Clinical next generation sequencing for precision oncology in rare cancers.

Abstract

2582 Background: Rare tumors receive little financial support or interest from major drug developers or clinical investigators. They are by nature difficult to study even in a large academic medical center. As such, no standard of care exists for many of these cancers and treatment is often extrapolated. ESMO defines rare tumors as 5/100,000 persons per year. We examined patients with rare tumors for potentially targetable genomic alterations using next generation exome sequencing (NGS). Methods: We reviewed charts of patients with rare tumors per the ESMO definition. Sarcomas were excluded. Patients were referred to investigational therapeutics department and underwent CLIA certified comprehensive genomic profiling (Foundation Medicine). Actionable alterations were defined as targeted by a drug available on-label, off-label, or in clinical trials. Results: Among the 95 patients analyzed median age was 51 years (range 2-75). M:F ratio 46:49. Overall, there were 47 different subtypes in our dataset with the most common being adenoid cystic (13%), cholangiocarcinoma (7%), metaplastic breast (6%), gallbladder (5%), and carcinoid (4%). Eighty-seven out of 96 patients (92%) had at least one genomic alteration identified with mean of 2.6 mutations per patient. Of the patients with identifiable mutations, the most common were TP53 (23%), KRAS (10%), PIK3CA (9%), CDKN2A/B (8%), BRAF (7%), MLL (7%), and ARID1A (6%). Thirty-six patients (38%) had at least one potentially actionable alteration in 21 different tumors (eg: PI3K in metaplastic breast and adenoid cystic carcinomas and BRAFV600Ein Erdheim-Chester disease). Nine patients received targeted therapy. Of these 9 patients, 3 had PR, 4 had SD, and 2 had PD as best response (table). Conclusions: The addition of CGP to management of rare tumors adds a potential line of therapy especially in RAF pathway altered ultra-rare cancers that have no standard of care. [Table: see text]