Real-world global data on targeting epidermal growth factor receptor mutations in stage III non-small-cell lung cancer: the results of the KINDLE study

Abdul Rahman Jazieh; Huseyin Cem Onal; Daniel Shao Weng Tan; Ross A. Soo; Kumar Prabhash; Amit Kumar; Reto Huggenberger; Byoung Chul Cho

doi:10.1177/17588359221122720

Real-world global data on targeting epidermal growth factor receptor mutations in stage III non-small-cell lung cancer: the results of the KINDLE study

Abdul Rahman Jazieh, Huseyin Cem Onal, Daniel Shao Weng Tan, Ross A. Soo, Kumar Prabhash, Amit Kumar, Reto Huggenberger, Byoung Chul Cho

Department of Internal Medicine

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

Abstract

Background: Tyrosine kinase inhibitors (TKIs) are the standard of care for resectable and metastatic non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations (EGFRm). We describe the real-world practice of EGFRm testing, prevalence, treatment and outcomes in EGFRm stage III NSCLC from a multi-country, observational study. Methods: The KINDLE study retrospectively captured diagnostic information, treatments and survival outcomes in patients with stage III NSCLC from January 2013 to December 2017. Baseline characteristics and treatments were described and real-world outcomes from initial therapy were analysed using Kaplan–Meier methods. Results: A total of 3151 patients were enrolled across three regions: Asia (n = 1874), Middle East and North Africa (MENA) (n = 1046) and Latin America (LA) (n = 231). Of these, 1114 patients (35%) were tested for EGFRm (46% in Asia, 17% in MENA and 32% in LA) and EGFRm was detected in 32% of tested patients (34.3% in Asia, 20.0% in MENA and 28.4% in LA). In a multi-variate analysis, overall EGFRm patients treated with EGFR-TKI monotherapy as initial treatment, without any irradiation, had twice the risk of dying (hazard ratio: 1.983, 95% confidence interval: 1.079–3.643; p = 0.027) versus any other treatment. Finally, unresectable patients with EGFRm NSCLC who received concurrent chemoradiotherapy (cCRT) as initial therapy had longer overall survival (OS) compared with their counterparts who only received TKI monotherapy without any irradiation (48 months versus 24 months; p < 0.001). Conclusion: The KINDLE study showed that a minority of stage III NSCLC patients were tested for EGFRm. Patients with EGFRm with unresectable NSCLC had similar outcomes from cCRT as initial therapy compared with EGFR wild type with a trend in OS favouring the EGFRm group. Outcomes with EGFR-TKI monotherapy as initial therapy, without any irradiation, were worse. The ongoing LAURA study (NCT03521154) will help define the role of EGFR-TKIs in EGFRm stage III NSCLC treated with cCRT. Trial Registration: NCT03725475.

Original language	English
Journal	Therapeutic Advances in Medical Oncology
Volume	14
DOIs	https://doi.org/10.1177/17588359221122720
Publication status	Published - 2022

Bibliographical note

Funding Information:
Disclosure: ARJ reports receiving research support from AstraZeneca, Merck Sharp & Dohme, and Pfizer and travel support from Bristol-Myers Squibb and AstraZeneca. DSWT reports having advisory role and serving as consultant for Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli Lilly, and Loxo Oncology; receiving travel support and honorarium from Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, and Takeda Pharmaceuticals; and receiving research funding from Novartis, AstraZeneca, GlaxoSmithKline, Bayer, and Pfizer. RAS reports being on advisory board for Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Taiho, Takeda Pharmaceuticals, and Yuhan; and receiving research grant support from AstraZeneca and Boehringer Ingelheim. KP reports receiving research funding from Alkem Laboratories, BDR Pharmaceutics, Biocon, Dr. Reddy’s Laboratories, Fresenius Kabi, Natco Pharma, and Roche. AK reports having employment (full time) in AstraZeneca Pharma India Ltd. RH reports having employment (full time) in AstraZeneca Plc.; and stock ownership for Allogene Therapeutics, AstraZeneca, CStone Pharmaceuticals, GlaxoSmith Kline Plc, Imugene Limited, Innate Pharma, Swedish Orphan Biovitrium AB, Chinook Therapeutics, and Adaptimmune Therapeutics. BCC reports receiving research funding from Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono Pharmaceuticals, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence Corp.; having consulting role for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Ono Pharmaceuticals, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Janssen, Medpacto, and Blueprint Medicines; having stock ownership for TheraCanVac Inc., Gencurix Inc., Bridgebio Therapeutics, Kanaph Therapeutic Inc., Cyrus Therapeutics, and Interpark Bio Convergence Corp.; being on scientific advisory board for Kanaph Therapeutic Inc., Brigebio Therapeutics, Cyrus Therapeutics, and Guardant Health; serving as board of director for Gencurix Inc. and Interpark Bio Convergence Corp.; having royalty for Champions Oncology; and serving as founder for DAAN Biotherapeutics. HCO declares no conflict of interest.

