Luminespib May Be Effective in NSCLC With EGFR Exon 20 Insertion Mutation

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Exon 20 mutations account for 4% to 10% of EGFR mutations in NSCLC and are refractory to EGFR TKIs; there are no targeted therapies available for this patient population.
Exon 20 mutations account for 4% to 10% of EGFR mutations in NSCLC and are refractory to EGFR TKIs; there are no targeted therapies available for this patient population.
The following article features coverage from the IASLC 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan. Click here to read more of Cancer Therapy Advisor's conference coverage.

Luminespib demonstrated clinical activity and a favorable safety profile among patients with advanced non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, according to research presented at the International Association for the Study of Lung Cancer (IASLC) 18th Annual World Conference on Lung Cancer (WCLC) in Yokohama, Japan.1

EGFR exon 20 mutations account for 4% to 10% of EGFR mutations in NSCLC and are refractory to EGFR TKIs; there are no targeted therapies available for this patient population.

For this phase 2 study (ClinicalTrials.gov Identifier: NCT01854034), researchers enrolled 29 patients with NSCLC to receive IV luminespib 70 mg/m2 once weekly. Eligible patients had confirmed EGFR exon 20 mutations, had an ECOG performance status of 0 to 2, and were previously treated with at least 1 line of treatment.

The overall response rate (ORR) was 17%, with 4 patients displaying a partial response (PR) and 1 patient displaying a complete response (CR). Nine patients had progressive disease and 15 patients had stable disease.

Median overall survival was 13 months (95% CI, 4.9-19.5), and median progression-free survival (PFS) was 2.9 months (95% CI, 1.4-5.6).

Patients with a performance status of 0 or 1 and who had previously received only 1 line of treatment had an ORR of 21% and a median PFS of 5.1 months (95% CI, 2.1-11.8).

The most frequently reported adverse events (AEs) were visual changes, diarrhea, and fatigue; grade 3 AEs included ocular toxicity, hypertension, and hypophosphatemia.

The authors concluded that “[f]urther study of luminespib and other Hsp90 inhibitors in this population is warranted, as are novel systems to continue drug supply for benefitting patients when availability experimental compounds is limited.”

Read more of Cancer Therapy Advisor's coverage of the IASLC 18th World Conference on Lung Cancer (WCLC) by visiting the conference page.

Reference

  1. Piotrowska Z, Costa DB, Huberman M, et al. Final results of a phase 2 study of the hsp90 inhibitor luminespib (AUY922) in NSCLC patients harboring EGFR exon 20 insertion. Presented at: International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer; Yokohama, Japan: October 15-18, 2017. Abstract OA 12.02.

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