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  1. Article ; Online: Molecular Tumor Board Improves Outcomes for Hispanic Patients With Advanced Solid Tumors.

    Sotelo-Rodríguez, Carolina / Vallejo-Ardila, Dora / Ruiz-Patiño, Alejandro / Chamorro, Diego F / Rodríguez, July / Moreno-Pérez, Darwin A / Carranza, Hernán / Otero, Jorge / Vargas, Carlos / Archila, Pilar / Rojas, Leonardo / Zuluaga, Jairo / Rubio, Cladelis / Ordóñez-Reyes, Camila / Garcia-Robledo, Juan Esteban / Mejía, Sergio / Jaller, Elvira / Arrieta, Oscar / Cardona, Andrés F

    JCO global oncology

    2024  Volume 10, Page(s) e2300011

    Abstract: Purpose: Multidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in ... ...

    Abstract Purpose: Multidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in developing countries. Herein, we describe the possible benefits and limitations of the first MTB established in Colombia.
    Methods: Demographic, clinical, and genomic information was collected between August 2020 and November 2021. By mid-2020, an MTB strategy was created to discuss clinical cases with one or more genomic alterations identified by next-generation sequencing using an open-access virtual platform. We characterized the patient population as benefiting from the recommended treatment option. We assessed the benefits and access to available targeted therapies that have the potential to change clinical management by making recommendations to treating oncologists on the basis of genomic profiling. However, we did not assess the treatment oncologists' compliance with MTB recommendations because they were not intended to replace clinical judgment/standard of care.
    Results: A total of 146 patients were included in the discussions of the MTB. The median age was 59 years, and 59.6% were women. Genomic results prompting a change in therapeutic decisions were obtained in 53.1% of patients (95% CI, 44.9 to 61.3). The most prevalent malignancy was non-small-cell lung cancer (51%). Other malignancies represented 60%, 50%, and 30% of patients with soft-tissue sarcomas, brain tumors, and breast cancer, respectively.
    Conclusion: Using an open-access virtual platform, MTBs were feasible in low- and middle-income countries on the basis of the capability to provide the benefits and access to available targeted therapies that are not standard of care. Furthermore, MTB recommendations were made available to the treating oncologist in different locations across Colombia, providing the option to modify clinical management in most of these patients.
    MeSH term(s) Female ; Humans ; Male ; Middle Aged ; Breast Neoplasms ; Carcinoma, Non-Small-Cell Lung ; Hispanic or Latino ; Lung Neoplasms ; Medical Oncology ; Sarcoma ; Brain Neoplasms ; Soft Tissue Neoplasms ; Neoplasms/therapy ; Treatment Outcome ; Outcome Assessment, Health Care
    Language English
    Publishing date 2024-01-18
    Publishing country United States
    Document type Journal Article
    ISSN 2687-8941
    ISSN (online) 2687-8941
    DOI 10.1200/GO.23.00011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: KRAS and MET in non-small-cell lung cancer: two of the new kids on the 'drivers' block.

    Garcia-Robledo, Juan Esteban / Rosell, Rafael / Ruíz-Patiño, Alejandro / Sotelo, Carolina / Arrieta, Oscar / Zatarain-Barrón, Lucia / Ordoñez, Camila / Jaller, Elvira / Rojas, Leonardo / Russo, Alessandro / de Miguel-Pérez, Diego / Rolfo, Christian / Cardona, Andrés F

    Therapeutic advances in respiratory disease

    2022  Volume 16, Page(s) 17534666211066064

    Abstract: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, and therapeutic management has advanced to identify various critical oncogenic mutations that promote lung cancer tumorigenesis. Subsequent studies have developed targeted therapies against ... ...

    Abstract Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, and therapeutic management has advanced to identify various critical oncogenic mutations that promote lung cancer tumorigenesis. Subsequent studies have developed targeted therapies against these oncogenes in the hope of personalized treatment based on the tumor's molecular genomics. This review presents a comprehensive review of the biology, new therapeutic interventions, and resistance patterns of two well-defined subgroups, tumors with KRAS and MET alterations. We also discuss the status of molecular testing practices for these two key oncogenic drivers, considering the progressive introduction of next-generation sequencing (NGS) and RNA sequencing in regular clinical practice.
    MeSH term(s) Biomarkers, Tumor/genetics ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Mutation ; Proto-Oncogene Proteins c-met ; Proto-Oncogene Proteins p21(ras)/genetics
    Chemical Substances Biomarkers, Tumor ; KRAS protein, human ; MET protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2022-01-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2476459-0
    ISSN 1753-4666 ; 1753-4658
    ISSN (online) 1753-4666
    ISSN 1753-4658
    DOI 10.1177/17534666211066064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP).

