PURPOSE: In recent years, unprecedented benefits have been observed with the development of cyclin-dependent kinase (CDK) 4 and 6 inhibitors for the treatment of hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer. However, there is scarce evidence of their value in specific populations, such as patients carrying germline pathogenic variants in DNA repair–related genes. PATIENTS AND METHODS: We retrospectively studied the efficacy of CDK 4/6 inhibitors plus endocrine therapy in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer. Three cohorts were compared, including patients harboring germline pathogenic variants in DNA repair–related genes (g BRCA1/2- ATM- CHEK2 mutated), those tested without these mutations (wild type [WT]), and the nontested subgroup. Relevant prognostic factors including age, metastatic site (visceral v nonvisceral), Eastern Cooperative Oncology Group, and prior treatment with CDK 4/6 inhibitors were stratified by univariate and multivariate Cox regression models. RESULTS: Among the total population (n = 217), 15 (6.9%) patients carried g BRCA1/2 (n = 10)- ATM (n = 4)- CHEK2 (n = 1) pathogenic variants, 45 (20.7%) were WT, and 157 (72.4%) were nontested. Gene pathogenic variant carriers were younger ( P < .001). Most patients (164, 75.6%) had not received prior endocrine therapy in the advanced setting. Median progression-free survival was shorter in patients with evaluated germline pathogenic variants (10.2 months [95% CI, 5.7 to 14.7]), compared with WT and nontested patients (15.6 months [95% CI, 7.8 to 23.4], and (17.6 months [95% CI, 12.9 to 22.2]; P = .002). Consistently, a worse median overall survival was observed in the subgroup with germline pathogenic variants than in the WT group ( P = .006). Multivariable analysis showed that mutation status was an independent prognostic factor of progression-free survival ( P = .020) and overall survival ( P = .012). CONCLUSION: In this retrospective real-world study, g BRCA1/ 2- ATM-CHEK2 pathogenic variants were independently associated with poor outcomes in patients with advanced breast cancer treated with CDK4/6 inhibitors.

Background/Objectives: BRAF-mutation is a poor prognostic factor in colorectal cancer (CRC). There is a need for real-world data in low-middle-income countries regarding clinical characteristics, outcomes, and treatment strategies. This study aims to describe progression free survival (PFS) and overall survival (OS) in the first-line setting, and sequences of treatment regimens. Methods: We retrospective analyze patients from ten oncology centers in Argentina, diagnosed with BRAFV600E-mutated advanced CRC between January 2014 and July 2023. Results: A total of 161 patients with metastatic CRC and BRAFV600E-mutation. The median age was 58.5 (IQR 47-69) and 21.7% were MMR-deficient (dMMR). 93.8% of the patients received first-line treatment. With a median follow-up of 23 months (95% CI 16.5 - 33.4 months), the median OS was 20.6 months (95% CI 18.4 - 29 months) and PFS 9 months (95% CI 7.4 - 10.5 months). The most common regimen was doublet chemotherapy plus anti-VEGF in 49%. 26% received BRAF inhibitors in second line setting. Conclusions: This study represents, to the best of our knowledge, the largest published real-world cohort of BRAFV600E-mutated CRC in Latin America. The heterogeneity in treatments reflect the existence of barriers to access high-cost drugs in our country. Cooperative efforts are needed to understand the particular characteristics of this subgroup of patients.

Background/Objectives: The BRAF-mutation is a poor prognostic factor in colorectal cancer (CRC). There is a need for real-world data in low-middle-income countries regarding clinical characteristics, outcomes, and treatment strategies. This study aims to describe progression-free survival (PFS) and in the first- and second-line setting and sequences of treatment regimens. Methods: We retrospectively analyze patients from ten oncology centers in Argentina, diagnosed with BRAF^V600E-mutated advanced CRC between January 2014 and July 2023. Results: A total of 161 patients with metastatic CRC and BRAF^V600E-mutation. The median age was 58.5 (IQR 47–69), and 21.7% were MMR-deficient (dMMR). Of these patients, 93.8% received first-line treatment. With a median follow-up of 23 months (95% CI 16.5–33.4 months), the median PFS was 9 months (95% CI 7.4–10.5 months). The most common regimen in first line setting was doublet chemotherapy plus anti-VEGF for 49% of the patients. Twenty-six percent of the patients received BRAF inhibitors in the second-line setting, with a median PFS of 5.2 months (95% CI 4.9—NR); the overall response rate (ORR) was 10.5%. Conclusions: This study represents, to the best of our knowledge, the largest published real-world cohort of BRAF^V600E-mutated CRC in Latin America. The heterogeneity of the treatments reflects the existence of barriers to access to high-cost drugs in our country. Cooperative efforts are needed to understand the particular characteristics of this subgroup of patients.