Publisher Copyright:
© The Author(s), 2022.

All Science Journal Classification (ASJC) codes

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1177/17588359221122720

Cite this

@article{b0c58d2109834cdfbcba73c942cfb6fc,

title = "Real-world global data on targeting epidermal growth factor receptor mutations in stage III non-small-cell lung cancer: the results of the KINDLE study",

abstract = "Background: Tyrosine kinase inhibitors (TKIs) are the standard of care for resectable and metastatic non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations (EGFRm). We describe the real-world practice of EGFRm testing, prevalence, treatment and outcomes in EGFRm stage III NSCLC from a multi-country, observational study. Methods: The KINDLE study retrospectively captured diagnostic information, treatments and survival outcomes in patients with stage III NSCLC from January 2013 to December 2017. Baseline characteristics and treatments were described and real-world outcomes from initial therapy were analysed using Kaplan–Meier methods. Results: A total of 3151 patients were enrolled across three regions: Asia (n = 1874), Middle East and North Africa (MENA) (n = 1046) and Latin America (LA) (n = 231). Of these, 1114 patients (35%) were tested for EGFRm (46% in Asia, 17% in MENA and 32% in LA) and EGFRm was detected in 32% of tested patients (34.3% in Asia, 20.0% in MENA and 28.4% in LA). In a multi-variate analysis, overall EGFRm patients treated with EGFR-TKI monotherapy as initial treatment, without any irradiation, had twice the risk of dying (hazard ratio: 1.983, 95% confidence interval: 1.079–3.643; p = 0.027) versus any other treatment. Finally, unresectable patients with EGFRm NSCLC who received concurrent chemoradiotherapy (cCRT) as initial therapy had longer overall survival (OS) compared with their counterparts who only received TKI monotherapy without any irradiation (48 months versus 24 months; p < 0.001). Conclusion: The KINDLE study showed that a minority of stage III NSCLC patients were tested for EGFRm. Patients with EGFRm with unresectable NSCLC had similar outcomes from cCRT as initial therapy compared with EGFR wild type with a trend in OS favouring the EGFRm group. Outcomes with EGFR-TKI monotherapy as initial therapy, without any irradiation, were worse. The ongoing LAURA study (NCT03521154) will help define the role of EGFR-TKIs in EGFRm stage III NSCLC treated with cCRT. Trial Registration: NCT03725475.",

author = "Jazieh, {Abdul Rahman} and Onal, {Huseyin Cem} and Tan, {Daniel Shao Weng} and Soo, {Ross A.} and Kumar Prabhash and Amit Kumar and Reto Huggenberger and Cho, {Byoung Chul}",

