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M.S. Huberman
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MINI 30 - New Kinase Targets (ID 157)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:K. Park, M. Villalona
- Coordinates: 9/09/2015, 18:30 - 20:00, Four Seasons Ballroom F3+F4
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MINI30.06 - Activity of AUY922 in NSCLC Patients With EGFR Exon 20 Insertions (ID 1744)
18:30 - 20:00 | Author(s): M.S. Huberman
- Abstract
- Presentation
Background:
EGFR exon 20 insertions (ins20) represent a rare subtype (4%) of EGFR mutations and are refractory to EGFR-specific tyrosine kinase inhibitors (TKIs). No effective targeted therapies exist for patients (pts) with ins20; median PFS on the irreversible EGFR TKI Afatinib is 2.8 months (mos). Based on a durable RECIST partial response (PR) to AUY922, a Heat Shock Protein 90 (Hsp90) inhibitor, observed in an EGFR ins20 patient in a previous study (NCT01124864), we designed a phase II investigator-initiated trial to assess the activity of AUY922 in NSCLC pts with EGFR ins20. Since pts with these mutations are rare, we identified other international investigators who have treated ins20 patients with AUY922. Here, we present the results of a pooled international experience of 21 patients with EGFR ins20 treated with AUY922 in the United States, Taiwan and the Netherlands.
Methods:
A total of 21 patients with EGFR in20 are included in this analysis. 14 were treated on a single-arm, multi-center, open-label study of AUY922 in advanced NSCLC pts with EGFR ins20 mutations in the US (NCT01854034). Five were treated on a multicenter Taiwanese trial of AUY922 across a variety of molecular NSCLC subtypes (NCT01922583) and two were treated on a compassionate-use basis in the Netherlands. The starting dose of AUY922 was 70mg/m2 IV weekly for all patients.
Results:
21 pts, including 14 females and 7 males, average age 55 (range, 27-75) were included in this analysis. The median number of prior therapies was 2 (range, 1-6.) 6 pts received a prior EGFR TKI; none responded to TKI monotherapy. The most common AUY922-related toxicities were grade 1-2 visual changes (18/21; 86%) diarrhea (18/21; 86%) and fatigue (15/21; 71%). The only treatment-related grade 3 toxicities was hypertension (2/21; 1%) and AST elevation (1/21; 0.5%). There was one death on study, related to pre-existing comorbidity/unrelated to AUY922. Among the 21 patients treated, 5 achieved a partial response by RECIST 1.1 (ORR 24%) (Figure 1.) The median PFS estimate is 3.9 mos (95% CI, 2.9 to 10.7.) 6 patients remain on treatment at the time of abstract submission. Updated results and correlation with specific ins20 mutations will be presented. Figure 1
Conclusion:
This international experience suggests that AUY922 may be an active therapy for advanced NSCLC pts with EGFR ins20 mutations with an ORR 24% and median PFS 3.9 mo. AUY922 is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of AUY922 in this population is warranted.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-027 - Targeted next Generation Sequencing in Lung Cancer: Genomic Oncology in Daily Practice (ID 103)
09:30 - 17:00 | Author(s): M.S. Huberman
- Abstract
Background:
Tumor genotyping using single gene assays (SGAs) is a standard approach in the management of advanced NSCLC. We evaluated how therapeutic decision-making was altered by the introduction of next generation sequencing (NGS) into routine clinical practice.
Methods:
Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution.
Results:
82 tumors were genotyped: 75 by SGAs, 7 by NGS alone, and 22 by SGAs and NGS. SGAs identified 10 EGFR-mutated, 3 ALK-rearranged, and 21 KRAS-mutated tumors. Sequential testing with SGAs followed by NGS was more common for patients with EGFR/ALK/KRAS-negative tumors (22/29 or 75.9%) and adenocarcinomas (ACs) (21/22 or 95.5%). Most EGFR/ALK/KRAS-negative tumors were sent for NGS (21/35 or 60%). Of 17 ACs, 10 harbored abnormalities in a known driver oncogene (1-EGFR, 2-ERBB2, 1-ROS1, 1-RET, 2-MET, 2-KRAS and 1-MAP2K1). Primary NGS was used mainly in squamous cell cancers (SCCAs) (6/7 or 85.7%). In 7 SCCAs, 1 sample had a driver aberration (FGFR1); 6 had other genomic events (all with TP53 mutations). NGS was successful in 24/29 (82.7%) tumors overall. There was a trend toward increased assay failure in those samples undergoing sequential SGAs followed by NGS as compared to primary NGS alone. All patients with EGFR-mutated or ALK-rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. Clinical decisions were impacted by NGS results in 8/17 (47.0%) ACs (trial consideration in 6, off-label TKI use in 2). Therapeutic decisions were influenced by NGS results in 0/7 SCCAs (p=0.0538 when compared to ACs). Actionable therapeutic targets were significantly more frequent in patients with a ≤15 pack-year tobacco history vs. those with >15 pack-years of tobacco use (17/27 or 62.9% vs. 3/42 or 7.1%, respectively; p<0.0001). Only 1/9 (11%) of oncologists demonstrated a detailed understanding of the genomic technologies being used. Figure 1
Conclusion:
Targeted NGS can identify a significant number of driver events in lung ACs—particularly in never/light smokers—for which targeted therapies are available or in development. However, for SCCAs, NGS results are less likely to alter standard practice, barring participation in biomarker-driven studies. Future research into the cost effectiveness and optimal use of NGS in NSCLC is warranted, as well as continued efforts to improve provider awareness and application of genomic technologies.
