1Center for Clinical Trials, National Cancer Center, Goyang, Korea
2Department of Pathology, National Cancer Center, Goyang, Korea
3Center for Lung Cancer, National Cancer Center, Goyang, Korea
4Department of Radiology, National Cancer Center, Goyang, Korea
Copyright © 2021 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
This study was approved by the Institutional Review Board (IRB) of the National Cancer Center (IRB number; NCC2019-0074). All patients provided written consent for participating in the screening for the phase 2 trial of capmatinib (NCT02414139) and providing their data for GEOMETRY study.
Author Contributions
Conceived and designed the analysis: Choi W, Han JY.
Collected the data: Choi W, Park SY, Lee Y, Lim KY, Lee GK, Han JY.
Contributed data or analysis tools: Park SY, Lee Y, Lim KY, Park M, Han JY.
Performed the analysis: Choi W, Han JY.
Wrote the paper: Choi W, Han JY.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Total | Group A (GCN ≥ 10 or METex14) | Group B (others) | |
---|---|---|---|
GCN | 72 | 14 | 58 |
Mean (range) | 5.9 (1.8–22.8) | 11.9 (4.1–22.8) | 4.5 (1.8–8.5) |
GCN ≥ 10 | 10 (13.9) | 10 (71.4) | 0 |
GCN < 10 | 62 (86.1) | 4 (28.6) | 58 (100) |
Exon 14 skipping mutation | 64 | 12 | 52 |
Present | 5 (7.8) | 5 (41.7) | 0 |
Absent | 59 (92.2) | 7 (58.3) | 52 (100) |
Immunohistochemistrya) | 66 | 13 | 53 |
High | 32 (48.5) | 8 (61.5) | 24 (45.3) |
Intermediate | 17 (25.8) | 1 (7.7) | 16 (30.2) |
Low | 17 (25.8) | 4 (30.8) | 13 (24.5) |
Total (n=14) | Capmatinib (−) (n=6, 42.9%) | Capmatinib (+) (n=8, 57.1%) | p-value | |
---|---|---|---|---|
Age (yr) | 69.5 (57–79) | 68.0 (57–74) | 70.0 (57–79) | 0.559 |
Sex | ||||
Male | 14 (100) | 6 (100) | 8 (100) | > 0.99 |
Female | 0 | 0 | 0 | |
Histology | ||||
Adenocarcinoma | 13 (92.9) | 6 (100) | 7 (87.5) | > 0.99 |
Squamous cell carcinoma | 1 (7.1) | 0 | 1 (12.5) | |
Other | 0 | 0 | 0 | |
Smoking history | ||||
Current or former | 12 (85.7) | 5 (83.3) | 7 (87.5) | > 0.99 |
Never | 2 (14.3) | 1 (16.7) | 1 (12.5) | |
Stage | ||||
III | 3 (21.4) | 1 (16.7) | 2 (25.0) | > 0.99 |
IV | 11 (78.6) | 5 (83.3) | 6 (75.0) | |
ECOG PS | ||||
0 | 4 (28.6) | 2 (33.3) | 2 (25.0) | > 0.99 |
1 | 10 (71.4) | 4 (66.7) | 6 (75.0) | |
First-line treatment | ||||
Platinum-doubleta) | 13 (92.9) | 6 (100) | 7 (87.5) | |
Capmatinib | 1 (7.1) | 0 | 1 (12.5) | |
Second-line treatment | ||||
Platinum-doubleta) | 3 (21.4) | 2 (33.3) | 1 (12.5) | |
Pemetrexed | 1 (7.1) | 1 (16.7) | 0 | |
Capmatinib | 7 (50.0) | 0 | 7 (87.5) |
Clinical characteristics of patients
Total (n=72) | Group A (GCN ≥ 10 or METex14) (n=14, 19.4%) | Group B (others) (n=58, 80.6%) | p-value | |
---|---|---|---|---|
Age, mean (range, yr) | 62.2 (32–79) | 67.7 (57–79) | 60.8 (32–79) | 0.014 |
Sex | ||||
Male | 60 (83.3) | 14 (100) | 46 (79.3) | 0.106 |
Female | 12 (16.7) | 0 | 12 (20.7) | |
Histology | ||||
Adenocarcinoma | 58 (80.6) | 13 (92.9) | 45 (77.6) | 0.663 |
Squamous cell carcinoma | 10 (13.9) | 1 (7.1) | 9 (15.5) | |
Other | 4 (5.5) | 0 | 4 (6.9) | |
Smoking history | ||||
Never | 8 (11.1) | 2 (14.3) | 6 (10.3) | |
Current or former | 64 (88.9) | 12 (85.7) | 52 (89.7) | 0.648 |
Pack years | 36.2 (0.1–120.0) | 30.2 (1.0–94.0) | 37.5 (0.1–120.0) | 0.380 |
Stage | ||||
III | 7 (9.7) | 3 (21.4) | 4 (6.9) | 0.128 |
IV | 65 (90.3) | 11 (78.6) | 54 (93.1) | |
ECOG PS | ||||
0 | 24 (33.3) | 4 (28.6) | 20 (34.5) | 0.762 |
1 | 48 (66.7) | 10 (71.4) | 38 (65.5) |
Values are presented as mean (range) or number (%). ECOG PS, Eastern Cooperative Oncology Group performance status; GCN, gene copy number; METex14, MET exon 14 skipping mutation.
