Background
Methods
Study design and patients
Procedure
Statistical analysis
Results
Demographic and clinical characteristics
Demographic and clinical characteristic | No. of patients (n = 85) |
---|---|
Age, year | |
Mean (+ SD) | 59.1 + 10.8 |
Gender, No. (%) | |
Female | 47 (55.3) |
Male | 38 (44.7) |
Ethnicity, No. (%) | |
Chinese | 63 (74.1) |
Non-Chinese (Malay and Indian) | 22 (25.9) |
Smoking history, No. (%) | |
Never smoker | 67 (78.8) |
Previous or current smoker | 18 (21.2) |
ECOG performance status at diagnosis, No. (%) | |
ECOG 0–1 | 69 (81.2) |
ECOG 2–4 | 16 (18.8) |
Tumor histology, No. (%) | |
Adenocarcinoma | 82 (96.5) |
Squamous cell carcinoma | 3 (3.5) |
Tumor stage, No. (%) | |
IIIB | 4 (4.7) |
IV | 81 (95.3) |
Symptomatic baseline brain metastases, No. (%) | |
No | 60 (70.6) |
Yes | 25 (29.4) |
-Parenchymal metastases | 16 (64.0) |
-Leptomeningeal metastases | 7 (28.0) |
-Both parenchymal and leptomeningeal metastases | 2 (8.0) |
Abnormal organ function, No. (%) | |
No | 70 (82.4) |
Yes | 15 (17.6) |
-Blood | 5 (33.3) |
-Renal | 9 (60.0) |
-Liver | 2 (13.3) |
EGFR mutation subtype, No. (%) | |
Exon 19 deletion | 68 (80.0) |
Exon 21 L858R point mutation | 11 (12.9) |
Rare or complex mutations | 6 (7.1) |
-Exon 18 G719X | 2 (33.1) |
-Exon 18 G719X and exon 20 S768I | 1 (16.7) |
-Exon 18 G719X and exon 20 T790 M | 1 (16.7) |
-Exon 19 deletion and exon 20 insertion | 1 (16.7) |
-Exon 20 insertion | 1 (16.7) |
Afatinib starting dose, dose adjustment and optimal dose and treatment of baseline brain metastases
Treatment Pattern and Outcome | Total number of patients (n = 85) |
---|---|
Afatinib starting dose, No. (%) | |
40 mg once daily | 45 (52.9) |
30 mg once daily | 30 (35.3) |
25 mg once daily | 3 (3.5) |
20 mg once daily | 7 (8.2) |
Afatinib dose adjustment, No. (%) | |
Starting dose maintained | 49 (57.6) |
Dose increased | 10 (11.8) |
Dose reduced | 26 (30.6) |
Afatinib optimum dose, No. (%) | |
50 mg once daily | 4 (4.7) |
40 mg once daily | 30 (35.3) |
30 mg once daily | 30 (35.3) |
25 mg once daily | 12 (14.1) |
20 mg once daily | 9 (10.6) |
Brain metastasis treatment, No. (%) | |
No brain metastases | 60 (70.6) |
Afatinib alone | 4 (4.7) |
Afatinib with surgery or radiotherapy | 21 (24.7) |
Treatment outcome
Response to afatinib
Treatment outcome | Total number of patients (n = 85) |
---|---|
Best tumor response, No. (%) | |
Complete response | 2 (2.4) |
Partial response | 63 (74.1) |
Stable disease | 16 (18.8) |
Progressive disease | 4 (4.7) |
Disease progression site, No. (%) | |
None | 29 (34.1) |
New brain lesions | 7 (8.2) |
New lesions at other sites | 49 (57.6) |
Investigation for resistance mechanism, No. (%) | |
No progression | 29 (34.1) |
Not investigated | 25 (29.4) |
Investigated | 31 (36.5) |
-Exon 20 T790 M mutation detected | 13 (42.0) |
-Exon 20 T790 M mutation not detected and no histologic transformation | 18 (58.0) |
Characteristics | ORR, No. (%) | *p-value | gOR (95% CI), p-value | DCR, No. (%) | *p-value | gOR (95% CI), p-value |
---|---|---|---|---|---|---|
EGFR mutation subtype, No. (%) | ||||||
Exon 19 deletion | 52 (76.5) | 0.265 | 2.27 (0.47–11.01), 0.309a | 64 (94.1) | 0.263 | 2.72 (0.41–18.24), 0.302a |