note = "Funding Information: Disclosure: ARJ reports receiving research support from AstraZeneca, Merck Sharp & Dohme, and Pfizer and travel support from Bristol-Myers Squibb and AstraZeneca. DSWT reports having advisory role and serving as consultant for Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli Lilly, and Loxo Oncology; receiving travel support and honorarium from Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, and Takeda Pharmaceuticals; and receiving research funding from Novartis, AstraZeneca, GlaxoSmithKline, Bayer, and Pfizer. RAS reports being on advisory board for Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Taiho, Takeda Pharmaceuticals, and Yuhan; and receiving research grant support from AstraZeneca and Boehringer Ingelheim. KP reports receiving research funding from Alkem Laboratories, BDR Pharmaceutics, Biocon, Dr. Reddy{\textquoteright}s Laboratories, Fresenius Kabi, Natco Pharma, and Roche. AK reports having employment (full time) in AstraZeneca Pharma India Ltd. RH reports having employment (full time) in AstraZeneca Plc.; and stock ownership for Allogene Therapeutics, AstraZeneca, CStone Pharmaceuticals, GlaxoSmith Kline Plc, Imugene Limited, Innate Pharma, Swedish Orphan Biovitrium AB, Chinook Therapeutics, and Adaptimmune Therapeutics. BCC reports receiving research funding from Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono Pharmaceuticals, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence Corp.; having consulting role for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Ono Pharmaceuticals, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Janssen, Medpacto, and Blueprint Medicines; having stock ownership for TheraCanVac Inc., Gencurix Inc., Bridgebio Therapeutics, Kanaph Therapeutic Inc., Cyrus Therapeutics, and Interpark Bio Convergence Corp.; being on scientific advisory board for Kanaph Therapeutic Inc., Brigebio Therapeutics, Cyrus Therapeutics, and Guardant Health; serving as board of director for Gencurix Inc. and Interpark Bio Convergence Corp.; having royalty for Champions Oncology; and serving as founder for DAAN Biotherapeutics. HCO declares no conflict of interest. Publisher Copyright: {\textcopyright} The Author(s), 2022.",

year = "2022",

doi = "10.1177/17588359221122720",

language = "English",

volume = "14",

journal = "Therapeutic Advances in Medical Oncology",

issn = "1758-8340",

publisher = "SAGE Publications Inc.",

}

TY - JOUR

T1 - Real-world global data on targeting epidermal growth factor receptor mutations in stage III non-small-cell lung cancer

T2 - the results of the KINDLE study

AU - Jazieh, Abdul Rahman

AU - Onal, Huseyin Cem

AU - Tan, Daniel Shao Weng

AU - Soo, Ross A.

AU - Prabhash, Kumar

AU - Kumar, Amit

AU - Huggenberger, Reto

AU - Cho, Byoung Chul

N1 - Funding Information: Disclosure: ARJ reports receiving research support from AstraZeneca, Merck Sharp & Dohme, and Pfizer and travel support from Bristol-Myers Squibb and AstraZeneca. DSWT reports having advisory role and serving as consultant for Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli Lilly, and Loxo Oncology; receiving travel support and honorarium from Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, and Takeda Pharmaceuticals; and receiving research funding from Novartis, AstraZeneca, GlaxoSmithKline, Bayer, and Pfizer. RAS reports being on advisory board for Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Taiho, Takeda Pharmaceuticals, and Yuhan; and receiving research grant support from AstraZeneca and Boehringer Ingelheim. KP reports receiving research funding from Alkem Laboratories, BDR Pharmaceutics, Biocon, Dr. Reddy’s Laboratories, Fresenius Kabi, Natco Pharma, and Roche. AK reports having employment (full time) in AstraZeneca Pharma India Ltd. RH reports having employment (full time) in AstraZeneca Plc.; and stock ownership for Allogene Therapeutics, AstraZeneca, CStone Pharmaceuticals, GlaxoSmith Kline Plc, Imugene Limited, Innate Pharma, Swedish Orphan Biovitrium AB, Chinook Therapeutics, and Adaptimmune Therapeutics. BCC reports receiving research funding from Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono Pharmaceuticals, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence Corp.; having consulting role for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Ono Pharmaceuticals, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Janssen, Medpacto, and Blueprint Medicines; having stock ownership for TheraCanVac Inc., Gencurix Inc., Bridgebio Therapeutics, Kanaph Therapeutic Inc., Cyrus Therapeutics, and Interpark Bio Convergence Corp.; being on scientific advisory board for Kanaph Therapeutic Inc., Brigebio Therapeutics, Cyrus Therapeutics, and Guardant Health; serving as board of director for Gencurix Inc. and Interpark Bio Convergence Corp.; having royalty for Champions Oncology; and serving as founder for DAAN Biotherapeutics. HCO declares no conflict of interest. Publisher Copyright: © The Author(s), 2022.