Revista Oncología Clínica. Órgano de la Asociación Argentina de Oncología Clínica. - AAOC

Las opciones terapéuticas actuales para cáncer colorrectal metastásico (CCRm) incluyen quimioterapia y terapias dirigidas. Sin embargo, el uso óptimo y la secuencia de estos agentes aún no se ha determinado. Los objetivos fueron analizar retrospectivamente las características clínico-patológicas y moleculares de los pacientes con CCRm RAS WT al diagnóstico, que recibieron terapia con anti-EGFR y que fueron re-expuestos a la misma ya sea tras la progresión (rechallenge) o sin progresión e interrupción por otra causa (reintroducción). Evaluar la toxicidad, adherencia y eficacia del tratamiento en nuestra práctica diaria. Estudio retrospectivo, descriptivo y observacional. Se utilizó la base de datos institucional de los pacientes con diagnóstico de CCRm desde enero 2007 a septiembre 2020 del Instituto Alexander Fleming, del Hospital Udaondo y la Fundación Favaloro. Se analizaron 18 pacientes. La localización del tumor primario fue: 17% (n:3) tumor derecho, 83% (n:15) tumor izquierdo. Todos los pacientes eran triple wild-type (KRAS-NRAS-BRAF). El 6% (n:1) tenía dMMR y HER+++ por inmunohistoquímica. El 67% (n:12) recibió tratamiento combinado con anti-VEGF previo al rechallenge/reintroducción anti-EGFR y 33% (n:6) no recibió anti-VEGF previo al rechallenge/reintroducción anti-EGFR. La SLP a la primera línea con anti-EGFR fue de 11 meses (rango 4.7-49.7 meses). El 78% (n:14) realizó reintroducción y 22% (n:4) realizó rechallenge a la terapia con anti-EGFR. La supervivencia libre de progresión en reintroducción fue de 6.1 meses (rango 1.3-11.6 meses) y en rechallenge fue de 6 meses (rango 4.9-17.3 meses). La supervivencia global mediana en los pacientes con rechallenge/reintroducción fue de 13.6 meses (rango 1.4-41 meses).

Introducción: El cáncer colorrectal (CCR) en adultos jóvenes es una entidad cada vez más prevalente y se estima que en la próxima década 1 de cada 4 pacientes sea menor de 50 años. En nuestro país existen pocos datos de este subgrupo de pacientes. Métodos: Estudio de cohorte retrospectivo, de pacientes atendidos en nuestra institución, con CCR confirmados histológicamente, desde enero 2018 a junio 2023 y con menos de 50 años al momento del diagnóstico. El objetivo primario fue describir las características clínico-patológicas y moleculares en 3 subgrupos: 40-49, 30-39 y ≤ 29 años. Los objetivos secundarios fueron tiempo al diagnóstico, sobrevida global y sobrevida libre de progresión en los distintos subgrupos. Resultados: Se incluyeron 502 pacientes con histología de adenocarcinoma. El 59.8% tenía 40-49 años, 34.8% 30-39 años y 5.4% ≤ 29 años al momento del diagnóstico. Estadios tempranos (61.3%, 57.1% y 59.3%) y localización derecha (22%, 22.8% y 22.2%) fueron similares en los subgrupos. El sexo femenino fue el más prevalente, siendo mayor en ≤ 29 años (59.3%). El estatus de MMR se pudo determinar en el 69.2% y el déficit de proteínas de MMR (MMRd) fue comparable entre los subgrupos, con porcentajes de 8%, 11.4% y 11.1%, respectivamente. Mutaciones germinales fueron encontradas en un 20% de los pacientes.