    Raez, Luis E / Arrieta, Oscar / Chamorro, Diego F / Soberanis-Piña, Pamela Denisse / Corrales, Luis / Martín, Claudio / Cuello, Mauricio / Samtani, Suraj / Recondo, Gonzalo / Mas, Luis / Zatarain-Barrón, Zyanya Lucia / Ruíz-Patiño, Alejandro / García-Robledo, Juan Esteban / Ordoñez-Reyes, Camila / Jaller, Elvira / Dickson, Franco / Rojas, Leonardo / Rolfo, Christian / Rosell, Rafael /
    Cardona, Andrés F

    Frontiers in oncology

    2022  Volume 12, Page(s) 904800

    Abstract: Objectives: To compare the rate disparity between outcomes (overall survival (OS), progression-free survival (PFS), and safety) of concurrent chemoradiation (cCRT) followed by durvalumab in two patient cohorts with locally advanced (LA) stage III non- ... ...

    Abstract Objectives: To compare the rate disparity between outcomes (overall survival (OS), progression-free survival (PFS), and safety) of concurrent chemoradiation (cCRT) followed by durvalumab in two patient cohorts with locally advanced (LA) stage III non-small cell lung cancer (NSCLC), one non-Hispanic White (NHW), and the other Latin-American.
    Methods: A multicenter retrospective study was performed, including 80 Hispanic and 45 NHW LA stage III NSCLC patients treated with cCRT followed by durvalumab. Both cohorts were analyzed in terms of main outcomes (OS, PFS, and safety) and compared between them and with the PACIFIC trial population outcomes. The efficacy-effectiveness gap was assessed using an efficacy-effectiveness (EE) factor that was calculated by dividing each cohort median overall survival by the corresponding reference OS from the PACIFIC trial. In both cohorts, results of PD-L1 testing were recorded, and the main outcomes were compared according to PD-1 expression levels (≥50%, 1-49%, and <1%).
    Results: For the entire population (N=125), the overall response rate (ORR) was 57.6% (N=72), and 18.4% (N=25) achieved stable disease. OS was 26.3 months (95%CI 23.9-28.6), and PFS was 20.5 months (95%CI 18.0-23.0). PFS assessed by ethnicity showed a median for the Hispanic population of 19.4 months (95%CI 16.4-22.5) and 21.2 months (95%CI 17.2-23.3; p=0.76) for the NHW group. OS by race showed a significant difference in favor of the NHW group, with a median OS of 27.7 months (95%CI 24.6-30.9) vs. 20.0 months (95%CI 16.4-23.5) for Hispanics. (P=0.032). Unadjusted 12-month and 24-month OS was 86.6% (95%CI 79.9-88.0) and 46.6% (95%CI 40.2-48.3) for NHW compared to 82.5% (95%CI 77.1-84.2) and 17.5% (95%CI 15.6-24.5) in Hispanics. NHW had an EE factor of 0.78 and Hispanics had 0.58, showing a reduction in survival versus NHW and PACIFIC of 20% and 42%, respectively. HR for the OS among NHWs and Hispanics was 1.53 (95%CI 1.12-1.71; P=0.052) and 2.31 (95%CI 1.76-2.49; P=0.004). Fifty-six patients (44.8%) had some degree of pneumonitis due to cCRT plus durvalumab. There was no difference in the proportion of pneumonitis according to race (P=0.95), and the severity of pneumonitis was not significantly different between Hispanics and NHWs (P=0.41).
    Conclusions: Among patients with LA stage III NSCLC, NHW had better survival outcomes when compared to Hispanics, with an OS that seems to favor the NHW population and with an EE factor that shows a shorter survival in Hispanics compared with NHW and with the PACIFIC trial group.
    Language English
    Publishing date 2022-07-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.904800
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Genomic Landscape of Primary Resistance to Osimertinib Among Hispanic Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC): Results of an Observational Longitudinal Cohort Study.

