TABLE 3.
Objective Response Rates, Disease Control Rates, and Survival Hazard Ratios (HRs) With Gefitinib Versus Placebo for EGFR Protein Expression (Percent of Positive Staining) With Dako PharmDx Kit
| EGFR staining cutoff level | EGFR subgroup | No. of patients | No. of deaths | Survival HR (95% CI)* | Interaction test P | Gefitinib responders No. (%) | Placebo responders No. (%) | Gefitinib disease control rate No. (%) | Placebo disease control rate No. (%) |
|---|---|---|---|---|---|---|---|---|---|
| EGFR cutoff 1 | EGFR+ | 271 | 167 | 0.78 (0.56–1.08) | .067 | 13 (8) | 1 (1.5) | 60 (36.8) | 26 (38.8) |
| EGFR cutoff 1 | EGFR− | 108 | 65 | 1.51 (0.82–2.77) | 1 (1.6) | 0 (0) | 18 (28.1) | 10 (34.5) | |
| EGFR cutoff 10 | EGFR+ | 264 | 166 | 0.77 (0.56–1.08) | .049 | 13 (8.2) | 1 (1.5) | 57 (36.1) | 25 (37.9) |
| EGFR cutoff 10 | EGFR− | 115 | 66 | 1.57 (0.86–2.87) | 1 (1.4) | 0 (0) | 21 (30.4) | 11 (36.7) | |
| EGFR cutoff 20 | EGFR+ | 249 | 156 | 0.79 (0.56–1.11) | .114 | 13 (8.7) | 1 (1.7) | 55 (36.7) | 21 (35) |
| EGFR cutoff 20 | EGFR− | 130 | 76 | 1.42 (0.82–2.44) | 1 (1.3) | 0 (0) | 23 (29.9) | 15 (41.7) | |
| EGFR cutoff 30 | EGFR+ | 221 | 138 | 0.77 (0.53–1.11) | .129 | 13 (9.4) | 1 (2) | 54 (38.8) | 16 (31.4) |
| EGFR cutoff 30 | EGFR− | 158 | 94 | 1.27 (0.8–2) | 1 (1.1) | 0 (0) | 24 (27.3) | 20 (44.4) | |
| EGFR cutoff 40 | EGFR+ | 198 | 124 | 0.75 (0.51–1.1) | .135 | 12 (9.6) | 1 (2.2) | 53 (42.4) | 14 (30.4) |
| EGFR cutoff 40 | EGFR− | 181 | 108 | 1.24 (0.81–1.9) | 2 (2) | 0 (0) | 25 (24.5) | 22 (44) | |
| EGFR cutoff 50 | EGFR+ | 171 | 111 | 0.84 (0.56–1.28) | .555 | 10 (9.3) | 1 (2.4) | 43 (39.8) | 14 (33.3) |
| EGFR cutoff 50 | EGFR− | 208 | 121 | 1.08 (0.72–1.63) | 4 (3.4) | 0 (0) | 35 (29.4) | 22 (40.7) | |
| EGFR cutoff 60 | EGFR+ | 142 | 94 | 1.01 (0.63–1.61) | .756 | 8 (8.7) | 1 (3.1) | 37 (40.2) | 10 (31.3) |
| EGFR cutoff 60 | EGFR− | 237 | 138 | 0.97 (0.67–1.41) | 6 (4.4) | 0 (0) | 41 (30.4) | 26 (40.6) | |
| EGFR cutoff 70 | EGFR+ | 116 | 81 | 1.01 (0.62–1.65) | .802 | 7 (9.5) | 1 (3.4) | 30 (40.5) | 9 (31) |
| EGFR cutoff 70 | EGFR− | 263 | 151 | 0.99 (0.69–1.41) | 7 (4.6) | 0 (0) | 48 (31.4) | 27 (40.3) | |
| EGFR cutoff 80 | EGFR+ | 83 | 60 | 1.01 (0.57–1.78) | .857 | 6 (11.5) | 0 (0) | 20 (38.5) | 4 (21.1) |
| EGFR cutoff 80 | EGFR− | 296 | 172 | 0.96 (0.69–1.34) | 8 (4.6) | 1 (1.3) | 58 (33.1) | 32 (41.6) | |
| EGFR cutoff 90 | EGFR+ | 65 | 44 | 0.85 (0.43–1.68) | .760 | 4 (10) | 0 (0) | 17 (42.5) | 1 (7.1) |
| EGFR cutoff 90 | EGFR− | 314 | 188 | 0.99 (0.72–1.37) | 10 (5.3) | 1 (1.2) | 61 (32.6) | 35 (42.7) | |
| EGFR unknown | — | 1313 | 744 | 0.84 (0.73–0.98) | — | 63 (8.6) | 5 (1.3) | 303 (41.4) | 118 (30.7) |
| All patients | — | 1692 | 976 | 0.86 (0.76–0.99) | — | 77 (8) | 6 (1.3) | 381 (39.7) | 154 (32.1) |
EGFR indicates epidermal growth factor receptor; CI, confidence interval.
*
From Cox regression analysis with stratification factors; HR < 1 are in favor of gefitinib.