1Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
2Department of Hematology-Oncology, Chungbuk National University Hospital, Cheongju, Korea
3Biometric Research Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea
Copyright © 2017 by the Korean Cancer Association
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Characteristic | Afatinib+Simvastatin | Afatinib | p-value |
---|---|---|---|
Age, median (range, yr) | 59 (44-80) | 67 (44-78) | 0.008 |
Sex | |||
Male | 32 (88.9) | 27 (84.4) | 0.725 |
Female | 4 (11.1) | 5 (15.6) | |
Smoking | |||
Never | 4 (11.1) | 1 (3.1) | 0.460 |
Ever | 31 (86.1) | 30 (93.8) | |
Unknown | 1 (2.8) | 1 (3.1) | |
Pathology | |||
Squamous cell carcinoma | 33 (91.7) | 31 (96.9) | 0.616 |
Other | 3 (8.3) | 1 (3.1) | |
ECOG PS | |||
0-1 | 27 (75.0) | 24 (75.0) | 0.854 |
2 | 9 (25.0) | 8 (25.0) | |
No. of prior chemotherapies | |||
1 | 21 (58.3) | 19 (59.4) | 1.000 |
2 | 15 (41.7) | 13 (40.6) | |
EGFR mutation | |||
Wild type | 32 (88.8) | 28 (87.6) | 1.000 |
Mutant typea) | 2 (5.6) | 2 (6.2) | |
Unknown | 2 (5.6) | 2 (6.2) | |
EGFR FISH | |||
Negative | 30 (83.4) | 26 (81.3) | 1.000 |
Positive | 3 (8.3) | 2 (6.2) | |
Unknown | 3 (8.3) | 4 (12.5) | |
EGFR IHC | |||
Negative | 14 (38.9) | 10 (31.3) | 0.698 |
Positive | 17 (47.2) | 15 (46.9) | |
Unknown | 5 (13.9) | 7 (21.9) |
EGFR biomarker | No. | Pathology SCC | Smoking never | Response CR+PR | PFS (mo) |
---|---|---|---|---|---|
EGFR wild type | 60 | 56 (93) | 4 (7) | 3 (5) | 1.9 |
EGFR mutation type | 4 | 4 (100) | 0 | 2 (50) | 2.9 |
Exon 19 deletion | 1 | SCC | Ex-smoker | CR | 23.2 |
Exon 20 G810S | 1 | SCC | Ex-smoker | PR | 2.9 |
Exon 20 V786M | 1 | SCC | Ex-smoker | PD | 1.0 |
Exon 21 G863S | 1 | SCC | Ex-smoker | SD | 5.2 |
EGFR/FISH negativity | 56 | 54 (96) | 3 (5) | 3 (5) | 1.9 |
EGFR/FISH positivity | 5 | 4 (80) | 1 (20) | 2 (40) | 3.6 |
High polysomy | 1 | SCC | Current smoker | PR | 5.4 |
High polysomy | 1 | SCC | Ex-smoker | SD | 4.0 |
Gene amplification | 1 | NSCLC-NOS | Never smoker | PR | 3.6 |
Botha) | 1 | SCC | Current smoker | PD | 1.0 |
Botha) | 1 | SCC | Ex-smoker | PD | 0.9 |
EGFR/IHC negativity | 24 | 21 (88) | 4 (17) | 1 (4) | 3.6 |
EGFR/IHC positivity | 32 | 32 (100) | 1 (3) | 4 (12.5) | 1.9 |
2+ | 16 | 16 (100) | 0 | 1 (6) | 1.0 |
3+ | 16 | 16 (100) | 1 (6) | 3 (19) | 1.9 |
Variable |
Univariate |
Multivariate |
||
---|---|---|---|---|
HR (95% CI) | p-valuea) | HR (95% CI) | p-valuea) | |
Age (≤ 65 yr vs. > 65 yr) | 1.03 (0.61-1.70) | 0.926 | ||
Sex (female vs. male) | 0.77 (0.38-1.57) | 0.470 | ||
