Abstract 1362P
Background
In EGFR-mutant NSCLC patients, approximately 0.5-4% have exon 20 insertions. Approved EGFR tyrosine kinase inhibitors (TKIs) are ineffective in patients with exon 20 insertions. We reviewed and synthesized published evidence for outcomes in these patients.
Methods
A systematic literature review was performed following PRISMA guidelines. Populations of interest were EGFR-mutant NSCLC patients with exon 20 insertions, including subgroups analyses in larger NSCLC cohorts. Outcomes included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR), all weighted by number of patients in the meta-analysis.
Results
Of 3920 records, 5 clinical and 32 real-world evidence (RWE) studies fulfilled inclusion criteria. Meta-analyzed real-world outcomes for treatment groups (TKI, chemotherapy +/- TKI, and immuno-oncology (IO) agents) were generally suboptimal (Table). Most RWE studies reported outcomes for cohorts with patients at various lines of therapy. In clinical studies, TAK-788 showed promising results with a 43% confirmed ORR (n=12/28) and a 7.3-month median PFS in refractory patients; ORR for JNJ-372 was 30% in TKI-naïve patients (22% confirmed, n =27 ); poziotinib, luminespib, afatinib, and cisplatin/pemetrexed resulted in <20% ORR. In clinical studies that reported brain metastases, the mean rate was 25% (range, 0-53%). Table: 1362P
Outcomes in EGFR-mutant NSCLC patients with exon 20 insertions*
| Median OS, months (n) | Median PFS, months (n) | ORR, % (n) | |
| All treatments | 16.2 (666) | 4.8 (707) | 19.8% (684) |
| TKI | 12.6 (210) | 4.0 (317) | 16.1% (409) |
| Chemotherapy +/- TKI | 18.6 (330) | 5.5 (355) | 27.5% (242) |
| IO agent | 7.5 (29) | 3.2 (26) | 10.0% (30) |
*Includes a mixture of newly diagnosed and RR patients as the majority of studies did not report outcomes by line of therapy
Conclusions
Despite recent treatment advances in EGFR-mutant NSCLC, real-world outcomes remain poor for patients harboring exon 20 insertions. Several agents, currently undergoing clinical evaluation, may help alleviate unmet needs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Millennium Pharmaceuticals, Inc.
Disclosure
D. Tomaras: Full/Part-time employment, Purple Squirrel Economics is a paid consultant to Millennium Pharmaceuticals: Purple Squirrel Economics; Advisory/Consultancy: Millennium Pharmaceuticals Inc. H.M. Lin: Full/Part-time employment: Millennium Pharmaceuticals Inc. A. Forsythe: Full/Part-time employment, Purple Squirrel Economics is a paid consultant to Millennium Pharmaceuticals: Purple Squirrel Economics; Advisory/Consultancy: Millennium Pharmaceuticals Inc. V. Crossland: Full/Part-time employment: Millennium Pharmaceuticals Inc. S-H.I. Ou: Full/Part-time employment, Paid consultant to Millennium Pharmaceuticals: UCI Health; Advisory/Consultancy: Millennium Pharmaceuticals Inc.