Subpopulation treatment effect pattern plot analysis: a prognostic model for distant recurrence-free survival to estimate delayed adjuvant chemotherapy initiation effect in triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) is a heterogeneous disease associated with a poor prognosis. Delaying in time to start adjuvant chemotherapy (TTC) has been related to an increased risk of distant recurrence-free survival (DRFS). We aimed to develop a prognostic model to estimate the effects of delayed TTC among TNBC risk subgroups. Materials and methods: We analyzed 687 TNBC patients who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). Database was randomly divided to create a discovery set (n=344) and a validation set (n=343). Univariate and multivariate Cox regression models were performed to identify prognostic factors for DRFS. Risk stratification was implemented through two models developed based on proportional hazard ratios from significant clinicopathological characteristics. Subpopulation treatment effect pattern plot (STEPP) analysis was performed to determine the best prognostic cut-off points for stratifying TNBC subgroups according to risk scores and estimate Kaplan-Meier differences in 10-year DRFS comparing TTC (≤30 vs.>30 days). Results: In univariate analysis, patients aged ≥70 years (HR=4.65; 95% CI: 2.32-9.34; p=<0.001), those at stages pT3-T4 (HR=3.28; 95% CI: 1.57-6.83; p=0.002), and pN2-N3 (HR=3.00; 95% CI: 1.90-4.76; p=<0.001) were notably associated with higher risk. STEPP analysis defined three risk subgroups for each model. Model N°01 categorized patients into low (score: 0-31), intermediate (score:32-64), and high-risk (score: 65-100) cohorts; meanwhile, Model N°02: low (score: 0-26), intermediate (score: 27-55), and high (score: 56-100). Kaplan-Meier plots showed that in the discovery set, patients with TTC>30 days experienced a 17.5% decrease in 10-year DRFS rate (95%CI=6.7-28.3), and the impact was more remarkable in patients who belong to the high-risk subgroup (53.3% decrease in 10 years-DRFS rate). Similar results were found in the validation set. Conclusions: We developed two prognostic models based on age, pT, and pN to select the best one to classify TNBC. For Model N°02, delayed adjuvant chemotherapy conferred a higher risk of relapse in patients ≥70 years and who were characterized by pT3/T4 and pN2/N3. Thus, more efforts should be considered to avoid delayed TTC in TNBC patients, especially those in high-risk subgroups.

Real-world outcomes of anti-EGFR therapy in advanced non-small cell lung cancer EGFR mutated in Peru.

BACKGROUND: Despite the advances in the management of advanced non-small cell lung cancer (NSCLC), the access to genetic profiling and target therapies remains a challenge in Latin America, even in countries with a higher rate of targetable mutations. The aim of this study is to evaluate the clinical outcomes of anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) treatment in a Peruvian real-world setting. METHODS: This is a retrospective study of recurrent or advanced NSCLC EGFR mutated patients diagnosed and treated with anti-EGFR TKI at Instituto Nacional de Enfermedades Neoplásicas (INEN) between January 1, 2015 to December 31, 2020. The outcomes were objective response rate (ORR), progression free survival (PFS), and overall survival (OS). RESULTS: We identify 613 stage IV or recurrent NSCLC patients who were tested for EGFR mutations and found a pathogenic mutation in 39.5% of patients. Only 51.2% of them received anti-EGFR TKI as institutional treatment. ORR was 58%, after median follow-up of 32 months, the estimated median PFS was 13.9 months (11.1-16.7 months), and the estimated median OS was 21.7 months (18.5-24.9 months). No differences were found in PFS according to line of treatment or brain metastases at diagnosis (p = 0.46 and p = 0.07, respectively), respect to OS there were no differences line of treatment (p = 0.12), significant difference were found in presence of brain metastases (p = 0.006). CONCLUSION: Our study demonstrates that erlotinib for advanced NSCLC harboring EGFR-activating mutations is effective even in patients usually excluded from clinical trial, like those previously exposed to one or more lines of chemotherapy or with brain metastases.

Streamlining breast cancer and colorectal cancer biosimilar regulations to improve treatment access in Latin America: an expert panel perspective.

In a multiday conference, a panel of Latin American experts in biological cancer therapies and health economics were provided with questions to address the barriers restricting access to biosimilars in Latin America, specifically for patients with breast cancer and colorectal cancer, for whom biosimilars can be a path forward to increasing access to care. During the conference, responses were discussed and edited until a consensus was achieved. The regulatory challenges identified in the conference included heterogenous regulations, non-adherence to regulatory pathways, scarcity of market opportunity, inadequate naming of biosimilars by only using international non-proprietary names, imprecise use of interchangeability and substitution, and insufficient traceability and pharmacovigilance. Recommendations were developed to improve the implementation of regulatory pathways and reliable procurement strategies that increase access to these therapies with adequate traceability and outcome measures; efforts from all involved stakeholders will be crucial. These recommendations can serve as a strategy for biosimilar adoption in other countries in a similar situation.