Exon 21 L858R point mutation | 6 (54.5) | 0.40 (0.03–5.21), 0.485b | 9 (81.8) | 2.28 (0.31–16.62), 0.420b | ||
Rare and complex mutation | 5 (83.3) | 6 (100) | ||||
Baseline symptomatic brain metastases, No. (%) | ||||||
No | 49 (81.7) | 0.014 | 4.51 (1.45–14.00), 0.009# | 57 (95.0) | 0.251 | 3.0 (0.55–16.38), 0.205# |
Yes | 14 (56.0) | 22 (88.0) | ||||
ECOG performance status, No. (%) | ||||||
0–1 | 49 (71.0) | 0.175 | 0.27 (0.05–1.44), 0.125# | 64 (92.8) | 0.889 | 0.79 (0.08–8.76), 0.835# |
2–4 | 14 (87.5) | 15 (93.8) | ||||
Abnormal organ function, No. (%) | ||||||
No | 53 (75.7) | 0.468 | 1.27 (0.28–5.81), 0.755# | 64 (91.4) | 0.585 | 0.57 (0.07–4.97), 0.616 # |
Yes | 10 (66.7) | 15 (100) | ||||
Afatinib dose adjustment, No. (%) | ||||||
Dose reduced | 23 (88.5) | 0.084 | 5.53 (1.32–23.24), 0.019c | 25 (96.2) | 0.729 | 3.22 (0.29–35.40), 0.339c |
Dose increased | 8 (80.0) | 2.13 (0.36–12.57), 0.404d | 9 (90.0) | 1.30 (0.11–15.02), 0.835d | ||
Starting dose maintained | 32 (65.3) | 45 (91.8) | ||||
Optimal afatinib dose, No. (%) | ||||||
Less than 40 mg once daily | 40 (78.4) | 0.156 | 2.03 (0.59–6.94), 0.259e | 47 (92.2) | 0.836 | 0.88; 0.13–6.13, 0.895e |
40 mg once daily | 19 (63.3) | 28 (29.3) | ||||
50 mg once daily | 4 (100)f | 4 (100)f |
Progression-free survival
Characteristics | Patients, No. (%) | mPFS (months) | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | |||
EGFR mutation subtype, No. (%) | ||||||
Exon 19 deletion | 68 (80.0) | 16.0 | 0.31 (0.14–0.71)a | 0.006 | 0.27 (0.12–0.58)a | 0.001 |
Exon 21 L858R point mutation | 11 (12.9) | 8.7 | 0.34 (0.13–0.94)b | 0.037 | 0.39 (0.15–1.03)b | 0.058 |
Rare and complex mutation | 6 (7.1) | 9.0 | ||||
Baseline symptomatic brain metastases, No. (%) | ||||||
No | 60 (70.6) | 14.3 | 0.67 (0.34–1.27)g | 0.209 | 0.70 (0.37–1.32)g | 0.267 |
Yes | 25 (29.4) | 13.5 | ||||
ECOG performance status, No. (%) | ||||||
0–1 | 69 (81.2) | 13.8 | 0.86 (0.39–1.90)g | 0.703 | 0.86 (0.39–1.90)g | 0.703 |
2–4 | 16 (18.8) | 15.9 | ||||
Abnormal organ function, No. (%) | ||||||
No | 70 (82.4) | 14.3 | 0.53 (0.25–1.09)g | 0.086 | 0.50 (0.25–1.00)g | 0.050 |
Yes | 15 (17.6) | 8.8 | ||||
Afatinib dose adjustment, No. (%) | ||||||
Dose reduced | 26 (30.6) | 15.9 | 0.93 (0.44–1.99)c | 0.854 | 0.72 (0.39–1.34)c | 0.301 |
Dose increased | 10 (11.8) | 13.5 | 2.35 (0.86–6.47)d | 0.098 | 2.13 (0.93–4.88)d | 0.075 |
Starting dose maintained | 49 (57.6) | 13.4 | ||||
Optimal afatinib dose, No. (%) | ||||||
Less than 40 mg once daily | 51 (60.0) | 15.9 | 0.64 (0.32–1.28)e | 0.209 | 0.47 (0.21–1.08)e | 0.075 |
50 mg once daily | 4 (4.7) | 13.5 | 0.97 (0.25–3.78)f | 0.962 | 1.03 (0.27–4.01)f | 0.962 |
40 mg once daily | 30 (35.3) | 13.4 |
Overall survival
Resistance to afatinib
Side-effects of afatinib treatment
CTCAE grade | Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
---|---|---|---|---|---|
Diarrhea, No. (%) | 39 (45.9) | 25 (29.4) | 17 (20.0) | 4 (4.7) | 0 |
Stomatitis, No. (%) | 62 (72.9) | 13 (15.3) | 8 (9.4) | 2 (2.4) | 0 |
Acne/rash, No. (%) | 25 (29.4) | 35 (41.2) | 20 (23.5) | 5 (5.9) | 0 |
Paronychia, No. (%) | 51 (60.0) | 23 (27.1) | 8 (9.4) | 3 (3.5) | 0 |
Fatigue, No. (%) | 71 (83.5) | 13 (15.3) | 1 (1.2) | 0 | 0 |
Side-effects, No (%) | 17 (20.0) | 59 (69.4) | 9 (10.6) |