Abstract B29: Analysis of Clinical Cancer Gene Panels by Next Generation Sequencing in Tumor and Circulating Cell-Free DNA Samples in Recurrent Ovarian Cancer Patients
Authors: Londono Angelina I. , Farrukh Naveed , Smith Mary Kat , Tawfik Cindy M. , Alvarez Ronald D. , Huh Warner K. , Bevis Kerri S. , Leath Charles A. , Michael Straughn , Yang Eddy Shih Hsin , Harada Shuko , Kim Kenneth H. , Arend Rebecca C. 
Published: December 2017

Objective: We investigated the potential role of molecular profiling through next generation sequencing (NGS) to identify actionable gene mutations in tumors of recurrent ovarian cancer patients that could impact clinical care decisions.

Methods: Under IRB approval, patients diagnosed with recurrent ovarian cancer from 9/2015 to 3/2016 underwent NGS of archival tumor specimens utilizing a 65 gene panel performed by Washington University's Genomics and Pathology Services (GPS) or a 315 gene FoundationOne (FO) panel performed by Foundation Medicine. Select patients also underwent NGS of circulating cell free DNA (cfDNA) from blood specimens utilizing a 50 gene panel performed at Circulogene Theranostics. Genomic alterations found from cfDNA in the blood at the time of recurrence were compared to alterations found in archival tumor tissue. The effect of therapies selected on the basis of NGS testing was assessed.

Results: Specimens from 95 recurrent ovarian cancer patients have been collected; 54 had the GPS gene panel and 35 had the FO gene panel. Six patient samples were unable to be sequenced due to inadequate tumor DNA. 44 patients were sequenced with the 50 gene cfDNA panel at Circulogene; four patient samples did not have detectable cfDNA and were unable to be sequenced. 30 patients have had both NGS on tumor and cfDNA. A range of 0 to15 mutations were detected by the GPS or FO NGS panel with an average of 3.7 mutations per tumor sample. A range of 0 to 6 mutations were detected on cfDNA panel with an average of 1.7 mutations per patient. The most frequent mutation detected by GPS, FO, and Circulogene was TP53. Of the 30 patients with both tumor and cfDNA sequenced, only 7 patients were found to have a TP53 genomic alteration in both the tumor and cfDNA. In all other patients where both cfDNA and tumor DNA had NGS performed, there was no concordance between the tumor and the cfDNA genomic alterations. Of the 95 patients, three patients were started on targeted therapy based on their results (Olaparib for a somatic BRCA mutation [without a germline mutation], Pazopanib for a FGFR mutation, Everolimus for a CTNNB1 mutation). Targeted therapy is being pursued in 6 additional patients: Trametinib for a patient with a KRAS mutation, Nivolumab for a patient with high microsatellite instability, Everolimus for 3 patients with PIK3CA mutations or a PTEN mutation, and Pertuzumab for a patient with a ERBB3 mutation. A somatic BRCA mutation was found in nine patients, seven of which also have a germline BRCA mutation.

Conclusion: Ovarian cancer has a diverse genetic landscape and molecular profiling via NGS offers the opportunity to identify genetic alterations that can be utilized to direct therapy. Approximately 15% of patients with recurrent ovarian cancer have a mutation that can be targeted with a commercially available drug. We have been successful in providing patients with a mutation the NGS-directed therapy. Challenges still exist with the large variation in NGS technology and reporting and further research is needed to better identify actionable oncogenic drivers.

Citation Format: Angelina I. Londono, Naveed Farrukh, Mary Kat Smith, Cindy M. Tawfik, Ronald D. Alvarez, Warner K. Huh, Kerri S. Bevis, Charles A. Leath, III, Straughn Michael, Jr., Eddy Shih Hsin Yang, Shuko Harada, Kenneth H. Kim, Rebecca C. Arend. Analysis of Clinical Cancer Gene Panels by Next Generation Sequencing in Tumor and Circulating Cell-Free DNA Samples in Recurrent Ovarian Cancer Patients [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr B29.