Assessments of the MET status
Total | Group A (GCN ≥ 10 or METex14) | Group B (others) | |
---|---|---|---|
GCN | 72 | 14 | 58 |
Mean (range) | 5.9 (1.8–22.8) | 11.9 (4.1–22.8) | 4.5 (1.8–8.5) |
GCN ≥ 10 | 10 (13.9) | 10 (71.4) | 0 |
GCN < 10 | 62 (86.1) | 4 (28.6) | 58 (100) |
Exon 14 skipping mutation | 64 | 12 | 52 |
Present | 5 (7.8) | 5 (41.7) | 0 |
Absent | 59 (92.2) | 7 (58.3) | 52 (100) |
Immunohistochemistry |
66 | 13 | 53 |
High | 32 (48.5) | 8 (61.5) | 24 (45.3) |
Intermediate | 17 (25.8) | 1 (7.7) | 16 (30.2) |
Low | 17 (25.8) | 4 (30.8) | 13 (24.5) |
Values are presented as number (%) unless otherwise indicated. GCN, gene copy number; METex14, MET exon 14 skipping mutation.
a)High: intensity 3+ and proportion > 50%; Intermediate: intensity 2+ and proportion > 50%, or intensity 3+ and proportion 25%–50%; Low: intensity 1+ or proportion < 25%.
Best overall response to capmatinib
Total (n=13) | Group A (GCN ≥ 10 or METex14) (n=8, 61.5%) | Group B (others) (n=5, 38.5%) | |
---|---|---|---|
Best response, n (%) | |||
Complete remission | 0 | 0 | 0 |
Partial response | 4 (30.8) | 4 (50.0) | 0 |
Stable disease | 2 (15.4) | 1 (12.5) | 1 (20.0) |
Progressive disease | 7 (53.8) | 3 (37.5) | 4 (80.0) |
Overall response rate (%) | 30.8 | 50.0 | 0 |
GCN, gene copy number; METex14, MET exon 14 skipping mutation.
Clinical characteristics of patients with c-MET GCN ≥ 10 or METex14
Total (n=14) | Capmatinib (−) (n=6, 42.9%) | Capmatinib (+) (n=8, 57.1%) | p-value | |
---|---|---|---|---|
Age (yr) | 69.5 (57–79) | 68.0 (57–74) | 70.0 (57–79) | 0.559 |
Sex | ||||
Male | 14 (100) | 6 (100) | 8 (100) | > 0.99 |
Female | 0 | 0 | 0 | |
Histology | ||||
Adenocarcinoma | 13 (92.9) | 6 (100) | 7 (87.5) | > 0.99 |
Squamous cell carcinoma | 1 (7.1) | 0 | 1 (12.5) | |
Other | 0 | 0 | 0 | |
Smoking history | ||||
Current or former | 12 (85.7) | 5 (83.3) | 7 (87.5) | > 0.99 |
Never | 2 (14.3) | 1 (16.7) | 1 (12.5) | |
Stage | ||||
III | 3 (21.4) | 1 (16.7) | 2 (25.0) | > 0.99 |
IV | 11 (78.6) | 5 (83.3) | 6 (75.0) | |
ECOG PS | ||||
0 | 4 (28.6) | 2 (33.3) | 2 (25.0) | > 0.99 |
1 | 10 (71.4) | 4 (66.7) | 6 (75.0) | |
First-line treatment | ||||
Platinum-doublet |
13 (92.9) | 6 (100) | 7 (87.5) | |
Capmatinib | 1 (7.1) | 0 | 1 (12.5) | |
Second-line treatment | ||||
Platinum-doublet |
3 (21.4) | 2 (33.3) | 1 (12.5) | |
Pemetrexed | 1 (7.1) | 1 (16.7) | 0 | |
Capmatinib | 7 (50.0) | 0 | 7 (87.5) |
Values are presented as median (range) or number (%). ECOG PS, Eastern Cooperative Oncology Group performance status; GCN, gene copy number; METex14, MET exon 14 skipping mutation.
a)Platinum-doublet regimens include pemetrexed+platinum, gemcitabine+platinum, or taxane+platinum.
Values are presented as mean (range) or number (%). ECOG PS, Eastern Cooperative Oncology Group performance status; GCN, gene copy number;
Values are presented as number (%) unless otherwise indicated. GCN, gene copy number; High: intensity 3+ and proportion > 50%; Intermediate: intensity 2+ and proportion > 50%, or intensity 3+ and proportion 25%–50%; Low: intensity 1+ or proportion < 25%.
GCN, gene copy number;
Values are presented as median (range) or number (%). ECOG PS, Eastern Cooperative Oncology Group performance status; GCN, gene copy number; Platinum-doublet regimens include pemetrexed+platinum, gemcitabine+platinum, or taxane+platinum.