Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma

Lingzhi Hong; Whitney E. Lewis; Monique Nilsson; Sonia Patel; Susan Varghese; Melvin J. Rivera; Robyn R. Du; Pingjun Chen; Haley N. Kemp; Waree Rinsurongkawong; Simon Heeke; Amy R. Spelman; Yasir Y. Elamin; Marcelo V. Negrao; Boris Sepesi; Don L. Gibbons; J. Jack Lee; Jia Wu; Natalie I. Vokes; John V. Heymach; Jianjun Zhang; Xiuning Le

doi:10.3390/cancers14143473

Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma

Lingzhi Hong, Whitney E. Lewis, Monique Nilsson, Sonia Patel, Susan Varghese, Melvin J. Rivera, Robyn R. Du, Pingjun Chen, Haley N. Kemp, Waree Rinsurongkawong, Simon Heeke, Amy R. Spelman, Yasir Y. Elamin, Marcelo V. Negrao, Boris Sepesi, Don L. Gibbons, J. Jack Lee, Jia Wu, Natalie I. Vokes, John V. HeymachJianjun Zhang, Xiuning Le

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

4 Scopus citations

Abstract

Background: The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting. Methods: This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; n = 84), chemotherapy combined with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n = 42), and IO monotherapy (IO-mono; n = 22). Clinical progression-free survival (PFS) and overall survival (OS) were evaluated. Associations of clinical characteristics with outcomes were assessed using univariable and multi-covariate Cox Proportional Hazards regression models. Results: A total of 178 patients (median age = 63.3; 57.9% females) with a median follow-up time of 42.0 (Interquartile range: 22.9–67.8) months were enrolled. There was no significant difference in PFS between chemoIO vs. chemo groups (5.3 vs. 4.8 months, p = 0.8). Compared to the chemo group, patients who received withBev therapy trended towards better PFS (6.1 months vs. 4.8; p = 0.3; HR 0.79; 95% CI: 0.52–1.20), while patients treated with IO-mono had inferior PFS (2.2 months; p = 0.001; HR 2.22; 95% CI: 1.37–3.59). Furthermore, PD-L1 level was not associated with PFS benefit in the chemoIO group. Patients with EGFR-mutant LUAD with high PD-L1 (≥50%) had shorter PFS (5.8 months) than non-EGFR/ALK LUAD patients who received chemoIO (12.8 months, p = 0.002; HR 0.22; 95% CI: 0.08–0.56) as first-line treatment. Chemotherapy-based therapy rendered similar benefit to patients with either EGFR exon19 deletion vs. L858R in the LUAD. Conclusions: This retrospective analysis revealed that immunotherapy provided limited additional benefit to chemotherapy in TKI-refractory EGFR-mutant LUAD. Chemotherapy alone or combined with bevacizumab remain good choices for patients with actionable EGFR mutations.

Original language	English (US)
Article number	3473
Journal	Cancers
Volume	14
Issue number	14
DOIs	https://doi.org/10.3390/cancers14143473
State	Published - Jul 2022

Keywords

EGFR
chemotherapy
immunotherapy
lung adenocarcinoma
tyrosine kinase inhibitors

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Biostatistics Resource Group

Access to Document

10.3390/cancers14143473

Cite this

Hong, L., Lewis, W. E., Nilsson, M., Patel, S., Varghese, S., Rivera, M. J., Du, R. R., Chen, P., Kemp, H. N., Rinsurongkawong, W., Heeke, S., Spelman, A. R., Elamin, Y. Y., Negrao, M. V., Sepesi, B., Gibbons, D. L., Lee, J. J., Wu, J., Vokes, N. I., ... Le, X. (2022). Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma. Cancers, 14(14), Article 3473. https://doi.org/10.3390/cancers14143473

Hong, L, Lewis, WE, Nilsson, M, Patel, S, Varghese, S, Rivera, MJ, Du, RR, Chen, P, Kemp, HN, Rinsurongkawong, W, Heeke, S, Spelman, AR, Elamin, YY , Negrao, MV, Sepesi, B, Gibbons, DL , Lee, JJ , Wu, J , Vokes, NI , Heymach, JV , Zhang, J & Le, X 2022, 'Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma', Cancers, vol. 14, no. 14, 3473. https://doi.org/10.3390/cancers14143473

@article{0757918d72754a4da519b973e26efec3,

title = "Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma",

abstract = "Background: The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting. Methods: This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; n = 84), chemotherapy combined with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n = 42), and IO monotherapy (IO-mono; n = 22). Clinical progression-free survival (PFS) and overall survival (OS) were evaluated. Associations of clinical characteristics with outcomes were assessed using univariable and multi-covariate Cox Proportional Hazards regression models. Results: A total of 178 patients (median age = 63.3; 57.9% females) with a median follow-up time of 42.0 (Interquartile range: 22.9–67.8) months were enrolled. There was no significant difference in PFS between chemoIO vs. chemo groups (5.3 vs. 4.8 months, p = 0.8). Compared to the chemo group, patients who received withBev therapy trended towards better PFS (6.1 months vs. 4.8; p = 0.3; HR 0.79; 95% CI: 0.52–1.20), while patients treated with IO-mono had inferior PFS (2.2 months; p = 0.001; HR 2.22; 95% CI: 1.37–3.59). Furthermore, PD-L1 level was not associated with PFS benefit in the chemoIO group. Patients with EGFR-mutant LUAD with high PD-L1 (≥50%) had shorter PFS (5.8 months) than non-EGFR/ALK LUAD patients who received chemoIO (12.8 months, p = 0.002; HR 0.22; 95% CI: 0.08–0.56) as first-line treatment. Chemotherapy-based therapy rendered similar benefit to patients with either EGFR exon19 deletion vs. L858R in the LUAD. Conclusions: This retrospective analysis revealed that immunotherapy provided limited additional benefit to chemotherapy in TKI-refractory EGFR-mutant LUAD. Chemotherapy alone or combined with bevacizumab remain good choices for patients with actionable EGFR mutations.",

