Table 5.
Factors affecting overall survival during first- and second-line treatments
| 1′ Afatinib → 2′ Osimertinib (n=166) |
1′ Afatinib → 2′ Other therapies (n=235) |
|||||||
|---|---|---|---|---|---|---|---|---|
| Univariable |
Multivariable |
Univariable |
Multivariable |
|||||
| HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | |
| Sex | ||||||||
| Male | 1 | - | 1 | 1 | ||||
| Female | 1.33 (0.81–2.19) | 0.253 | 0.70 (0.47–1.04) | 0.080 | 0.76 (0.50–1.17) | 0.210 | ||
| Age (yr) | ||||||||
| < 65 | 1 | - | 1 | - | ||||
| ≥ 65 | 0.85 (0.51–1.43) | 0.541 | 1.11 (0.74–1.64) | 0.618 | ||||
| BMI (kg/m 2 ) | ||||||||
| < 23.0 | 1 | - | 1 | - | ||||
| 23.0 to < 25.0 | 0.37 (0.11–1.28) | 0.115 | 1.27 (0.55–2.91) | 0.573 | ||||
| ≥ 25.0 | 0.70 (0.33–1.52) | 0.369 | 1.05 (0.49–2.24) | 0.909 | ||||
| ECOG PS | ||||||||
| 0 or 1 | 1 | 1 | 1 | - | ||||
| ≥ 2 | 3.1 (1.22–7.83) | 0.017 | 2.79 (1.01–7.71) | 0.047 | 1.44 (0.70–2.98) | 0.324 | ||
| Smoking | ||||||||
| Never | 1 | - | 1 | - | ||||
| Former | 1.23 (0.72–2.10) | 0.457 | 0.95 (0.60–1.52) | 0.838 | ||||
| Current | 0.57 (0.22–1.46) | 0.244 | 1.30 (0.65–2.60) | 0.468 | ||||
| Stage a) | ||||||||
| 3 and 4A | 1 | 1 | 1 | 1 | ||||
| 4B | 1.61 (0.97–2.68) | 0.065 | 0.71 (0.30–1.72) | 0.450 | 1.58 (1.05–2.38) | 0.028 | 1.19 (0.72–1.97) | 0.493 |
| T category | ||||||||
| T1 | 1 | - | 1 | - | ||||
| T2 | 1.08 (0.39–2.97) | 0.887 | 1.35 (0.53–3.43) | 0.529 | ||||
| T3 | 1.65 (0.43–6.39) | 0.469 | 2.43 (0.70–8.37) | 0.161 | ||||
| T4 | 3.49 (1.37–8.97) | 0.009 | 2.68 (1.06–6.73) | 0.036 | ||||
| N category | ||||||||
| N0 | 1 | - | 1 | - | ||||
| N1 | 0.89 (0.23–3.47) | 0.872 | 0.89 (0.17–4.62) | 0.890 | ||||
| N2 | 0.75 (0.23–2.41) | 0.626 | 2.89 (0.93–8.99) | 0.066 | ||||
| N3 | 1.44 (0.58–3.54) | 0.433 | 3.65 (1.36–9.81) | 0.010 | ||||
| M category | ||||||||
| M0 | 1 | - | 1 | - | ||||
| M1a | 1.24 (0.28–5.61) | 0.777 | 1.84 (0.41–8.22) | 0.426 | ||||
| M1b | 1.08 (0.19–5.98) | 0.928 | 4.29 (0.80–20.39) | 0.067 | ||||
| M1c | 2.21 (0.49–9.89) | 0.298 | 4.38 (0.99–19.39) | 0.051 | ||||
| Tissue type | ||||||||
| Adenocarcinoma | 1 | - | 1 | - | ||||
| Others | 3.09 (0.75–12.75) | 0.120 | 2.68 (0.65–10.96) | 0.171 | ||||
| EGFR | ||||||||
| Del19 | 1 | - | 1 | 1 | ||||
| L858R | 1.37 (0.80–2.32) | 0.249 | 1.27 (0.81–2.00) | 0.293 | 1.41 (0.89–2.22) | 0.146 | ||
