mutation status was prospectively determined for screening and enrollment of patients by a clinical trial assay (CTA). Tumor samples from 264 patients (178 randomized to Gilotrif and 86 patients randomized to chemotherapy) were tested retrospectively by the companion diagnostic therascreen® EGFR RGQ PCR Kit, which is FDA-approved for selection of patients for Gilotrif treatment.
Among the patients randomized, 65% were female, the median age was 61 years, the baseline ECOG performance status was 0 (39%) or 1 (61%), 26% were Caucasian and 72% were Asian. The majority of the patients had a tumor sample with an EGFR mutation categorized by the CTA as either exon 19 deletion (49%) or exon 21 L858R substitution (40%), while the remaining 11% had other mutations.
A statistically significant improvement in PFS as determined by the IRC was demonstrated for patients randomized to Gilotrif compared with those randomized to chemotherapy. See Table 3 and Figure 1. There was no statistically significant difference for overall survival between the treatment arms at the interim analysis conducted at 84% of the planned events for the final analysis.
Table 3: Efficacy Results of Study 1
Gilotrif
(N=230) Pemetrexed/Cisplatin
(N=115)
Progression-free Survival
Number of Deaths or Progressions, N (%) 152 (66.1%) 69 (60.0%)
Median Progression-free Survival (months) 11.1 6.9
95% CI (9.6, 13.6) (5.4, 8.2)
HR (95% CI) 0.58 (0.43, 0.78)
Stratified Log-Rank Test P-value* <0.001
Overall Survival
Number of Deaths, N (%) 116 (50.4%) 59 (51.2%)
Median Overall Survival (months) 28.1 28.2
95% CI (24.6, 33.0) (20.7, 33.2)
HR (95% CI) 0.91 (0.66, 1.25)
Stratified Log-Rank Test P-value* 0.55
Objective Response Rate (CR + PR)
N (%) 116 (50.4%) 22 (19.1%)
Response Duration
Median (months) 12.5 6.7
Stratified by EGFR mutation status and race.
CR=complete response; PR=partial response
Subgroup analyses were conducted based on the stratification factor of EGFR mutation status (Del19, L858R, other) and mutation category (common [Del19, L858R] vs uncommon [other]). See Figure 2
There were 26 Gilotrif-treated patients in the “other” (uncommon) EGFR mutations subgroup with nine unique mutation patterns. None of these 26 patients achieved a complete response, while four achieved a partial response (see Table 4 below). No responses were seen in Gilotrif-treated patients with the following mutations: T790M alone (n=2), deletion 19 and T790M (n=3), G719X and T790M (n=1), exon 20 insertion (n=6), and L861Q alone (n=3). There were 11 chemotherapy-treated patients in the “other” uncommon EGFR mutation subgroup; of these, four (36%) achieved a part |
