Phase 2 Study of the HSP-90 Inhibitor AUY922 in Previously Treated and Molecularly Defined Patients with Advanced Non–Small Cell Lung Cancer

Enriqueta Felip, Fabrice Barlesi, Benjamin Besse, Quincy Chu, Leena Gandhi, Sang-We Kim, Enric Carcereny, Lecia V. Sequist, Paal Brunsvig, Christos Chouaid, Egbert F. Smit, Harry J. M. Groen, Dong-Wan Kim, Keunchil Park, Emin Avsar, Sebastian Szpakowski, Mikhail Akimov, Edward B. Garon

Research output: Contribution to journalArticleAcademicpeer-review


Introduction: In this phase 2 study, we evaluated the activity of AUY922 in pretreated patients with stage IV NSCLC. Methods: Patients with advanced NSCLC were divided into molecularly defined strata based on mutations in the EGFR gene, the ALK receptor tyrosine kinase gene (ALK), the KRAS gene, or the wild type of all three. All patients must have received more than two prior lines of therapy, except for those in a fifth stratum for a less pretreated EGFR cohort (EGFR<2). In the EGFR-mutant and ALK-rearranged strata, prior platinum therapy was not required. Patients with EGFR mutation must have received an EGFR tyrosine kinase inhibitor unless they had de novo resistance (e.g., T790M or exon 20 insertions). Eligible patients received weekly intravenous AUY922, 70 mg/m2. The primary objective was to estimate efficacy (complete or partial response, or in the absence of complete or partial response, stable disease) at 18 weeks, by the Response Criteria in Solid Tumors. Results: A total of 153 patients from 21 global centers were enrolled from October 2010 to November 2014. The investigator-assessed overall response rate and stable disease rate at 18 weeks were 31.8% and 9.1% in the ALK-rearranged stratum, 17.1% and 8.6% in EGFR-mutant stratum, 9.7% and 22.6% in the EGFR<2 stratum, 0% and 7.1% in KRAS-mutant stratum, and 8.8% and 8.8% in wild-type stratum. Biomarker data showed activity of AUY922 in EGFR-mutant patients with exon 19 deletion, T790M mutation, and exon 20 insertion. The most common (≥40%) all-causality adverse events were diarrhea, nausea, and decreased appetite. Visual-related disorders were reported in 79.7% of patients (most were grade 1/2). Thirty-five patients (22.9%) reported night blindness. Conclusion: AUY922 is active in patients with NSCLC, particularly among patients with ALK rearrangements and EGFR mutations.
Original languageEnglish
Pages (from-to)576-584
Number of pages9
JournalJournal of Thoracic Oncology
Issue number4
Publication statusPublished - 2018

Cite this