Browsing by Author "Motta Guerrero, R"

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STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP)
(Elsevier Ireland Ltd, 2022) Cordeiro de Lima, VC; Corassa, M; Saldanha, E; Freitas, H; Arrieta, O; Raez, L; Samtani, S; Ramos, M; Rojas, C; Burotto, M; Chamorro, DF; Recondo, G; Ruiz-Patiño, A; Más López, L; Zatarain-Barrón, L; Mejía, S; Nicolas Minata, J; Martín, C; Bautista Blaquier, J; Motta Guerrero, R; Aliaga-Macha, C; Carracedo-Gonzales, C; Ordóñez-Reyes, C; Garcia-Robledo, JE; Corrales, L; Sotelo, C; Ricaurte, L; Santoyo, N; Cuello, M; Jaller, E; Rodríguez, J; Archila, P; Bermudez, M; Gamez, T; Russo, A; Viola, L; Malapelle, U; de Miguel Perez, D; Rolfo, C; Rosell, R; Cardona, AF
Background: Mutations in STK11 (STK11Mut) and, frequently co-occurring, KEAP1 mutations (KEAP1Mut) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics. Methods: This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A). All cases were treated in routine care between January 2016 and December 2021. The main objectives were to determine the association of mutations in STK11 or KEAP1 in these patients’ tumors with overall (OS) and progression-free survival (PFS), presence of KRAS mutations, tumor mutational burden (TMB), and other relevant clinical variables. To compare outcomes with a STK11Wt/KEAP1Wt population, historical data from a cohort of Hispanic patients (N = 101) treated with first-line ICI was used, matching both groups by country of origin, gender, and Programed Death-ligand 1 (PD-L1) expression level (Cohort B). Results: Most tumors had mutations only in STK11 or KEAP1 (45.6%) without KRAS co-mutation or any other genomic alteration. Besides, 35%, 8.7%, 6.8%, and 3.9% were KRASMut + STK11Mut, KRASMut + STK11Mut + KEAP1Mut, STK11Mut + KEAP1Mut, and KRASMut + KEAP1Mut, respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRASWt (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRASMut cases (p = 0.047). Tumors with KRASMut + KEAP1Mut had significantly higher median TMB when compared to other tumors (p = 0.040). For Cohort A, median PFS was 4.9 months (95%CI 4.3–5.4), slightly longer in those with KEAP1mut 6.1 months versus STK11Mut 4.7 months (p = 0.38). In the same cohort, PD-L1 expression and TMB did not influence PFS. OS was significantly longer among patients with tumors with PD-L1 ≥ 50% (30.9 months), and different from those with PD-L1 1–49% (22.0 months), and PD-L1 < 1% (12.0 months) (p = 0.0001). When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11Mut 14.2 months versus STK11Wt 27.0 months (p = 0.0001)] or KEAP1 [KEAP1Mut 12.0 months versus KEAP1Wt 24.4 months (p = 0.005)] mutations. PD-L1 expression significantly affected OS independently of the presence of mutations in STK11, KEAP1, or KRAS. TMB-H favored better OS. Conclusions: This is the first large Hispanic cohort to study the impact of STK11 and KEAP1 mutations in NSCLC patient treated with ICI. Our data suggest that mutations in the above-mentioned genes are associated with PD-L1 expression levels and poor OS.
Targeting BRAF V600E in metastatic colorectal cancer: where are we today?
(ecancer Global Foundation, 2022) Motta Guerrero, R; Arnao-Labajos, V; Lozano-Ballena, S; Aliaga-Macha, C; Sotelo-Lezama, M; Pacheco-Roman, C; Montenegro-Beltran, P; Figueroa-Torrejon, A
Colorectal cancer (CRC) is the second most frequent cause of direct cancer death worldwide. The study of the molecular state of oncogenes has predictive and prognostic value in metastatic CRC (mCRC). The B-raf proto-oncogene (BRAF) gene mutation represents the 8%-12% of all mutations in mCRC. The BRAF V600E mutation, considered the most common alteration of BRAF, corresponds to a constitutive kinase with a high activating capacity of the RAS/RAF/MEK/ERK pathway after a cascade of successive phosphorylations in the transcription of genes. BRAF V600E mutation is more prevalent in women, elderly, right-sided colon cancer and Caucasian population. Unfortunately, it is considered a poor predictive and prognosis biomarker. Patients with mCRC BRAF V600E mutated (BRAFm) are generally associated with poor response to chemotherapy and short progression-free survival and overall survival. Recently, randomised clinical trials have studied the combination of different chemotherapy regimens with angiogenic inhibitors in mCRC BRAFm. In addition, new anti-BRAF and immunotherapy agents have also been studied in this population, with positive results. The objective of this review is to acknowledge the biology and molecular pathway of BRAF, critically analyse the clinical trials and the therapy options published until today and evaluate the options of treatment according to the patient's clinical presentation.