The impact of TP53 co-mutations and immunologic microenvironment on outcome of lung cancer with EGFR exon 20 insertions

被引：23

作者：

Christopoulos, Petros ^{[1
,2
,25
,26
,27
]}

Kluck, Klaus ^{[3
]}

Kirchner, Martina ^{[3
]}

Lueders, Heike ^{[4
]}

Roeper, Julia ^{[5
]}

Falkenstern-Ge, Roger-Fei ^{[6
]}

Szewczyk, Marlen

Sticht, Florian ^{[7
]}

Saalfeld, Felix C. ^{[8
]}

Wesseler, Claas ^{[9
]}

Hackanson, Bjoern ^{[10
,11
]}

Dintner, Sebastian ^{[12
]}

Faehling, Martin ^{[13
]}

Kuon, Jonas ^{[1
,2
,14
,27
]}

Janning, Melanie ^{[15
,16
]}

Kauffmann-Guerrero, Diego

Kazdal, Daniel ^{[27
]}

Kurz, Sylke ^{[4
]}

Eichhorn, Florian ^{[18
,19
,27
]}

Bozorgmehr, Farastuk ^{[1
,2
,27
]}

Shah, Rajiv ^{[1
,2
,27
]}

Tufman, Amanda ^{[17
,27
]}

Wermke, Martin ^{[8
]}

Loges, Sonja ^{[15
,16
]}

Brueckl, Wolfgang M.

Schulz, Christian ^{[4
,7
]}

Misch, Daniel ^{[21
]}

Frost, Nikolaj ^{[22
]}

Kollmeier, Jens ^{[20
]}

Reck, Martin ^{[23
,27
]}

Griesinger, Frank ^{[5
]}

Grohe, Christian

Hong, Jin-Liern ^{[24
,25
,26
]}

Lin, Huamao M. ^{[24
,26
]}

Budczies, Jan ^{[3
,27
]}

Stenzinger, Albrecht ^{[3
,27
]}

Thomas, Michael ^{[1
,2
,27
]}

机构：

[1] Heidelberg Univ Hosp, Dept Thorac Oncol, Thoraxklin, Rontgenstr 1, D-69126 Heidelberg, Germany

[2] Heidelberg Univ Hosp, Natl Ctr Tumor Dis, Rontgenstr 1, D-69126 Heidelberg, Germany

[3] Heidelberg Univ Hosp, Inst Pathol, Heidelberg, Germany

[4] Protestant Lung Hosp, Dept Pneumol, Berlin, Germany

[5] Carl von Ossietzky Univ Oldenburg, Dept Hematol & Oncol, Pius Hosp, Dept Internal Med Oncol, Oldenburg, Germany

[6] Robert Bosch Ctr Tumor Dis RBCT, Dept Thorac Oncol, D-70376 Stuttgart, Germany

[7] Univ Hosp Regensburg, Clin & Polyclin Internal Med 2, D-93042 Regensburg, Germany

[8] Tech Univ Dresden, Univ Hosp, Clin Internal Med 1, Dresden, Germany

[9] Asklepios Klinikum Harburg, Dept Thorac Oncol, Harburg, Germany

[10] Univ Med Ctr Augsburg, Dept Hematol Oncol, Augsburg, Germany

[11] Univ Freiburg, Freiburg Univ Hosp, Fac Med, Dept Med 1, Freiburg, Germany

[12] Univ Augsburg, Fac Med, Gen Pathol & Mol Diagnost, Augsburg, Germany

[13] Esslingen Hosp, Dept Pneumol, Esslingen, Germany

[14] Lungenklin Loewenstein, Dept Thorac Oncol, Loewenstein, Germany

[15] German Canc Res Ctr, Div Personalized Med Oncol, Heidelberg, Germany

[16] Heidelberg Univ, Med Fac Mannheim, Univ Hosp Mannheim, Dept Personalized Oncol, Mannheim, Germany

[17] Hosp LMU Munich, Med Clin 5, Dept Pneumol, D-80336 Munich, Germany

[18] Heidelberg Univ Hosp, Thorac Surg, Thoraxklinik, Heidelberg, Germany

[19] Heidelberg Univ Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany

[20] Paracelsus Med Univ, Nurnberg, Germany

[21] Nuernberg Gen Hosp, Dept Resp Med, Allergol & Sleep Med Nuernberg Lung Canc Ctr, Nurnberg, Germany

[22] Helios Klinikum Emil Behring, Dept Pneumol, Berlin, Germany

[23] Charite, Dept Pneumol, Berlin, Germany

[24] Lungenclin Grosshansdorf, Dept Pneumol, Grosshansdorf, Germany

[25] Millennium Pharmaceut Inc, Cambridge, MA USA

[26] Takeda Pharmaceut Co Ltd, Cambridge, MA USA

[27] German Ctr Lung Res DZL, Berlin, Germany

来源：

EUROPEAN JOURNAL OF CANCER | 2022年 / 170卷

关键词：

EGFR(+) NSCLC; EGFR exon 20; TP53; mutation; Brain metastases; Immunologic tumour microenvironment; CD8; cells; Th1; Treatment failure; Overall survival; PRETREATED PATIENTS; MOBOCERTINIB; NSCLC; SURVIVAL; DIAGNOSIS;

D O I：

10.1016/j.ejca.2022.04.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: EGFR exon20 insertions (ex20ins) are targeted by novel compounds in non-small-cell lung cancer (NSCLC). However, data about outcome under conventional therapies and the influence of molecular features are scarce. Patients and methods: We retrospectively analysed 118 patients with evaluation of radiologic response based on RECIST v1.1. TP53 status was available for 88 cases. Results: Platinum doublets and chemoimmunotherapy showed similar response rates (20-25%), disease control rates (80%) and median progression-free survival (mPFS, asymptotic to 7 months), which were longer compared to monochemotherapy (9%, 59%, 4.1 months), EGFR inhibitors (0%, 46%, 3.0) and PD-(L)1 inhibitors (0%, 30%, 2.1; p < 0.05). Overall survival (OS) was not dependent on the choice of first-line treatment, but related to more lines of systemic therapy (p < 0.05). TP53 mutations and brain metastases were associated with shorter PFS under platinum doublets and EGFR inhibitors (HR 3.3-6.1, p < 0.01), and shorter OS for patients receiving both treatments (p < 0.05). More tumour CD8(+) and less Th1 cells were associated with longer OS independent of brain and TP53 status (p < 0.01). No difference in outcome was noted according to the ex20ins site and use of pemetrexed (vs. other cytotoxics) or bevacizumab. Long-lasting responses (>1 year) occasionally occurred under EGFR inhibitors for both 'near-' and 'far-loop' variants. Conclusions: Platinum doublets and chemoimmunotherapy have the highest activity with ORR of 20-25% and mPFS of approximately 7 months, regardless of the cytotoxic partner, while PD-(L)1 inhibitors show limited efficacy. TP53 mutations, brain metastases and a lower tumour CD8/Th1-cell ratio are independently associated with shorter survival. (C) 2022 Elsevier Ltd. All rights reserved.

引用

页码：106 / 118

页数：13

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