ECOG PS (0, 1 vs. 2) | 0.60 (0.34-1.05) | 0.072 | 0.64 (0.36-1.16) | 0.140 |
Never vs. ever smoker | 1.81 (0.71-4.60) | 0.212 | ||
Previous chemotherapy (1 vs. 2) | 0.98 (0.59-1.63) | 0.945 | ||
EGFR (mutated vs. wild type) | 0.42 (0.13-1.36) | 0.147 | ||
EGFR/FISH+ vs. FISH– | 1.03 (0.41-2.61) | 0.946 | ||
EGFR IHC+ vs. IHC– | 0.99 (0.56-1.75) | 0.977 | ||
Skin rash grade (≥ 2 vs. < 2) | 0.44 (0.25-0.78) | 0.005 | 0.55 (0.30-0.99) | 0.049 |
Stomatitis grade (≥ 2 vs. < 2) | 0.65 (0.39-1.10) | 0.107 | ||
Diarrhea grade (≥ 2 vs. < 2) | 0.98 (0.59-1.63) | 0.946 |
Characteristic | Afatinib+Simvastatin | Afatinib | p-value |
---|---|---|---|
Age, median (range, yr) | 59 (44-80) | 67 (44-78) | 0.008 |
Sex | |||
Male | 32 (88.9) | 27 (84.4) | 0.725 |
Female | 4 (11.1) | 5 (15.6) | |
Smoking | |||
Never | 4 (11.1) | 1 (3.1) | 0.460 |
Ever | 31 (86.1) | 30 (93.8) | |
Unknown | 1 (2.8) | 1 (3.1) | |
Pathology | |||
Squamous cell carcinoma | 33 (91.7) | 31 (96.9) | 0.616 |
Other | 3 (8.3) | 1 (3.1) | |
ECOG PS | |||
0-1 | 27 (75.0) | 24 (75.0) | 0.854 |
2 | 9 (25.0) | 8 (25.0) | |
No. of prior chemotherapies | |||
1 | 21 (58.3) | 19 (59.4) | 1.000 |
2 | 15 (41.7) | 13 (40.6) | |
EGFR mutation | |||
Wild type | 32 (88.8) | 28 (87.6) | 1.000 |
Mutant type |
2 (5.6) | 2 (6.2) | |
Unknown | 2 (5.6) | 2 (6.2) | |
EGFR FISH | |||
Negative | 30 (83.4) | 26 (81.3) | 1.000 |
Positive | 3 (8.3) | 2 (6.2) | |
Unknown | 3 (8.3) | 4 (12.5) | |
EGFR IHC | |||
Negative | 14 (38.9) | 10 (31.3) | 0.698 |
Positive | 17 (47.2) | 15 (46.9) | |
Unknown | 5 (13.9) | 7 (21.9) |
Response | Afatinib+Simvastatin | Afatinib | p-value |
---|---|---|---|
Complete response | 0 | 1 | |
Partial response | 2 | 2 | |
Stable disease | 14 | 21 | |
Disease progression | 19 | 8 | |
Not evaluable | 1 | 0 | |
Overall response rate (complete response+partial response) (%) | 5.7 | 9.4 | 0.430 |
Adverse effect | Afatinib+Simvastatin |
Afatinib |
||
---|---|---|---|---|
≥ Grade 3 | Total grade | ≥ Grade 3 | Total grade | |
AST/ALT increased | 1 (2.8) | 4 (11.1) | 0 | 1 (3.1) |
Creatinine increased | 0 | 4 (11.1) | 1 (3.1) | 7 (21.9) |
QT prolonged | 0 | 6 (16.7) | 1 (3.1) | 4 (12.5) |
Fatigue | 0 | 10 (27.8) | 1 (3.1) | 11 (34.4) |
Anorexia | 1 (2.8) | 11 (30.6) | 0 | 14 (43.8) |
Weight loss | 0 | 2 (5.6) | 0 | 6 (18.8) |
Diarrhea | 2 (5.6) | 23 (63.9) | 6 (18.8) | 27 (84.4) |
Stomatitis | 0 | 24 (66.7) | 2 (6.3) | 25 (78.1) |
Dry skin | 0 | 7 (19.4) | 0 | 6 (18.8) |
Pruritus | 0 | 15 (41.7) | 0 | 11 (34.4) |
Skin rash | 1 (2.8) | 28 (77.8) | 1 (3.1) | 25 (78.1) |
Paronychia | 0 | 4 (11.1) | 0 | 4 (12.5) |
