Rare Tumor Clinic: The University of California San Diego Moores Cancer Center Experience with a Precision Therapy Approach

Background. Patients with rare tumors may lack approved treatments and clinical trial access. Although each rare tumor is uncommon, cumulatively they account for approximately 25% of cancers. We recently initiated a Rare Tumor Clinic that emphasized a precisionmedicine strategy. Materials and Methods. We investigated the first 40 patients presenting at the Rare Tumor Clinic. Next-generation sequencing (NGS) of tissue and plasma-derived, circulating-tumor DNA (ctDNA), and proteinmarkers were assessed. Results. Median age was 58 years (range, 31-78 years); 70% (28/ 40) were women; median number of previous systemic therapies was 2 (range 0-7). The most common diagnoses were sarcoma (n = 7) for solid tumors and Erdheim-Chester disease (n = 5) for hematologic malignancies. Twenty distinct diagnoses were seen. Examples of ultrarare tumors included ameloblastoma, yolk sac liver tumor, ampullary cancer, and Castleman's disease. Altogether, 32 of 33 patients (97%) with tissue NGS and 15 of 33 (45%) with ctDNA sequencing harbored >= 1 alteration. Overall, 92.5% of patients (37/40) had >1 actionable target based on either genomic (n532) or protein (n = 27) markers. In total, 52.5% (21/40) received matched therapy; 52.4% (11/21) achieved stable disease (SD) >= 6 months (n = 3), partial remission (PR; n56), or complete remission (CR; n = 2). Matched therapy resulted in significantly longer progressionfree survival compared with last prior unmatched therapy (hazard ratio 0.26, 95% confidence interval 0.10-0.71, p = .008). Conclusion. Identifying genomic and protein markers in patients with rare/ultrarare tumors was feasible. When therapies were matched, > 50% of patients attained SD >= 6 months, PR, or CR. Further precision medicine clinical investigations focusing on rare and ultrarare tumors are urgently needed.