Molecular targeted therapies have clinical benefit on patients with specific molecular alterations. We hypothesized that on enrolling patients in phase I clinical trials, a pre-screening system using next generation sequencing (NGS), to identify molecularly “matched” patients, would increase response rate and accelerate drug development.
We prospectively recruited patients with solid tumors candidates for phase I trials at the National Cancer Center Hospital in Japan. Genomic sequencing was performed on archival tissue samples using an original oncogene panel “NCC oncopanel” (90 mutations/amplifications and 10 fusion genes). On the basis of the identified genetic alterations, a multidisciplinary team interpreted the gene profile and selected a suitable ongoing phase I trial. Primary endpoint was proportion of patients registered in phase I trials after the molecular characterization. Secondary endpoint was proportion of patients treated with the “matched” molecular targeted drugs.
From July 2013 to October 2014, 183 patients with breast, gastric, ovarian, lung, and 5 other cancer types were enrolled. Sequencing was performed in 131 (72%) of all patients. An average of 1.93 mutations and 0.29 amplifications per patient were identified. Of 131 patients, 59 (45%) patients had at least one actionable altered gene, and alterations were found most frequently in breast cancer patients. Altered genes included PIK3CA (15 patients), CCND1 (12 patients), BRCA2 (9 patients), and BRCA1 (3 patients). 28 (21%) entered phase I trials, 11 (8.4%) underwent therapy with the “matched” drug. Of the patients treated with the “matched” drug, 3 showed objective response, and 3 had stable disease.
NGS-based molecular pre-screening is a feasible and potent useful platform before registrating patients in a phase I clinical trial.
Clinical trial identification
All authors have declared no conflicts of interest.