[Clinical-pathological features and survival in young women with cervical cancer: a retrospective analysis from the instituto nacional de enfermedades neoplásicas]. / Características clínico-patológicas y sobrevida en mujeres jóvenes con cáncer cervical: análisis retrospectivo del instituto nacional de enfermedades neoplásicas.

OBJECTIVE: To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. MATERIALS AND METHODS: Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. RESULTS: 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. CONCLUSIONS: Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosis- related factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.

OBJETIVOS: Determinar las características clínicas, histológicas y los factores pronósticos del cáncer cervical (CC) en pacientes jóvenes peruanas. MATERIALES Y MÉTODOS: Análisis retrospectivo de pacientes de 35 años de edad o menos diagnosticadas con CC entre el 2008 y el 2012 en el Instituto Nacional de Enfermedades Neoplásicas. RESULTADOS: 449 pacientes tenían neoplasias epiteliales. Los tipos histológicos principales fueron: carcinoma de células escamosas (84,9%), adenocarcinoma (11,0%) y carcinoma adenoescamoso (2,4%). El tamaño tumoral promedio fue 4,98 cm. También se identificó anemia (55,7%), creatinina elevada (21,2%) e hidronefrosis (13,8%). El 82,3% de los pacientes presentaron enfermedad localmente avanzada. Los estadios IIB (47,4%) y IIIB (25,8%) fueron los más comunes. La supervivencia global a 5 años fue de 59,5% (I, 90,9%; II, 57,5%; III, 42,7% y IV, 13,3%). La creatinina elevada, la anemia, el tamaño tumoral, el compromiso parametrial y la hidronefrosis fueron factores que afectaron la supervivencia. No se encontró relación significativa entre el tipo histológico y la supervivencia. La presencia de anemia (Hazard Ratio ajustado [HRa]: 2,5; intervalo de confianza al 95% [IC 95%]: 1,6-4,0) y la hidronefrosis (HRa: 1,6; IC 95%: 1,0-4,0) estuvieron independientemente asociados con la supervivencia; asimismo, el compromiso parametrial con (HRa: 3,3; IC 95%: 1,5-7,2) o sin (HRa: 2,6; IC 95%: 1,3-5,3) extensión al hueso pélvico. CONCLUSIONES: El cáncer cervical en jóvenes peruanas es diagnosticado en estadios avanzados. La supervivencia global en cada estadio es similar a la reportada en pacientes mayores. Se confirmó la importancia de los factores convencionales relacionados con el pronóstico. La anemia fue un factor de pronóstico independiente importante que requiere mayores investigaciones.

Características clínico-patológicas y sobrevida en mujeres jóvenes con cáncer cervical: análisis retrospectivo del instituto nacional de enfermedades neoplásicas / Clinical-pathological features and survival in young women with cervical cancer: a retrospective analysis from the instituto nacional de enfermedades neoplásicas

RESUMEN Objetivos Determinar las características clínicas, histológicas y los factores pronósticos del cáncer cervical (CC) en pacientes jóvenes peruanas. Materiales y métodos Análisis retrospectivo de pacientes de 35 años de edad o menos diagnosticadas con CC entre el 2008 y el 2012 en el Instituto Nacional de Enfermedades Neoplásicas. Resultados 449 pacientes tenían neoplasias epiteliales. Los tipos histológicos principales fueron: carcinoma de células escamosas (84,9%), adenocarcinoma (11,0%) y carcinoma adenoescamoso (2,4%). El tamaño tumoral promedio fue 4,98 cm. También se identificó anemia (55,7%), creatinina elevada (21,2%) e hidronefrosis (13,8%). El 82,3% de los pacientes presentaron enfermedad localmente avanzada. Los estadios IIB (47,4%) y IIIB (25,8%) fueron los más comunes. La supervivencia global a 5 años fue de 59,5% (I, 90,9%; II, 57,5%; III, 42,7% y IV, 13,3%). La creatinina elevada, la anemia, el tamaño tumoral, el compromiso parametrial y la hidronefrosis fueron factores que afectaron la supervivencia. No se encontró relación significativa entre el tipo histológico y la supervivencia. La presencia de anemia (Hazard Ratio ajustado [HRa]: 2,5; intervalo de confianza al 95% [IC 95%]: 1,6-4,0) y la hidronefrosis (HRa: 1,6; IC 95%: 1,0-4,0) estuvieron independientemente asociados con la supervivencia; asimismo, el compromiso parametrial con (HRa: 3,3; IC 95%: 1,5-7,2) o sin (HRa: 2,6; IC 95%: 1,3-5,3) extensión al hueso pélvico. Conclusiones El cáncer cervical en jóvenes peruanas es diagnosticado en estadios avanzados. La supervivencia global en cada estadio es similar a la reportada en pacientes mayores. Se confirmó la importancia de los factores convencionales relacionados con el pronóstico. La anemia fue un factor de pronóstico independiente importante que requiere mayores investigaciones.

ABSTRACT Objective To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. Materials and methods Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. Results 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. Conclusions Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosis- related factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.