Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP)

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

doi:10.1016/j.cllc.2022.06.001

Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP)

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English
Pages (from-to)	522-531
Number of pages	10
Journal	Clinical Lung Cancer
Volume	23
Issue number	6
DOIs	https://doi.org/10.1016/j.cllc.2022.06.001
State	Published - Sep 2022
Externally published	Yes

Bibliographical note

Funding Information:
Andrés F. Cardona discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, and The Foundation for Clinical and Applied Cancer Research – FICMAC. Additionally, he was linked and received honoraria as an advisor, participated in speakers' bureau, and gave expert testimony to Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, and Foundation for Clinical and Applied Cancer Research – FICMAC. Oscar Arrieta reports personal fees from Pfizer, grants and individual fees from Astra Zeneca, grants, and individual fees from Boehringer-Ingelheim, personal fees from Lilly, individual fees from Merck, personal fees from Bristol Myers Squibb, grants, and personal fees from Roche, outside the submitted work. Gonzalo Recondo reports personal fees from Pfizer, Roche, Amgen, Bayer, Takeda, MSD, Merck Serono, research grants from Amgen and Janssen, outside of the submitted work. Juan Blaquier has nothing to disclose.

Funding Information:
Supported by The CLICaP and The Foundation for Clinical and Applied Cancer Research- FICMAC (Bogotá, Colombia) research grant 023-2019 .

Publisher Copyright:
© 2022

Keywords

Carcinoma
Drug resistance
EGFR mutations
Non-Small-Cell Lung Cancer
Osimertinib

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10.1016/j.cllc.2022.06.001

Cite this

Cardona, A. F., Ruiz-Patiño, A., Recondo, G., Martín, C., Raez, L., Samtani, S., Minata, J. N., Blaquier, J. B., Enrico, D., Burotto, M., Ordóñez-Reyes, C., Chamorro, D. F., Garcia-Robledo, J. E., Corrales, L., Zatarain-Barrón, Z. L., Más, L., Sotelo, C., Ricaurte, L., Santoyo, N., ... Arrieta, O. (2022). Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP). Clinical Lung Cancer, 23(6), 522-531. https://doi.org/10.1016/j.cllc.2022.06.001

@article{aee89e90858d439cb9cdd15122ca6b0d,

title = "Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP)",

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.",

keywords = "Carcinoma, Drug resistance, EGFR mutations, Non-Small-Cell Lung Cancer, Osimertinib",

author = "Cardona, {Andr{\'e}s F.} and Alejandro Ruiz-Pati{\~n}o and Gonzalo Recondo and Claudio Mart{\'i}n and Luis Raez and Suraj Samtani and Minata, {Jos{\'e} Nicolas} and Blaquier, {Juan Bautista} and Diego Enrico and Mauricio Burotto and Camila Ord{\'o}{\~n}ez-Reyes and Chamorro, {Diego F.} and Garcia-Robledo, {Juan Esteban} and Luis Corrales and Zatarain-Barr{\'o}n, {Zyanya Lucia} and Luis M{\'a}s and Carolina Sotelo and Luisa Ricaurte and Nicolas Santoyo and Mauricio Cuello and Sergio Mej{\'i}a and Elvira Jaller and Carlos Vargas and Hern{\'a}n Carranza and Jorge Otero and July Rodr{\'i}guez and Pilar Archila and Maritza Bermudez and Tatiana Gamez and {Cordeiro de Lima}, Vladmir and Helano Freitas and Alessandro Russo and Carolina Polo and Umberto Malapelle and Perez, {Diego de Miguel} and Christian Rolfo and Lucia Viola and Rafael Rosell and Oscar Arrieta",

note = "Funding Information: Andr{\'e}s F. Cardona discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, and The Foundation for Clinical and Applied Cancer Research – FICMAC. Additionally, he was linked and received honoraria as an advisor, participated in speakers' bureau, and gave expert testimony to Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, and Foundation for Clinical and Applied Cancer Research – FICMAC. Oscar Arrieta reports personal fees from Pfizer, grants and individual fees from Astra Zeneca, grants, and individual fees from Boehringer-Ingelheim, personal fees from Lilly, individual fees from Merck, personal fees from Bristol Myers Squibb, grants, and personal fees from Roche, outside the submitted work. Gonzalo Recondo reports personal fees from Pfizer, Roche, Amgen, Bayer, Takeda, MSD, Merck Serono, research grants from Amgen and Janssen, outside of the submitted work. Juan Blaquier has nothing to disclose. Funding Information: Supported by The CLICaP and The Foundation for Clinical and Applied Cancer Research- FICMAC (Bogot{\'a}, Colombia) research grant 023-2019 . Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = sep,