    Chamorro, Diego F / Cardona, Andrés F / Rodríguez, July / Ruiz-Patiño, Alejandro / Arrieta, Oscar / Moreno-Pérez, Darwin A / Rojas, Leonardo / Zatarain-Barrón, Zyanya Lucia / Ardila, Dora V / Viola, Lucia / Recondo, Gonzalo / Blaquier, Juan B / Martín, Claudio / Raez, Luis / Samtani, Suraj / Ordóñez-Reyes, Camila / Garcia-Robledo, Juan Esteban / Corrales, Luis / Sotelo, Carolina /
    Ricaurte, Luisa / Cuello, Mauricio / Mejía, Sergio / Jaller, Elvira / Vargas, Carlos / Carranza, Hernán / Otero, Jorge / Archila, Pilar / Bermudez, Maritza / Gamez, Tatiana / Russo, Alessandro / Malapelle, Umberto / de Miguel Perez, Diego / de Lima, Vladmir C Cordeiro / Freitas, Helano / Saldahna, Erick / Rolfo, Christian / Rosell, Rafael

    Targeted oncology

    2023  Volume 18, Issue 3, Page(s) 425–440

    Abstract: Background: Epidermal growth factor receptor (EGFR) mutations (EGFRm) represent one of the most common genomic alterations identified among patients with non-small cell lung cancer (NSCLC). Several targeted agents for patients with EGFRm have been ... ...

    Abstract Background: Epidermal growth factor receptor (EGFR) mutations (EGFRm) represent one of the most common genomic alterations identified among patients with non-small cell lung cancer (NSCLC). Several targeted agents for patients with EGFRm have been proven safe and effective, including the third-generation tyrosine kinase inhibitor (TKI) osimertinib. Nonetheless, some patients will present with or develop EGFR-TKI resistance mechanisms.
    Objective: We characterized the genomic landscape of primary resistance to osimertinib among Hispanic patients with EGFR-mutant NSCLC.
    Methods: An observational longitudinal cohort study was conducted with two groups of patients, those with intrinsic resistance (cohort A) and those with long-term survival (cohort B). All patients were treated and followed between January 2018 and May 2022. All patients were assessed for Programmed Cell Death Ligand 1 (PD-L1) expression and Bcl-2-like protein 11 (BIM)/AXL mRNA expression before starting TKI. After 8 weeks of treatment, a liquid biopsy was performed to determine the presence of circulating free DNA (cfDNA), and next-generation sequencing (NGS) was used to identify mutations at the time of progression. In both cohorts, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated.
    Results: We found a homogeneous distribution of EGFR-sensitizing mutations in both cohorts. For cohort A, exon 21 mutations were more common than exon 19 deletions (ex19dels) for cohort B (P = 0.0001). The reported ORR for osimertinib was 6.3% and 100% for cohorts A and B, respectively (P = 0.0001). PFS was significantly higher in cohort B (27.4 months vs. 3.1 months; P = 0.0001) and ex19del patients versus L858R (24.5 months, 95% confidence interval [CI] 18.2-NR), vs. 7.6 months, 95% CI 4.8-21.1; P = 0.001). OS was considerably lower for cohort A (20.1 months vs. 36.0 months; P = 0.0001) and was better for patients with ex19del, no brain metastasis, and low tumor mutation burden. At the time of progression, more mutations were found in cohort A, identifying off-target alterations more frequently, including TP53, RAS, and RB1.
    Conclusion: EGFR-independent alterations are common among patients with primary resistance to osimertinib and significantly impact PFS and OS. Our results suggest that among Hispanic patients, other variables associated with intrinsic resistance include the number of commutations, high levels AXL mRNA, and low levels of BIM mRNA, T790M de novo, EGFR p.L858R presence, and a high tumoral mutational burden.
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Longitudinal Studies ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Mutation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Aniline Compounds/pharmacology ; Aniline Compounds/therapeutic use ; Cohort Studies ; Genomics ; Cell-Free Nucleic Acids ; Hispanic or Latino
    Chemical Substances osimertinib (3C06JJ0Z2O) ; ErbB Receptors (EC 2.7.10.1) ; Protein Kinase Inhibitors ; Aniline Compounds ; Cell-Free Nucleic Acids ; EGFR protein, human (EC 2.7.10.1)
    Language English
    Publishing date 2023-04-05
    Publishing country France
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2222136-0
    ISSN 1776-260X ; 1776-2596
    ISSN (online) 1776-260X
    ISSN 1776-2596
    DOI 10.1007/s11523-023-00955-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation.

