Final clinical outcomes of nationwide precision oncology pilot study; KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS) KCSG AL-20-05

초록

Background Next generation sequencing (NGS) has become widely available but molecular profiling guided therapy (MGT) has not been established in the real world due to a lack of available therapies and expertise to interpret and match treatment in Korea. Methods Patients with advanced solid tumors without remaining standard treatment were enrolled. Virtual, central molecular tumor boards (cMTB) reviewed patients’ NGS reports and recommended clinical trials or investigational medicinal products (IMPs) as previously described (https://doi.org/10.1016/j.esmoop.2022.100653). Primary variable was to assess the proportion of patients with actionable genomic alterations and patients receiving MGT as MTB recommendations. Other variables were duration of treatment (DoT), overall response rate (ORR), disease control rate (DCR) and safety. Results From Feb 2021 to Feb 2022, 198 patients were enrolled. Median time from case submission to MTB discussion was 7 days (range, 2-20) and concordance rate between pre-MTB physicians’ choice and MTB recommendations were 60.1% (119/198). A total of 107 (54.0%) received IMPs based on MTB decision (32, TE; 21, AZ; 14, TP; 13, BE; 8, AP; 6, CA; 5, DT; 4, AL; 3, EL; 1, BV). ORR and DCR were 13.3% (1 CR, 9 PR, 45 SD, and 20 PD), and 73.3%. DoT was 3.6 months (95% CI, 2.8-5.0) and 4 months DoT rate (4MDoTR) was 45.5%. DoT>12 months were observed in 10 (9.3%). TE showed a durable DoT, regardless of ERBB2 amplification and mutation (5.8 and 4.0 months), previous exposure of anti-HER2 targeted agents (4.0(No) vs. 5.4 months (Yes)), and high (6>) vs. low (6<) copy number variation (4.0 and 8.0 months). Conclusions KOSMOS suggested the feasibility of nationwide cMTB guided MGT and also showed modest ORR, and a promising DCR in heavily pre-treated patients. KOSMOS-II (NCT05525858) is currently underway to confirm this in larger number of patients.