Cancer Therapy Directed by Comprehensive Genomic Profiling: A Single Center Study
| Autor: | J. Jack Lee, Bettzy Stephen, Vivek Subbiah, Vincent A. Miller, Yali Li, Siqing Fu, Ralph Zinner, Sarina Anne Piha-Paul, Roosevelt Anderson, Apostolia Maria Tsimberidou, Danxia Ke, Jennifer J. Wheler, Razelle Kurzrock, Gerald Steven Falchook, Aung Naing, Daniel D. Karp, Filip Janku, David S. Hong, Roman Yelensky |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Single Center Young Adult 03 medical and health sciences 0302 clinical medicine Breast cancer Neoplasms Internal medicine Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor medicine Humans Molecular Targeted Therapy Prospective Studies Precision Medicine Prospective cohort study Survival rate Aged Neoplasm Staging Aged 80 and over business.industry Gene Expression Profiling Hazard ratio High-Throughput Nucleotide Sequencing Cancer Middle Aged Prognosis medicine.disease Surgery Survival Rate Clinical trial 030104 developmental biology 030220 oncology & carcinogenesis Female Sarcoma business Follow-Up Studies Signal Transduction |
| Zdroj: | Cancer Research. 76:3690-3701 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Innovative molecular diagnostics deployed in the clinic enable new ways to stratify patients into appropriate treatment regimens. These approaches may resolve a major challenge for early-phase clinical trials, which is to recruit patients who, while having failed previous treatments, may nevertheless respond to molecularly targeted drugs. We report the findings of a prospective, single-center study conducted in patients with diverse refractory cancers who underwent comprehensive genomic profiling (CGP; next-generation sequencing, 236 genes). Of the 500 patients enrolled, 188 (37.6%) received either matched (N = 122/188, 65%) or unmatched therapy (N = 66/188, 35%). The most common reasons that patients were not evaluable for treatment included insufficient tissue, death, or hospice transfer. The median number of molecular alterations per patient was five (range, 1–14); median number of prior therapies, four. The most common diagnoses were ovarian cancer (18%), breast cancer (16%), sarcoma (13%), and renal cancer (7%). Of the 339 successfully profiled patients, 317 (93.5%) had at least one potentially actionable alteration. By calculating matching scores, based on the number of drug matches and genomic aberrations per patient, we found that high scores were independently associated with a greater frequency of stable disease ≥6 months/partial/complete remission [22% (high scores) vs. 9% (low scores), P = 0.024], longer time-to-treatment failure [hazard ratio (HR) = 0.52; 95% confidence interval (CI) = 0.36–0.74; P = 0.0003], and survival (HR = 0.65; 95% CI = 0.43–1.0; P = 0.05). Collectively, this study offers a clinical proof of concept for the utility of CGP in assigning therapy to patients with refractory malignancies, especially in those patients with multiple genomic aberrations for whom combination therapies could be implemented. Cancer Res; 76(13); 3690–701. ©2016 AACR. |
| Databáze: | OpenAIRE |
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