In recent years, molecular interrogation of tumors and deployment of matched individualized precision therapies has shown remarkable responses in a variety of refractory malignancies. However, to date, few prospective studies have evaluated comprehensive next-generation sequencing (NGS) testing for actionable genomic alterations to guide matched therapy in advanced refractory solid tumors with extensively poor performance status.
The study was a prospective, observational mono-institutional study. The main eligibility criteria were that patients diagnosed with treatment-refractory disease with poor performance status (ECOG PS ≥ 3) undergoing commercial NGS (Foundation Medicine) testing with the intent of clinical application of available matched targeted agents. Variants were classified in three levels of actionability using a novel scale tool. Treatment recommendations were discussed in a molecular tumor board. Among these treated patients, the primary end point for the analysis was the ORR. Secondary end points included DCR, PFS, OS and safety. The registry is ongoing.
From October 2018 to April 2019, 48 patients were enrolled, which concluded ovarian cancer, stomach cancer, liver cancer, and so on, all underwent NGS of a metastatic site biopsy. About 93.8 percent of patients underwent successful molecular analysis (93.8%) and treatment recommendations were given to 28 patients (62.2 %). These included single-agent targeted therapies (60.7%), checkpoint inhibitors (25%), and combination targeted therapies (14.3%). Treatment recommendations were implemented in 22 of 28 patients (78.6%), of whom 8 (36.4%) showed complete remission (n = 1) or partial response (n = 7), in addition, 16 patients (72.7%) receiving off-label treatments.
Genomic-guided individualized precision therapy is effective for a small proportion of patients in challenging clinical situations. Molecular tumor board and evidenced based actionable gene variation scale tool are effective approach to improve the effectiveness of genomic-guided precision therapy.
Institutional review board of the Second Hospital of Tianjin Medical University.
Has not received any funding.
The author has declared no conflicts of interest.