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Found 1 Presentation For Request "1142P"
1142P - Treatment of metastatic uveal melanoma (mUM) through genomic profiling
- Serge Leyvraz (Berlin, Germany)
Abstract
Background
There is no standard treatment for mUM. A high-throughput genomic and transcriptomic program was initiated to uncover potential targets and assign molecularly guided treatment to this “hard-to-treat” tumor.
Methods
From March 2016 to November 2019 mUM patients were included in the prospective Treat20Plus study and tumor was analyzed via a comprehensive molecular tumor analysis program. A molecular tumor board interpreted the data and issued treatment recommendations.
Results
Forty-four patients were included: 25F/19M, age: 61(24-80), ECOG: 0 (0-2), time to metastasis 3.7 years (0-36), metastatic sites: 5 (1-8), abnormal LDH: 68%, pretreated patients: 63%. Tumor cell content was too low in 6. Time from biopsy to analysis: 59 days (28-144). Mutation burden: 32 (15-459). The genetic alterations affected GNAQ (15), GNA11 (23), BAP1 (19), SF3B1 (14), EIF1AX (1), BAP1 and SF3B1 (1), PTEN (5) and NF1 (1). In addition, we found MYC gain (32), up-regulation of MET (27), BCL2 (32) and MDM2 (11). Thirty-nine patients had a treatment recommendation and 25 (64%) of them received a targeted therapy accordingly, based on off-label use of trametinib (14), selumetinib (2), crizotinib (7), cabozantinib (4), palbociclib (1), sorafenib+trametinib (1). We documented a minor response in one patient, a mixed response in 2, and a stable disease in 9. One patient with 459 somatic mutations and a MBD4 mutation had a partial durable response under Nivolumab. The median duration of the clinical benefit was 10 months (6-17). Median PFS was 3.33 months (95% CI: 0-7.21). It was significantly related to LDH and MYC status. Median OS was 12.47 months (95% CI: 7.33-17.63). It was significantly dependent on LDH, number of metastatic sites and MYC, in multivariate analysis. Overall, the targeted treatment had no significant influence on survival.
Conclusions
This precision oncology program was successful with more than half of the patients receiving a treatment based on molecular recommendations.
Legal entity responsible for the study
Charité Comprehensive Cancer Center, Berlin, Germany Max-Planck-Institut für molekulare Genetik, Berlin, Germany.
Funding
Bundesministerium für Bildung und Forschung, Germany Max-Planck-Institut für Molekulare Genetik, Berlin, Germany Charité Comprehensive Cancer Center, Berlin, Germany.
Disclosure
S. Leyvraz: Advisory/Consultancy: Bayer; Travel/Accommodation/Expenses: Bayer. D.T. Rieke: Advisory/Consultancy: Alacris Theranostics; Honoraria (self): Bayer; Honoraria (self): Bristol-Myers-Squibb. C. Ulrich: Research grant/Funding (institution), Travel/Accommodation/Expenses: Regeneron; Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis. U. Keilholz: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer. All other authors have declared no conflicts of interest.