Abstract 1357P
Background
Mutations in exon (ex) 19 or 21 comprise > 90% of EGFR mutations (mut). Presence of these EGFR mut in NSCLC is associated with sensitivity to EGFR tyrosine kinase inhibitors (TKI). This systematic literature review provides a contemporary overview of available literature evaluating the outcomes of first-line (1L) EGFR-targeted treatments by these two EGFR mut subtypes.
Methods
Medline, EMBASE, Cochrane Central Register of Controlled Trials (CCRCT) and Cochrane Database of Systematic Reviews (CDSR) were searched in March 2019 to identify randomized controlled trials (RCTs) of pharmacological treatments in the 1L setting for advanced EGFR mutated NSCLC and corresponding efficacy, safety and quality of life (QoL) data. Clinical trial registries and non-indexed conference abstracts were searched manually. PRISMA standards were followed. Here, we report ex 19 and 21 subgroup data.
Results
A total of 25 publications (from 20 RCTs), reported median progression-free survival (mPFS) for the ex 19 and 21 EGFR mut subgroups while 13 publications (from 11 RCTs) reported median overall survival (mOS). The 13 studies reporting both mPFS and hazard ratio (HR) are shown in the table. Where TKI therapy was the control group (CG), mOS for ex 19 ranged from 26.4 – 45.7 months (mo) with 4 of 7 publications reporting HRs (range: 0.82 - 2.36; none significant at p < 0.05). For ex 21, mOS ranged from 21.2 - 41.3 mo with no significant HRs (range: 0.71 – 1.23). Safety and QoL were not identified. Table: 1357P
| Trial | Ex 19 | Ex 21 | ||||
| mPFS versus (v) CG, mo | ΔPFS | HR (*p < 0.05) | mPFS v CG, mo | ΔPFS | HR (*p < 0.05) | |
| v chemotherapy | ||||||
| CONVINCE | 11.2 v 8.0 | 3.2 | 0.66 | 11.1 v 7.8 | 3.3 | 0.76 |
| ENSURE | 11.1 v 4.2 | 6.9 | 0.20* | 8.3 v 7.1 | 1.2 | 0.57 |
| EURTAC | 11.0 v 4.6 | 6.4 | 0.30* | 8.4 v 6.0 | 2.4 | 0.55 |
| IPASS | 11.0 v 6.9 | 4.1 | 0.43* | 8.6 v 7.7 | 0.9 | 0.81 |
| LUX-Lung 3 | 16.4 v 3.1 | 13.3 | 0.16* | 13.7 v 8.3 | 5.4 | 0.50 |
| LUX-Lung 6 | 13.7 v 5.6 | 8.1 | 0.21* | 8.3 v 5.6 | 2.7 | 0.33* |
| WJTOG3405 | 9.0 v 6.0 | 3.0 | 0.45* | 9.6 v 6.7 | 2.9 | 0.51* |
| v EGFR TKI | ||||||
| RELAY | 19.6 v 12.5 | 7.1 | 0.65* | 19.4 v 11.2 | 8.2 | 0.62* |
| ARCHER 1050 | 16.5 v 9.2 | 7.3 | 0.55 | 12.3 v 9.8 | 2.5 | 0.63 |
| FLAURA | 21.4 v 11.0 | 10.4 | 0.43* | 14.4 v 9.5 | 4.9 | 0.51* |
| JO25567 | 18.0 v 10.3 | 7.7 | 0.41* | 13.9 v 7.1 | 6.8 | 0.67 |
| LUX-Lung 7 | 12.7 v 11.0 | 1.7 | 0.76 | 10.9 v 10.8 | 0.1 | 0.71 |
| NCT01221077 | 8.4 v 12.9 | -4.5 | 2.09 | 9.4 v 11.7 | -2.3 | 0.83 |
Conclusions
While several RCTs (as seen in the table) reported consistent PFS benefit across ex 19 and 21 subtypes, an overall trend suggested better treatment effects in patients with ex 19 EGFR mut. Further understanding of outcomes associated with these EGFR mut in NSCLC will better inform clinical decisions and optimal selection of 1L treatment.
Clinical trial identification
Editorial acknowledgement
Hannah Davis, PhD, an Eli Lilly and Company employee, provided medical writing support.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
K.B. Winfree, U. Kiiskinen, G. Reppen, K. Taipale, C. Molife, M-H. Jen, S. Traore, R. Varea: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly & Company. All other authors have declared no conflicts of interest.