Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China.

AIM: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. METHODS: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). RESULTS: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). CONCLUSIONS: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.

Existence of memory in membrane channels: analysis of ion current through a voltage-dependent potassium single channel.

Ion current fluctuation of voltage-dependent potassium channel in LßT2 cells has been investigated by autocorrelation function and DFA (detrended fluctuation analysis) methods. The calculation of the autocorrelation function exponent and DFA exponent of the sample was based on the digital signals or the 0-1 series corresponding to closing and opening of channels after routine evolution, rather than the sequence of sojourn times. The persistent character of the correlation of the time series was evident from the slow decay of the autocorrelation function. DFA exponent α was significantly greater than 0.5. The main outcome has been the demonstration of the existence of memory in this ion channel. Thus, the ion channel current fluctuation provided information about the kinetics of the channel protein. The result suggests the correlation character of the ion channel protein non-linear kinetics indicates whether the channel is open or not.