Abstract B200: A new resource enabling the practical utility of targeted therapy in oncology clinics.

Abstract

Abstract Academic oncology now recognizes that a cancer's genetic signature may be as important in clinical decision-making as its tissue of origin. However, the degree to which this revolution in thinking has penetrated the clinic is unknown. Our commercial platform, which operates at the point of contact between patients and their physicians, is ideally positioned to address this question. After clinical samples provided by oncologists are analyzed by any molecular diagnostic platform, our internal experts interpret the results using our knowledge integration platform and provide treatment-strategy roadmaps to guide future interventions. Since 2008, approximately 4000 patients have been assessed using this methodology. Overall, the practical utility of the platform has been high: over 70% of cases across all cancer types have revealed actionable results, defined as a molecular profile that suggests either rational on- or off-label use of an FDA-approved agent or enrollment into a clinical trial. Among the 130 patients for whom follow-up is available, use of this platform has resulted in a known effect on therapy selection in 35% of cases and a potential future effect on therapy in an additional 61% of cases. The utility of the approach has also been demonstrated through acceptance by oncologists; 36% of patients who have engaged the service were referred by their oncologists. Although not rising to the rigor of prospective randomized trial data, information in our database may be used in hypothesis generation. For example, while ERBB2 amplification is common in breast cancer, ERBB2 mutations have been documented in a small percentage of non-small cell lung cancer (NSCLC), and were detected in 4% (19/450) of NSCLC cases in our dataset. Mutations or copy number alterations in ERBB2 have also been identified in our dataset in 4% (7/195) of colorectal cancers, 6% (4/68) of urothelial carcinomas, and 10% (4/39) of endometrial carcinomas. In one case, a 61-year-old woman with Stage IV NSCLC presented with a secondary metastasis on the pleura, undergoing treatment with carboplatin and pemetrexed chemotherapy, following earlier treatment of a primary lung tumor with surgery and radiation. Multiplex sequencing identified a somatic exon 20 insertion (AYVM 771-774) in ERBB2, and subsequent treatment with trastuzumab resulted in nearly two years of progression-free survival. These results are consistent with published case studies in this patient population and suggest that clinical trials examining trastuzumab in NSCLC patients with ERBB2 exon 20 mutations may be warranted. In conclusion, our data demonstrate the increasing importance of targeted therapy in clinical oncology. They also demonstrate how databases such as ours, which document uncommon targetable molecular alterations, may have significant impact on real-time treatment decision-making and have potential as hypothesis-generating resources for future clinical trials. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B200. Citation Format: Sheryl K. Elkin, Linda Call, Jo-Ellen Murphy, Kelly Sullivan, Jennifer Carter. A new resource enabling the practical utility of targeted therapy in oncology clinics. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B200.