Activity of the Hsp90 inhibitor Luminespib Among Non-Small Cell Lung Cancers Harboring EGFR Exon 20 Insertions

Abstract

Background

There are currently no approved targeted therapies for NSCLC patients with EGFR exon 20 insertions (ins20), a subgroup of EGFR mutations which are generally refractory to 1^st/2^nd generation EGFR inhibitors. We report the final results of a phase II trial evaluating the activity of the Hsp90 inhibitor luminespib (AUY922) in NSCLC patients with EGFR ins20.

Patients and Methods

29 patients with stage IV NSCLC with EGFR ins20 identified on local testing and at least one prior therapy were enrolled on the trial between 8/2013 and 10/2016. The primary endpoint was objective response rate (ORR), with a pre-determined target rate of effectiveness (defined as the rate of partial response (PR) plus stable disease (SD) lasting ≥ 3 months) of 20%. Secondary endpoints were PFS, OS, safety and response by EGFR ins20 subtype.

Results

Among the 29 patients (18 female, median age 60 years,) the ORR was 17%, median progression-free survival (mPFS) was 2.9 mos (95% CI, 1.4-5.6,) and mOS was 13 mos (95% CI, 4.9-19.5.) The results exceeded the pre-determined target rate of effectiveness with 11/29 (38%) patients having a PR or SD ≥ 3 months. The most common luminespib-related toxicities were diarrhea (83%,) visual changes (76%) and fatigue (45%). All study treatment was stopped on 2/28/17 due to dissolution of study drug availability; 3 patients were on treatment at study termination.

Conclusion

The study met its primary endpoint, suggesting that luminespib may be an active therapy for advanced NSCLC patients with EGFR ins20. Luminespib is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of luminespib and other hsp90 inhibitors in this population is warranted.