First-line immunotherapy for lung cancer with MET exon 14 skipping and the relevance of TP53 mutations

被引：12

作者：

Blasi, Miriam ^{[1
,2
,3
,4
]}

Kuon, Jonas ^{[1
,2
,3
,4
,5
]}

Lueders, Heike ^{[6
]}

Misch, Daniel ^{[7
]}

Kauffmann-Guerrero, Diego ^{[8
,22
,23
]}

Hilbrandt, Moritz ^{[9
,10
,11
,12
]}

Kazdal, Daniel ^{[3
,4
,13
]}

Falkenstern-Ge, Roger-Fei ^{[14
]}

Hackanson, Bjoern ^{[15
,16
]}

Dintner, Sebastian ^{[17
]}

Faehling, Martin ^{[18
]}

Kirchner, Martina ^{[13
]}

Volckmar, Anna -Lena ^{[13
]}

Kopp, Hans -Georg ^{[14
]}

Allgaeuer, Michael ^{[4
]}

Grohe, Christian ^{[6
,7
]}

Tufman, Amanda ^{[8
,22
,23
]}

Reck, Martin ^{[19
,20
,21
]}

Frost, Nikolaj ^{[9
,10
,11
,12
]}

Stenzinger, Albrecht ^{[3
,4
,9
,10
,11
,12
,13
]}

Thomas, Michael ^{[1
,2
,3
]}

Christopoulos, Petros ^{[1
,2
,3
,4
,24
]}

机构：

[1] Heidelberg Univ Hosp, Dept Thorac Oncol, Thoraxklin, Heidelberg, Germany

[2] NCT Heidelberg, Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[3] Translat Lung Res Ctr Heidelberg TLRC, Heidelberg, Germany

[4] German Ctr Lung Res DZL, Heidelberg, Germany

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

[6] Evangel Lungenklin Berlin, Dept Resp Med, Berlin, Germany

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

[8] Univ Hosp, Dept Medicine5, Dept Med 5, Munich, Germany

[9] Charite Univ Med Berlin, Dept Infect Dis & Resp Med, Berlin, Germany

[10] Free Univ Berlin, Berlin, Germany

[11] Humboldt Univ, Berlin, Germany

[12] Berlin Inst Hlth, Berlin, Germany

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

[14] Robert Bosch Ctr Tumorerkrankungen RBCT, Stuttgart, Germany

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

[16] Univ Freiburg, Fac Med, Med Ctr, Dept Med 1, Freiburg, Germany

[17] Univ Augsburg, Med Fac, Pathol, Augsburg, Germany

[18] Klinikum Esslingen, Klin Kardiol Angiol & Pneumol, Esslingen, Germany

[19] LungenClinic Grosshansdorf, LungenClin Grosshansdorf, Grosshansdorf, Germany

[20] Airway Res Ctr North ARCN, Grosshansdorf, Germany

[21] German Ctr Lung Res DZL, Grosshansdorf, Germany

[22] Comprehens Pneumol Ctr Munich CPC M, Munich, Germany

[23] German Ctr Lung Res DZL, Munich, Germany

[24] Heidelberg Univ Hosp, Rontgenstr, D-69126 Heidelberg, Germany

来源：

EUROPEAN JOURNAL OF CANCER | 2024年 / 199卷

关键词：

Lung cancer; Met exon 14 skipping; Immunotherapy; Tyrosine kinase inhibitors; TP53; PD-L1; EXPRESSION; SURVIVAL; TP53;

D O I：

10.1016/j.ejca.2024.113556

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The efficacy of checkpoint inhibitors for non-small cell lung cancer (NSCLC) with MET exon 14 skipping (MET Delta 14ex) remains controversial. Materials and methods: 110 consecutive MET Delta 14ex NSCLC patients receiving first-line chemotherapy (CHT) and/ or immunotherapy (IO) in 10 German centers between 2016-2022 were analyzed. Results: Combined CHT-IO was given to 35/110 (32%) patients, IO alone to 43/110 (39%), and CHT to 32/110 (29%) upfront. Compared to CHT, CHT-IO showed longer progression-free survival (median PFS 6 vs. 2.5 months, p = 0.004), more objective responses (ORR 49% vs. 28%, p = 0.086) and numerically longer overall survival (OS 16 vs. 10 months, p = 0.240). For IO monotherapy, OS (14 vs. 16 months) and duration of response (26 vs. 22 months) were comparable to those of CHT-IO. Primary progressive disease (PD) was more frequent with IO compared to CHT-IO (13/43 vs. 3/35, p = 0.018), particularly for never-smokers (p = 0.041). Higher PDL1 TPS were not associated with better IO outcomes, but TP53 mutated tumors showed numerically improved ORR (56% vs. 32%, p = 0.088) and PFS (6 vs. 3 months, p = 0.160), as well as longer OS in multivariable analysis (HR=0.54, p = 0.034) compared to their wild-type counterparts. Any second-line treatment was administered to 35/75 (47%) patients, with longer survival for capmatinib or tepotinib compared to crizotinib (PFS 10 vs. 3 months, p = 0.013; OS 16 vs. 13 months, p = 0.270). Conclusion: CHT-IO is superior to CHT, and IO alone also effective for META14ex NSCLC, especially in the presence of TP53 mutations and independent of PD -L1 expression, but never -smokers are at higher risk of primary PD.

引用

页数：8

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