PY - 2022

Y1 - 2022

N2 - Background: Tyrosine kinase inhibitors (TKIs) are the standard of care for resectable and metastatic non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations (EGFRm). We describe the real-world practice of EGFRm testing, prevalence, treatment and outcomes in EGFRm stage III NSCLC from a multi-country, observational study. Methods: The KINDLE study retrospectively captured diagnostic information, treatments and survival outcomes in patients with stage III NSCLC from January 2013 to December 2017. Baseline characteristics and treatments were described and real-world outcomes from initial therapy were analysed using Kaplan–Meier methods. Results: A total of 3151 patients were enrolled across three regions: Asia (n = 1874), Middle East and North Africa (MENA) (n = 1046) and Latin America (LA) (n = 231). Of these, 1114 patients (35%) were tested for EGFRm (46% in Asia, 17% in MENA and 32% in LA) and EGFRm was detected in 32% of tested patients (34.3% in Asia, 20.0% in MENA and 28.4% in LA). In a multi-variate analysis, overall EGFRm patients treated with EGFR-TKI monotherapy as initial treatment, without any irradiation, had twice the risk of dying (hazard ratio: 1.983, 95% confidence interval: 1.079–3.643; p = 0.027) versus any other treatment. Finally, unresectable patients with EGFRm NSCLC who received concurrent chemoradiotherapy (cCRT) as initial therapy had longer overall survival (OS) compared with their counterparts who only received TKI monotherapy without any irradiation (48 months versus 24 months; p < 0.001). Conclusion: The KINDLE study showed that a minority of stage III NSCLC patients were tested for EGFRm. Patients with EGFRm with unresectable NSCLC had similar outcomes from cCRT as initial therapy compared with EGFR wild type with a trend in OS favouring the EGFRm group. Outcomes with EGFR-TKI monotherapy as initial therapy, without any irradiation, were worse. The ongoing LAURA study (NCT03521154) will help define the role of EGFR-TKIs in EGFRm stage III NSCLC treated with cCRT. Trial Registration: NCT03725475.

AB - Background: Tyrosine kinase inhibitors (TKIs) are the standard of care for resectable and metastatic non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations (EGFRm). We describe the real-world practice of EGFRm testing, prevalence, treatment and outcomes in EGFRm stage III NSCLC from a multi-country, observational study. Methods: The KINDLE study retrospectively captured diagnostic information, treatments and survival outcomes in patients with stage III NSCLC from January 2013 to December 2017. Baseline characteristics and treatments were described and real-world outcomes from initial therapy were analysed using Kaplan–Meier methods. Results: A total of 3151 patients were enrolled across three regions: Asia (n = 1874), Middle East and North Africa (MENA) (n = 1046) and Latin America (LA) (n = 231). Of these, 1114 patients (35%) were tested for EGFRm (46% in Asia, 17% in MENA and 32% in LA) and EGFRm was detected in 32% of tested patients (34.3% in Asia, 20.0% in MENA and 28.4% in LA). In a multi-variate analysis, overall EGFRm patients treated with EGFR-TKI monotherapy as initial treatment, without any irradiation, had twice the risk of dying (hazard ratio: 1.983, 95% confidence interval: 1.079–3.643; p = 0.027) versus any other treatment. Finally, unresectable patients with EGFRm NSCLC who received concurrent chemoradiotherapy (cCRT) as initial therapy had longer overall survival (OS) compared with their counterparts who only received TKI monotherapy without any irradiation (48 months versus 24 months; p < 0.001). Conclusion: The KINDLE study showed that a minority of stage III NSCLC patients were tested for EGFRm. Patients with EGFRm with unresectable NSCLC had similar outcomes from cCRT as initial therapy compared with EGFR wild type with a trend in OS favouring the EGFRm group. Outcomes with EGFR-TKI monotherapy as initial therapy, without any irradiation, were worse. The ongoing LAURA study (NCT03521154) will help define the role of EGFR-TKIs in EGFRm stage III NSCLC treated with cCRT. Trial Registration: NCT03725475.

UR - http://www.scopus.com/inward/record.url?scp=85138681215&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85138681215&partnerID=8YFLogxK

U2 - 10.1177/17588359221122720

DO - 10.1177/17588359221122720

M3 - Article

AN - SCOPUS:85138681215

SN - 1758-8340

VL - 14

JO - Therapeutic Advances in Medical Oncology

JF - Therapeutic Advances in Medical Oncology

ER -

Real-world global data on targeting epidermal growth factor receptor mutations in stage III non-small-cell lung cancer: the results of the KINDLE study

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this