistical plan sought to verify the predictive capacity of PAM50 non-basal molecular subtype and tested the hypotheses that breast tumors with increased expression of (meta)genes for cytotoxic cells, mast cells, endothelial cells, PDL2, and 38 individual genes benefit from adjuvant capecitabine for distant recurrence-free survival (DRFS; primary endpoint) and overall survival. RESULTS: Of the 876 women enrolled in the GEICAM/CIBOMA trial, 658 (75%) were evaluable for analysis (337 with capecitabine and 321 without). Of these cases, 553 (84%) were profiled as PAM50 basal-like whereas 105 (16%) were PAM50 non-basal. Non-basal subtype was the most significant predictor for capecitabine benefit [HRcapecitabine, 0.19; 95% confidence interval (CI), 0.07-0.54; P < 0.001] when compared with PAM50 basal-like (HRcapecitabine, 0.9; 95% CI, 0.63-1.28; P = 0.55; Pinteraction<0.001, adjusted P value = 0.01). Analysis of biological processes related to PAM50 non-basal subtype revealed its enrichment for mast cells, extracellular matrix, angiogenesis, and features of mesenchymal stem-like TNBC subtype. CONCLUSIONS: In this prespecified correlative analysis of the GEICAM/CIBOMA trial, PAM50 non-basal status identified patients with early-stage TNBC most likely to benefit from capecitabine.

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.

Final results of an international retrospective observational study in patients with advanced breast cancer treated with oral vinorelbine-based chemotherapy.

BACKGROUND: Full oral chemotherapy (CT) is an active and convenient therapeutic option for patients with advanced breast cancer (ABC). In this retrospective analysis, we reviewed the characteristics and the outcome of patients treated by oral vinorelbine either as a single-agent or in combination with capecitabine as first- or second-line CT in the metastatic setting. PATIENTS AND METHODS: We analysed 216 patients with ABC who started treatment with a full oral CT at 13 centers and seven countries between 2006 and 2008. To be eligible, patients must have received either as a first-(56%) or second-line (44%) therapy oral vinorelbine as a single-agent (54%) or in combination with capecitabine (46%). RESULTS: Main patients' characteristics in the full population (n=216): median age (range): 61 (32-87) years; categories of age: <50 years: 18%, 50-65 years: 44%, ≥ 65 years: 38%; hormone receptor-positive: 63%; ≥ 2 metastatic sites: 58%; visceral metastases: 49%; prior CT: 86%; prior CT for ABC: 44%; prior anthracycline treatment: 69%; prior taxane treatment: 43%, prior anthracycline plus taxane: 38%; prior endocrine therapy: 63%. Median number of cycles: 6 (range=1-54); 48% of patients received more than 6 cycles. G3/4 toxicities: neutropenia 8%, anaemia 2%, thrombocytopenia 1%, febrile neutropenia/neutropenic infection 2%, nausea 6%, vomiting 4%, diarrhea 6%, fatigue 6%, hand-foot syndrome 14% (combination with capecitabine), neuropathy 1%, alopecia (grade 2) 1%. EFFICACY: disease control was achieved in 77% of patients [95% confidence interval=71-83%], 74% as single-agent, 81% in combination, 82% in first-line, 71% in second-line. Median progression-free survival was 9.7 months [95% confidence interval=8.2-12.6 months] in first-line and 6.6 months [95% confidence interval=5.5-8.5 months] in second-line therapy. Caregivers described these oral regimens as convenient (81%), well-tolerated (84%) and with a good compliance by patients (76%). CONCLUSION: These data from everyday practice confirm, as shown in different clinical trials, that oral vinorelbine is an active and well-tolerated CT for ABC, either as a first- or second-line in patients pre-treated with anthracyclines or taxanes. The convenience of its oral administration in association with its good tolerance profile, allows for continuation of treatment until disease progression without a pre-planned maximum of cycles.

Estudio fase II de docetaxel en pacientes con cáncer de mama avanzado sin tratamiento previo con quimioterapia citotóxica / Phase II study of docetaxel in patients with advance breat cancer without previous treatment and cytotoxic chemotherapy

Objetivo: Investigar la respuesta y seguridad de docetaxel como terapia de primera línea en cáncer metastásico de mama. Material y métodos: De marzo a octubre de 1994 se incluyeron 16 pacientes con cáncer mamario metastásico; el promedio de edad fue de 46 años y el estado funcional de 0-1; seis con quimioterapia adyuvante; las metástasis más frecuentes fueron a partes blandas, pulmón y huesos. El tratamiento consistió en docetaxel 100 mg x m² de superficie corporal cada tes semanas con premedicación a base de cetirizina más prednisona. Catorce casos fueron evaluables para respuesta y 16 para toxicidad (75 ciclos). Resultados: Cinco pacientes tuvieron respuestas completas y cuatro parciales para un total de nueve (66 por ciento), con una supervivencia actuarial a un año del 85 por ciento. Toxicidad: Las reacciones más frecuentes neutropenia grado 3-4 en el 18.6 por ciento de los ciclos, neutropenial febril en 2.6 por ciento, rash alérgico en dos casos y anafilaxia en una. También se observó edema con incremento de peso en seis casos y en otros tres el edema fue leve. Hubo neuropatía grado 1 en cuatro casos y grado 2 en dos pacientes. Cinco mujeres presentaron piel seca con descamación y tres enfermas exfoliación. Tres pacientes presentaron onicólisis. Se requirió ajuste de dosis en siete ciclos. Conclusiones: Nuestros resultados sugieren la gran respuesta a docetaxel como terapia de primera línea en cáncer mamario metastásico; la toxicidad más frecuente y limitante en la neutropenia y la retención de líquidos

Seguridad y eficacia del tratamiento con paclitaxel en México: reporte nacional preliminar / Safety and efficacy of treatment with paclitaxel in Mexico: a preliminary report

Antecedentes: los estudios de laboratorio sugieren que paclitaxel tiene efectos antitumorales en un número importante de tipos de células tumorales, incluyendo las líneas celulares de ovario, mama y pulmón. Objetivo: determinar los efectos antitumorales de paclitaxel en pacientes con cáncer de ovario, mama o pulmón. Material y métodos: de junio de 1997 a febrero de 1998 se trataron 146 pacientes con cáncer de ovario, mama o pulmón. El 54 por ciento había recibido radioterapia o quimioterapia. El 55 por ciento tenía neutropenia reversible grado 3 y un paciente, grado 4; 25 por ciento tenía neuropatía periférica transitoria grado 3; 21 por ciento, mialgia, y 30 por ciento, artralgia. Resultados: en 94 por ciento de los casos de cáncer de pulmón hubo respuesta objetiva en primera línea de tratamiento con duración media de respuesta de siete meses y 66 por ciento de respuesta parcial en segunda línea con duración media de respuesta de 4.6 meses. En 75 por ciento de los casos de cáncer de mama hubo respuesta objetiva en primera línea con duración media de respuesta de ocho meses y 61 por ciento en segunda línea con duración media de respuesta de 5.4 meses. En 61 por ciento de los casos de cáncer de ovario hubo respuesta objetiva en primera línea con duración media de respuesta de nueve meses y 45 por ciento en segunda línea con duración media de respuesta de 6.2 meses. Conclusiones: paclitaxel es un medicamento seguro y bien tolerado. Debido a los porcentajes de respuesta observados, se necesitan estudios controlados, multicéntricos y prospectivos.