    Cardona, Andrés F / Jaramillo-Velásquez, Daniel / Ruiz-Patiño, Alejandro / Polo, Carolina / Jiménez, Enrique / Hakim, Fernando / Gómez, Diego / Ramón, Juan Fernando / Cifuentes, Hernando / Mejía, Juan Armando / Salguero, Fernando / Ordoñez, Camila / Muñoz, Álvaro / Bermúdez, Sonia / Useche, Nicolas / Pineda, Diego / Ricaurte, Luisa / Zatarain-Barrón, Zyanya Lucia / Rodríguez, July /
    Avila, Jenny / Rojas, Leonardo / Jaller, Elvira / Sotelo, Carolina / Garcia-Robledo, Juan Esteban / Santoyo, Nicolas / Rolfo, Christian / Rosell, Rafael / Arrieta, Oscar

    Journal of neuro-oncology

    2021  Volume 154, Issue 3, Page(s) 353–364

    Abstract: Background: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors or antibodies has shown limited efficacy. ...

    Abstract Background: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer.
    Methods: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial next-generation sequencing panel in liquid biopsy.
    Results: There were ten males (66.7%), and the median patient's age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR.
    Conclusions: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.
    MeSH term(s) Acrylamides ; Adult ; Aged ; Aniline Compounds ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/therapeutic use ; Carcinoma, Non-Small-Cell Lung ; ErbB Receptors/genetics ; Female ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Humans ; Lung Neoplasms ; Male ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local ; Protein Kinase Inhibitors ; Retrospective Studies
    Chemical Substances Acrylamides ; Aniline Compounds ; Protein Kinase Inhibitors ; epidermal growth factor receptor VIII ; Bevacizumab (2S9ZZM9Q9V) ; osimertinib (3C06JJ0Z2O) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2021-09-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604875-4
    ISSN 1573-7373 ; 0167-594X
    ISSN (online) 1573-7373
    ISSN 0167-594X
    DOI 10.1007/s11060-021-03834-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP).

    Cordeiro de Lima, Vladmir C / Corassa, Marcelo / Saldanha, Erick / Freitas, Helano / Arrieta, Oscar / Raez, Luis / Samtani, Suraj / Ramos, Maritza / Rojas, Carlos / Burotto, Mauricio / Chamorro, Diego F / Recondo, Gonzalo / Ruiz-Patiño, Alejandro / Más, Luis / Zatarain-Barrón, Lucia / Mejía, Sergio / Nicolas Minata, José / Martín, Claudio / Bautista Blaquier, Juan /
    Motta Guerrero, Rodrigo / Aliaga-Macha, Carlos / Carracedo, Carlos / Ordóñez-Reyes, Camila / Garcia-Robledo, Juan Esteban / Corrales, Luis / Sotelo, Carolina / Ricaurte, Luisa / Santoyo, Nicolas / Cuello, Mauricio / Jaller, Elvira / Rodríguez, July / Archila, Pilar / Bermudez, Maritza / Gamez, Tatiana / Russo, Alessandro / Viola, Lucia / Malapelle, Umberto / de Miguel Perez, Diego / Rolfo, Christian / Rosell, Rafael / Cardona, Andrés F

    Lung cancer (Amsterdam, Netherlands)

    2022  Volume 170, Page(s) 114–121

    Abstract: Background: Mutations in STK11 (STK11: 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) ... ...

    Abstract Background: Mutations in STK11 (STK11
    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 STK11
    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 KRAS
    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.
    MeSH term(s) AMP-Activated Protein Kinase Kinases ; B7-H1 Antigen/genetics ; Biomarkers, Tumor/genetics ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Hispanic or Latino/genetics ; Humans ; Kelch-Like ECH-Associated Protein 1/genetics ; Lung Neoplasms/pathology ; Mutation ; NF-E2-Related Factor 2/genetics ; Prognosis ; Protein Serine-Threonine Kinases/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; Registries ; Retrospective Studies
    Chemical Substances B7-H1 Antigen ; Biomarkers, Tumor ; KEAP1 protein, human ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2 ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; STK11 protein, human (EC 2.7.11.1) ; AMP-Activated Protein Kinase Kinases (EC 2.7.11.3) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2022-06-20
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 632771-0
    ISSN 1872-8332 ; 0169-5002
    ISSN (online) 1872-8332
    ISSN 0169-5002
    DOI 10.1016/j.lungcan.2022.06.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP).

