Browsing by Author "Motta-Guerrero, R"

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A high number of co-occurring genomic alterations detected by NGS is associated with worse clinical outcomes in advanced EGFR-mutant lung adenocarcinoma: Data from LATAM population
(Elsevier Ireland Ltd, 2022) Heredia, D; Mas, L; Cardona, AF; Oyervides, V; Motta-Guerrero, R; Galvez-Nino, M; Lara-Mejía, L; Aliaga-Macha, C; Carracedo, C; Varela-Santoyo, E; Ramos-Ramírez, M; Davila-Dupont, D; Martínez, J; Cruz-Rico, G; Remon, J; Arrieta, O
Background: Co-occurring genomic alterations identified downstream main oncogenic drivers have become more evident since the introduction of next-generation sequencing (NGS) analyses at diagnosis and progression. Emerging evidence has stated that co-occurring genomic alterations at diagnosis might represent de novo and primary resistance mechanisms to tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant (EGFRm) non-small lung cancer (NSCLC). In this study, we assessed the prognostic role of co-occurring genomic alterations in advanced EGFRm NSCLC. Methods: A cohort of 111 patients with advanced NSCLC harboring EGFR-sensitive mutations detected by PCR was analyzed in 5 Latin American oncological centers from January 2019 to December 2020. All eligible patients received upfront therapy with EGFR-TKI. Co-occurring genomic alterations were determined at diagnosis in every patient by the NGS (FoundationOneCDx) comprehensive platform, which evaluates 324 known cancer-related genes. Results: EGFR exon19 deletion was the most frequent oncogenic driver mutation (60.4 %) detected by NGS. According to the NGS assay, 31 % and 68.3 % of patients had 1–2 and ≥ 3 co-occurring genomic alterations, respectively. The most frequent co-occurring genomic alterations were TP53 mutations (64.9 %) followed by CDKN2AB alterations (13.6 %), BRCA2 (13.6 %), and PTEN (12.7 %) mutations. Baseline central nervous system disease was present in 42.7 % of patients. First- or second-generation EGFR TKIs (gefitinib, afatinib, or erlotinib) were the most common treatment in 67.5 % of patients, while osimertinib was administered in 27.9 % of cases. The median PFS in all evaluated patients was 13.63 months (95 %CI: 11.79–15.52). Using ≥ 3 co-occurring alterations as the cut-off point, patients with ≥ 3 co-occurring genomic alterations showed a median PFS, of 12.7 months (95 %CI: 9.92–15.5) vs 21.3 months (95 %CI: 13.93-NR) in patients with 2 or less co-occurring genomic alterations [HR 3.06, (95 %CI: 1.55–5.48) p = 0.0001]. Also, patients with a TP53 mutation had a shorter PFS, 13.6 (95 %CI: 10.7–15.5) vs 19.2 months (95 %CI: 12.8-NR) in wild type TP53 [HR 2.01 (95 %CI: 1.18–3.74) p = 0.12]. In the multivariate analysis, the number (≥3) of concurrent genomic alterations and ECOG PS of 2 or more were related to a significant risk factor for progression [HR 2.79 (95 %CI: 1.49–5.23) p = 0.001 and HR 2.42 (95 %CI: 1.22–4.80) p = 0.011 respectively]. Conclusion: EGFR-mutant NSCLC is not a single oncogene-driven disease in the majority of cases, harboring a higher number of co-occurring genomic alterations. This study finds the number of co-occurring genomic alterations and the presence of TP53 mutations as negative prognostic biomarkers, which confers potentially earlier resistance mechanisms to target therapy.
Perfil epidemiológico y molecular de pacientes con cáncer de pulmón en un centro oncológicoreferencialdeLima,Perú
(Medical Body of the Almanzor Aguinaga Asenjo National Hospital, 2023) Motta-Guerrero, R; Huerta-Collado, Y; Failoc-Rojas, VE; Cabezas-Orellana, DC; Garrido-Lecca, AL; Calle-Villavicencio, A; Torres-Mera, A; Valladares-Garrido, MJ; Macha, CA; Carracedo, C
Background: According to GLOBOCAN estimates, in 2020, lung cancer was the second most frequent cancer and epidemiological information is needed in Latin American countries. The objective w a s t o d e s c r i b e t h e e p i d e m i o l o g i c a l a n d m o l e c u l a r characteristics of lung cancer patients from a referral clinic in Lima, Peru. Material and methods: A retrospective cohort study was conducted to characterize the epidemiological and molecular profile of lung cancer patients attended at a referral cancer center in Peru during 2018 to 2021. Variables such as age, sex, histology, staging and mutation were reported. In the descriptive analysis, frequencies and percentages were shown for categorical variables. For numerical variables, the best measure of central tendency and dispersion was reported. Results: A total of 225 patients with a diagnosis of lung cancer were observed. EGFR gene mutation was the most frequently detected (45.3%); and within them exon 19 deletion (55.7%). The most frequent histological type was adenocarcinoma with 180 patients (85.7%). Of the total number of patients with EGFR mutation, 77.8% received treatment with a tyrosine kinase inhibitor (osimertinib, erlotinib, afatinib) and 15.9% received immunotherapy (pembrolizumab, atezolizumab, nivolumab). Conclusions: The predominant mutation was EGFR, the most frequent histologic type was adenocarcinoma and most patients received treatment with a tyrosine kinase inhibitor. © 2023 Medical Body of the Almanzor Aguinaga Asenjo National Hospital. All rights reserved.
The role of angiogenesis inhibitors associated with tyrosine kinase inhibitors in the first-line treatment for EGFR-mutated advanced lung cancer
(Elsevier Ireland Ltd, 2024) Motta-Guerrero, R; Recondo, G; Cardona, A; Corrales, L; Arnao, V; Failoc-Rojas, VE; Aliaga, C
Tyrosine kinase inhibitors (TKIs) are the standard treatment for epidermal growth factor receptor mutant (EGFRm) advanced non-small cell lung cancer (NSCLC). Combining TKIs with an angiogenesis inhibitor has shown promise in pre-clinical studies. A systematic search of clinical trials found that combining erlotinib (a first-generation TKI) with bevacizumab or ramucirumab (angiogenesis inhibitors) improved progression-free survival (PFS) in EGFRm advanced NSCLC patients compared to TKI alone. However, no significant benefit in overall survival (OS) was observed in trials. Similar efficacy was seen in patients with specific EGFR mutations. Third generation TKIs were used as second-line therapy for patients with the T790M mutation. The combination treatment was associated with a higher incidence of severe adverse events. Overall, combining erlotinib or another TKI with an angiogenesis inhibitor is a safe and effective alternative for first-line treatment in EGFRm advanced NSCLC, particularly in countries without access to osimertinib and for patients with the EGFR L858R mutation.