| Othersb) | 1.45 (0.64–3.28) | 0.371 | 1.90 (1.12–3.21) | 0.017 | 1.88 (1.08–3.28) | 0.026 | ||
| No. of metastatic organs | ||||||||
| 0–1 | 1 | 1 | 1 | |||||
| 2–3 | 1.86 (1.08–3.21) | 0.025 | 1.15 (0.49–2.72) | 0.750 | 2.12 (1.40–3.21) | < 0.001 | 1.57 (0.88–2.79) | 0.128 |
| 4 or more | 3.26 (1.55–6.87) | 0.002 | 1.74 (0.49–6.21) | 0.395 | 3.27 (1.45–7.39) | 0.004 | 2.03 (0.68–6.08) | 0.204 |
| Brain metastasis | ||||||||
| No | 1 | 1 | 1 | - | ||||
| Yes | 1.68 (1.01–2.80) | 0.047 | 1.75 (0.86–3.58) | 0.122 | 1.29 (0.86–1.91) | 0.217 | ||
| Adrenal gland metastasis | ||||||||
| No | 1 | - | 1 | - | ||||
| Yes | 0.47 (0.15–1.49) | 0.201 | 1.63 (0.79–3.37) | 0.190 | ||||
| Lung to lung metastasis | ||||||||
| No | 1 | - | 1 | - | ||||
| Yes | 1.06 (0.64–1.77) | 0.815 | 1.03 (0.68–1.57) | 0.889 | ||||
| Liver metastasis | ||||||||
| No | 1 | 1 | 1 | 1 | ||||
| Yes | 3.69 (2.03–6.72) | < 0.001 | 2.04 (0.92–4.57) | 0.081 | 2.62 (1.42–4.82) | 0.002 | 1.89 (0.92–3.89) | 0.084 |
| Bone metastasis | ||||||||
| No | 1 | 1 | 1 | 1 | ||||
| Yes | 1.74 (1.06–2.86) | 0.029 | 1.19 (0.51–2.77) | 0.686 | 1.87 (1.25–2.81) | 0.002 | 1.20 (0.69–2.07) | 0.519 |
| Pericardial metastasis | ||||||||
| No | 1 | 1 | 1 | 1 | ||||
| Yes | 2.26 (0.97–5.28) | 0.060 | 2.08 (0.69–6.34) | 0.195 | 2.49 (1.08–5.72) | 0.032 | 1.42 (0.56–3.60) | 0.464 |
| Pleural metastasis | ||||||||
| No | 1 | - | 1 | - | ||||
| Yes | 0.89 (0.54–1.47) | 0.646 | 1.05 (0.71–1.57) | 0.810 | ||||
| Type of brain metastasis | ||||||||
| Single parenchymal | 1 | - | 1 | - | ||||
| Multiple +/− seeding | 1.16 (0.34–3.92) | 0.810 | 0.97 (0.46–2.06) | 0.944 | ||||
| New lesion or aggravation of brain metastasis | ||||||||
| No | 1 | 1 | 1 | - | ||||
| Yes | 2.05 (1.16–3.61) | 0.013 | 1.68 (0.83–3.40) | 0.146 | 1.24 (0.79–1.95) | 0.343 | ||
| Dose adjustment for afatinib | ||||||||
| Yes | 1 | - | 1 | 1 | ||||
| No | 0.75 (0.44–1.29) | 0.303 | 1.56 (1.05–2.32) | 0.027 | 1.61 (1.05–2.48) | 0.029 | ||
AJCC, American Joint Committee on Cancer; BMI, body mass index; CI, confidence interval; Del19, deletion 19; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; HR, hazard ratio.
a)
Tumor stage was evaluated based on the 8th edition of the AJCC staging manual,
b)
Other types of EGFR mutation include compound and uncommon mutations.