    Cardona, Andrés F / Ruiz-Patiño, Alejandro / Recondo, Gonzalo / Martín, Claudio / Raez, Luis / Samtani, Suraj / Minata, José Nicolas / Blaquier, Juan Bautista / Enrico, Diego / Burotto, Mauricio / Ordóñez-Reyes, Camila / Chamorro, Diego F / Garcia-Robledo, Juan Esteban / Corrales, Luis / Zatarain-Barrón, Zyanya Lucia / Más, Luis / Sotelo, Carolina / Ricaurte, Luisa / Santoyo, Nicolas /
    Cuello, Mauricio / Mejía, Sergio / Jaller, Elvira / Vargas, Carlos / Carranza, Hernán / Otero, Jorge / Rodríguez, July / Archila, Pilar / Bermudez, Maritza / Gamez, Tatiana / Cordeiro de Lima, Vladmir / Freitas, Helano / Russo, Alessandro / Polo, Carolina / Malapelle, Umberto / Perez, Diego de Miguel / Rolfo, Christian / Viola, Lucia / Rosell, Rafael / Arrieta, Oscar

    Clinical lung cancer

    2022  Volume 23, Issue 6, Page(s) 522–531

    Abstract: Introduction: Osimertinib is a third generation EGFR-TKI inhibitor approved in the first-line setting for patients with advanced non-small cell lung cancer (NSCLC). Additionally, it represents the treatment of choice in patients who present with T790M ... ...

    Abstract Introduction: Osimertinib is a third generation EGFR-TKI inhibitor approved in the first-line setting for patients with advanced non-small cell lung cancer (NSCLC). Additionally, it represents the treatment of choice in patients who present with T790M mutations and evidence of relapse of the disease. Effectiveness and safety of this drug have been studied in multiple clinical trials and observational studies, however, information regarding outcomes among Hispanic patients treated with Osimertinib is scarce. The objective of this study was to examine real-world effectiveness and safety of first-line Osimertinib in a cohort of Hispanic patients with NSCLC, emphasizing post-progression outcomes.
    Methods: This is a multicenter, multinational, retrospective cohort study of Hispanic patients treated with Osimertinib as first-line for EGFR-mutated NSCLC. Patients with a confirmed diagnosis of metastatic EGFR-mutated NSCLC who received Osimertinib (80mg/day until evidence of disease progression or presence of intolerable adverse effects) were identified and included. NGS was performed in tumor samples or liquid biopsies among patients who had disease progression. The primary outcome was progression-free survival, and the secondary outcome was post-progression survival.
    Results: A total of 94 patients from Mexico, Argentina, Costa Rica, Colombia, Panama, Chile and the USA were included, with a median age of 59 years. Identified mutations included EGFR Exon 19 deletions and EGFR pL858R point mutations. Median progression-free survival (PFS) was 14.4 months (95%CI 12.4-18.2 months). Lung/pleura and lymph nodes were the most common sites of progression. Median post-progression survival was 7.73 months (95%CI 4.07 months-Not reached). Factors which negatively affected PFS included presence of liver metastases at diagnosis and a tumor mutational burden > 5 mut/Mb.
    Conclusion: Treatment with first line osimertinib represents an effective and safe option for Hispanic patients with metastatic NSCLC. Liver metastases and a higher tumor mutation burden were associated with a lower PFS. Despite effectiveness, different mechanisms of resistance were identified among the patients in this cohort, including mutations which can be targeted by other therapeutic options.
    MeSH term(s) Acrylamides ; Aniline Compounds ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Disease Progression ; Drug Resistance, Neoplasm ; ErbB Receptors/genetics ; Hispanic or Latino ; Humans ; Indoles ; Liver Neoplasms/drug therapy ; Liver Neoplasms/secondary ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Middle Aged ; Mutation/genetics ; Neoplasm Recurrence, Local/drug therapy ; Protein Kinase Inhibitors/pharmacology ; Pyrimidines ; Retrospective Studies
    Chemical Substances Acrylamides ; Aniline Compounds ; Indoles ; Protein Kinase Inhibitors ; Pyrimidines ; osimertinib (3C06JJ0Z2O) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2022-06-06
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2145146-1
    ISSN 1938-0690 ; 1525-7304
    ISSN (online) 1938-0690
    ISSN 1525-7304
    DOI 10.1016/j.cllc.2022.06.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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