keywords = "EGFR, chemotherapy, immunotherapy, lung adenocarcinoma, tyrosine kinase inhibitors",

author = "Lingzhi Hong and Lewis, {Whitney E.} and Monique Nilsson and Sonia Patel and Susan Varghese and Rivera, {Melvin J.} and Du, {Robyn R.} and Pingjun Chen and Kemp, {Haley N.} and Waree Rinsurongkawong and Simon Heeke and Spelman, {Amy R.} and Elamin, {Yasir Y.} and Negrao, {Marcelo V.} and Boris Sepesi and Gibbons, {Don L.} and Lee, {J. Jack} and Jia Wu and Vokes, {Natalie I.} and Heymach, {John V.} and Jianjun Zhang and Xiuning Le",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = jul,

doi = "10.3390/cancers14143473",

language = "English (US)",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "14",

}

TY - JOUR

T1 - Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma

AU - Hong, Lingzhi

AU - Lewis, Whitney E.

AU - Nilsson, Monique

AU - Patel, Sonia

AU - Varghese, Susan

AU - Rivera, Melvin J.

AU - Du, Robyn R.

AU - Chen, Pingjun

AU - Kemp, Haley N.

AU - Rinsurongkawong, Waree

AU - Heeke, Simon

AU - Spelman, Amy R.

AU - Elamin, Yasir Y.

AU - Negrao, Marcelo V.

AU - Sepesi, Boris

AU - Gibbons, Don L.

AU - Lee, J. Jack

AU - Wu, Jia

AU - Vokes, Natalie I.

AU - Heymach, John V.

AU - Zhang, Jianjun

AU - Le, Xiuning

PY - 2022/7

Y1 - 2022/7

N2 - Background: The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting. Methods: This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; n = 84), chemotherapy combined with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n = 42), and IO monotherapy (IO-mono; n = 22). Clinical progression-free survival (PFS) and overall survival (OS) were evaluated. Associations of clinical characteristics with outcomes were assessed using univariable and multi-covariate Cox Proportional Hazards regression models. Results: A total of 178 patients (median age = 63.3; 57.9% females) with a median follow-up time of 42.0 (Interquartile range: 22.9–67.8) months were enrolled. There was no significant difference in PFS between chemoIO vs. chemo groups (5.3 vs. 4.8 months, p = 0.8). Compared to the chemo group, patients who received withBev therapy trended towards better PFS (6.1 months vs. 4.8; p = 0.3; HR 0.79; 95% CI: 0.52–1.20), while patients treated with IO-mono had inferior PFS (2.2 months; p = 0.001; HR 2.22; 95% CI: 1.37–3.59). Furthermore, PD-L1 level was not associated with PFS benefit in the chemoIO group. Patients with EGFR-mutant LUAD with high PD-L1 (≥50%) had shorter PFS (5.8 months) than non-EGFR/ALK LUAD patients who received chemoIO (12.8 months, p = 0.002; HR 0.22; 95% CI: 0.08–0.56) as first-line treatment. Chemotherapy-based therapy rendered similar benefit to patients with either EGFR exon19 deletion vs. L858R in the LUAD. Conclusions: This retrospective analysis revealed that immunotherapy provided limited additional benefit to chemotherapy in TKI-refractory EGFR-mutant LUAD. Chemotherapy alone or combined with bevacizumab remain good choices for patients with actionable EGFR mutations.

AB - Background: The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting. Methods: This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; n = 84), chemotherapy combined with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n = 42), and IO monotherapy (IO-mono; n = 22). Clinical progression-free survival (PFS) and overall survival (OS) were evaluated. Associations of clinical characteristics with outcomes were assessed using univariable and multi-covariate Cox Proportional Hazards regression models. Results: A total of 178 patients (median age = 63.3; 57.9% females) with a median follow-up time of 42.0 (Interquartile range: 22.9–67.8) months were enrolled. There was no significant difference in PFS between chemoIO vs. chemo groups (5.3 vs. 4.8 months, p = 0.8). Compared to the chemo group, patients who received withBev therapy trended towards better PFS (6.1 months vs. 4.8; p = 0.3; HR 0.79; 95% CI: 0.52–1.20), while patients treated with IO-mono had inferior PFS (2.2 months; p = 0.001; HR 2.22; 95% CI: 1.37–3.59). Furthermore, PD-L1 level was not associated with PFS benefit in the chemoIO group. Patients with EGFR-mutant LUAD with high PD-L1 (≥50%) had shorter PFS (5.8 months) than non-EGFR/ALK LUAD patients who received chemoIO (12.8 months, p = 0.002; HR 0.22; 95% CI: 0.08–0.56) as first-line treatment. Chemotherapy-based therapy rendered similar benefit to patients with either EGFR exon19 deletion vs. L858R in the LUAD. Conclusions: This retrospective analysis revealed that immunotherapy provided limited additional benefit to chemotherapy in TKI-refractory EGFR-mutant LUAD. Chemotherapy alone or combined with bevacizumab remain good choices for patients with actionable EGFR mutations.

KW - EGFR

KW - chemotherapy

KW - immunotherapy

KW - lung adenocarcinoma

KW - tyrosine kinase inhibitors

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UR - http://www.scopus.com/inward/citedby.url?scp=85137210063&partnerID=8YFLogxK

U2 - 10.3390/cancers14143473

DO - 10.3390/cancers14143473

M3 - Article

C2 - 35884533

AN - SCOPUS:85137210063

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 14

M1 - 3473

ER -

Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma

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MD Anderson CCSG core facilities

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