doi = "10.1016/j.cllc.2022.06.001",

language = "English",

volume = "23",

pages = "522--531",

journal = "Clinical Lung Cancer",

issn = "1525-7304",

publisher = "Elsevier",

number = "6",

}

Cardona, AF, Ruiz-Patiño, A, Recondo, G, Martín, C, Raez, L, Samtani, S, Minata, JN, Blaquier, JB, Enrico, D, Burotto, M, Ordóñez-Reyes, C, Chamorro, DF, Garcia-Robledo, JE, Corrales, L, Zatarain-Barrón, ZL, Más, L, Sotelo, C, Ricaurte, L, Santoyo, N, Cuello, M, Mejía, S, Jaller, E, Vargas, C, Carranza, H, Otero, J, Rodríguez, J, Archila, P, Bermudez, M, Gamez, T, Cordeiro de Lima, V, Freitas, H, Russo, A, Polo, C, Malapelle, U, Perez, DDM, Rolfo, C, Viola, L, Rosell, R & Arrieta, O 2022, 'Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP)', Clinical Lung Cancer, vol. 23, no. 6, pp. 522-531. https://doi.org/10.1016/j.cllc.2022.06.001

TY - JOUR

T1 - Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP)

AU - Cardona, Andrés F.

AU - Ruiz-Patiño, Alejandro

AU - Recondo, Gonzalo

AU - Martín, Claudio

AU - Raez, Luis

AU - Samtani, Suraj

AU - Minata, José Nicolas

AU - Blaquier, Juan Bautista

AU - Enrico, Diego

AU - Burotto, Mauricio

AU - Ordóñez-Reyes, Camila

AU - Chamorro, Diego F.

AU - Garcia-Robledo, Juan Esteban

AU - Corrales, Luis

AU - Zatarain-Barrón, Zyanya Lucia

AU - Más, Luis

AU - Sotelo, Carolina

AU - Ricaurte, Luisa

AU - Santoyo, Nicolas

AU - Cuello, Mauricio

AU - Mejía, Sergio

AU - Jaller, Elvira

AU - Vargas, Carlos

AU - Carranza, Hernán

AU - Otero, Jorge

AU - Rodríguez, July

AU - Archila, Pilar

AU - Bermudez, Maritza

AU - Gamez, Tatiana

AU - Cordeiro de Lima, Vladmir

AU - Freitas, Helano

AU - Russo, Alessandro

AU - Polo, Carolina

AU - Malapelle, Umberto

AU - Perez, Diego de Miguel

AU - Rolfo, Christian

AU - Viola, Lucia

AU - Rosell, Rafael

AU - Arrieta, Oscar

N1 - Funding Information: Andrés F. Cardona discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, and The Foundation for Clinical and Applied Cancer Research – FICMAC. Additionally, he was linked and received honoraria as an advisor, participated in speakers' bureau, and gave expert testimony to Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, and Foundation for Clinical and Applied Cancer Research – FICMAC. Oscar Arrieta reports personal fees from Pfizer, grants and individual fees from Astra Zeneca, grants, and individual fees from Boehringer-Ingelheim, personal fees from Lilly, individual fees from Merck, personal fees from Bristol Myers Squibb, grants, and personal fees from Roche, outside the submitted work. Gonzalo Recondo reports personal fees from Pfizer, Roche, Amgen, Bayer, Takeda, MSD, Merck Serono, research grants from Amgen and Janssen, outside of the submitted work. Juan Blaquier has nothing to disclose. Funding Information: Supported by The CLICaP and The Foundation for Clinical and Applied Cancer Research- FICMAC (Bogotá, Colombia) research grant 023-2019 . Publisher Copyright: © 2022

PY - 2022/9

Y1 - 2022/9

N2 - 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.

AB - 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.

KW - Carcinoma

KW - Drug resistance

KW - EGFR mutations

KW - Non-Small-Cell Lung Cancer

KW - Osimertinib

UR - http://www.scopus.com/inward/record.url?scp=85133607813&partnerID=8YFLogxK

U2 - 10.1016/j.cllc.2022.06.001

DO - 10.1016/j.cllc.2022.06.001

M3 - Article

AN - SCOPUS:85133607813

SN - 1525-7304

VL - 23

SP - 522

EP - 531

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

IS - 6

ER -

Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP)

Abstract

Bibliographical note

Keywords

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