Rare tumor clinic: The UCSD Moores Cancer Center experience with a precision therapy approach.

Abstract

11578 Background: Rare tumors have an incidence of < 15/100,000 per year; utra-rare, prevalence < 2000 in the USA. Patients (pts) may lack approved treatments and clinical trial access. Although each rare tumor is uncommon, cumulatively they account for > 20% of cancers. We recently initiated a Rare Tumor Clinic that emphasized a precision medicine strategy (genomic and proteomic analysis and individualized therapy). We report our preliminary experience. Methods: We investigated outcome among the first 40 pts presenting to the Rare Tumor Clinic at UC San Diego Moores Center for Personalized Cancer Therapy. Whenever possible, next-generation sequencing (NGS) of tissue and plasma-derived circulating tumor DNA (ctDNA) as well as proteomic markers were assessed. Results: Median age was 58 (range, 31 – 78 yo); 70% (28/40) were women; median number of previous systemic therapies, 2 (range, 0-7). The most common diagnoses were sarcoma (N = 7) for solid tumors; Erdheim-Chester disease (N = 5), for hematologic malignancies. Twenty distinct diagnoses were seen. Examples of ultra-rare tumors included ameloblastoma, yolk sac liver tumor, ampullary cancer, Castleman's disease, and desmoid tumor. 82.5% of pts (33/40) had tissue NGS (182 to 405 genes); 7.5% (3/40), inadequate tissue. The median number of characterized tissue alterations was 3 (range, 0 to 24); 32 pts (80%) had ≥1 characterized genomic alteration. 33 pts (82.5%) had ctDNA analysis; 15 pts had ≥1 characterized alteration. Among those 15 pts, median number of characterized alterations was 3 (range, 1 to 14). 92.5% (37/40) of pts had ≥ 1 actionable target based on either genomic (32 pts) or proteomic markers (27 pts) (FDA-approved [mostly off-label] or investigational agent). 52.5% (21/40) received matched therapy; 52.4% (11/21) achieved SD≥6 months (N = 3)/CR (N = 2)/PR (N = 6). Matched therapy resulted in significantly longer PFS compared to last prior unmatched therapy (HR: 0.26, 95% CI: 0.10 – 0.71 [p = 0.008]). Conclusions: Identifying genomic and proteomic markers in pts with rare and ultra-rare tumors was feasible. When therapies were matched, > 50% of pts attained SD≥6 months/CR/PR. Further clinical investigations focusing on rare and ultra-rare tumors are urgently needed.