Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study.

BACKGROUND: Avapritinib is a type 1 kinase inhibitor designed to potently and selectively inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation. This multicenter, single-arm, open-label, phase I/II bridging study of NAVIGATOR in Chinese patients evaluated the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST). METHODS: Phase I comprised dose escalation for safety and phase II dose determination. Phase II comprised dose expansion for safety/efficacy evaluations in patients with PDGFRA D842V mutations or patients having received at least 3 lines of therapy without PDGFRA D842V mutations. The primary endpoints were recommended phase II dose, safety, and Independent Radiology Review Committee (IRRC)-assessed objective response rate (ORR). RESULTS: No dose-limiting toxicities occurred (n = 10); the recommended phase II dose was avapritinib 300 mg once daily orally. Fifty-nine patients initially received avapritinib 300 mg. Common grade ≥3 treatment-related adverse events were anemia, decreased white blood cell count, increased blood bilirubin levels, and decreased neutrophil count. In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or later-line setting were 22% and 35%, respectively. Median progression-free survivals were 5.6 months for both. Overall survival data were immature and not calculated. CONCLUSION: Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy (ClinicalTrials.gov Identifier: NCT04254939).

[Serum Levels of Interleukin-17 and Tumor Necrosis Factor-α in Dermatomyositis Patients with Dif- ferent Syndrome Types of Chinese Medicine].

Objective To observe serum levels of interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) in dermatomyositis (DM) patients with different syndrome types of Chinese medicine (CM). Methods Totally 68 dermatomyositis patients were recruited and grouped by syndrome typing of CM, i.e., heat-toxin flourishing syndrome (20 cases) , damp-heat accumulation syndrome (14 cases) , cold-dampness obstruction syndrome (12 cases) , Pi-Shen deficiency syndrome (12 cases) , Gan-Shen yin deficiency syndrome (10 cases). Meanwhile, 64 healthy volunteers were recruited as healthy con- trols. The levels of IL-17 and TNF-α in serum were detected in patient groups and the healthy group. Results Compared with the healthy control group, the serum IL-17 level increased in patients with heat-toxin flourishing syndrome, damp-heat accumulation syndrome, and cold-dampness obstruction syndrome (P <0. 01) ; the serum TNF-α level increased in DM patients with each syndrome (P <0. 01 , P < 0. 05). Compared with the heat-toxin flourishing syndrome group, the serum IL-17 level decreased in patients with cold-dampness obstruction syndrome, Pi-Shen deficiency syndrome, and Gan-Shen yin deficiency syndrome (P <0. 01) ; and the serum TNF-α level decreased in patients with Pi-Shen deficiency syndrome and Gan-Shen yin deficiency syndrome (P <0. 01). Compared with the dampheat accumulation syndrome group, the serum IL-17 level decreased in patients with cold-dampness obstruction syn- drome, Pi-Shen deficiency syndrome, and Gan-Shen yin deficiency syndrome (P <0. 01) , and the serum TNF-α level decreased in patients with Pi-Shen deficiency syndrome and Gan-Shen yin deficiency syndrome (P <0. 01). Compared with the cold-dampness obstruction syndrome group, the serum levels of IL-17 and TNF-α decreased in patients with Pi-Shen deficiency syndrome and Gan-Shen yin deficiency syndrome (P <0. 01 , P <0. 05). Conclusion Serum levels of IL-17 and TNF-α are different in DM patients with different syndrome types of CM.