Hand-foot syndrome | 0 | 5 (13.9) | 0 | 5 (15.6) |
Esophageal ulcer | 1 (2.8) | 1 (2.8) | 0 | 0 |
Idiopathic bilateral vocal cord palsy | 0 | 0 | 1 (3.1) | 1 (3.1) |
EGFR biomarker | No. | Pathology SCC | Smoking never | Response CR+PR | PFS (mo) |
---|---|---|---|---|---|
EGFR wild type | 60 | 56 (93) | 4 (7) | 3 (5) | 1.9 |
EGFR mutation type | 4 | 4 (100) | 0 | 2 (50) | 2.9 |
Exon 19 deletion | 1 | SCC | Ex-smoker | CR | 23.2 |
Exon 20 G810S | 1 | SCC | Ex-smoker | PR | 2.9 |
Exon 20 V786M | 1 | SCC | Ex-smoker | PD | 1.0 |
Exon 21 G863S | 1 | SCC | Ex-smoker | SD | 5.2 |
EGFR/FISH negativity | 56 | 54 (96) | 3 (5) | 3 (5) | 1.9 |
EGFR/FISH positivity | 5 | 4 (80) | 1 (20) | 2 (40) | 3.6 |
High polysomy | 1 | SCC | Current smoker | PR | 5.4 |
High polysomy | 1 | SCC | Ex-smoker | SD | 4.0 |
Gene amplification | 1 | NSCLC-NOS | Never smoker | PR | 3.6 |
Both |
1 | SCC | Current smoker | PD | 1.0 |
Both |
1 | SCC | Ex-smoker | PD | 0.9 |
EGFR/IHC negativity | 24 | 21 (88) | 4 (17) | 1 (4) | 3.6 |
EGFR/IHC positivity | 32 | 32 (100) | 1 (3) | 4 (12.5) | 1.9 |
2+ | 16 | 16 (100) | 0 | 1 (6) | 1.0 |
3+ | 16 | 16 (100) | 1 (6) | 3 (19) | 1.9 |
Variable | Univariate |
Multivariate |
||
---|---|---|---|---|
HR (95% CI) | p-value |
HR (95% CI) | p-value |
|
Age (≤ 65 yr vs. > 65 yr) | 1.03 (0.61-1.70) | 0.926 | ||
Sex (female vs. male) | 0.77 (0.38-1.57) | 0.470 | ||
ECOG PS (0, 1 vs. 2) | 0.60 (0.34-1.05) | 0.072 | 0.64 (0.36-1.16) | 0.140 |
Never vs. ever smoker | 1.81 (0.71-4.60) | 0.212 | ||
Previous chemotherapy (1 vs. 2) | 0.98 (0.59-1.63) | 0.945 | ||
EGFR (mutated vs. wild type) | 0.42 (0.13-1.36) | 0.147 | ||
EGFR/FISH+ vs. FISH– | 1.03 (0.41-2.61) | 0.946 | ||
EGFR IHC+ vs. IHC– | 0.99 (0.56-1.75) | 0.977 | ||
Skin rash grade (≥ 2 vs. < 2) | 0.44 (0.25-0.78) | 0.005 | 0.55 (0.30-0.99) | 0.049 |
Stomatitis grade (≥ 2 vs. < 2) | 0.65 (0.39-1.10) | 0.107 | ||
Diarrhea grade (≥ 2 vs. < 2) | 0.98 (0.59-1.63) | 0.946 |
ECOG, Eastern Cooperative Oncology Group; PS, performance status; EGFR, epidermal growth factor receptor; FISH, fluorescence Uncommon
AST, aspartate aminotransferase; ALT, alanine transaminase.
Values are presented as number (%). EGFR, epidermal growth factor receptor; SCC, squamous cell carcinoma; CR, complete response; PR, partial response; PFS, progression-free survival; FISH, fluorescence Highpolysomy and gene amplification.
HR, hazard ratio; CI, confidential interval; ECOG, Eastern Cooperative Group; PS, performance status; FISH, fluorescence Tested with the Cox proportional hazards model.