Ripretynib w leczeniu chorych z zaawansowanymi nowotworami podścieliskowymi przewodu pokarmowego (GIST)
Streszczenie
Nowotwory podścieliskowe przewodu pokarmowego (GIST, gastrointestinal stromal tumor) występują stosunkowo rzadko (0,4 do 2 przypadków na 100 000 rocznie) i stanowią około 1–2% nowotworów przewodu pokarmowego. Zgodnie z najnowszą klasyfikacją mięsaków opracowaną przez Światową Organizację Zdrowia (WHO, World Health Organization) w 2020 roku wszystkie GIST określa się jako nowotwory złośliwe, niezależnie od wielkości lub indeksu mitotycznego. W leczeniu systemowym GIST stosuje się inhibitory receptora kinazy tyrozynowej KIT i receptora płytkopochodnego czynnika wzrostu (PDGFRA, platelet-derived growth factor receptor), takie jak imatynib, sunitynib lub regorafenib. Skuteczność imatynibu jest znacznie mniejsza w przypadku mutacji wtórnych w genie KIT. Najnowszy lek z grupy inhibitorów KIT — ripretynib — jako pierwszy wykazał skuteczność w przypadku większości mutacji związanych z opornością, a także GIST typu dzikiego, w którym nie stwierdzono mutacji KIT i PDGFRA. Analiza wyników badania INVICTUS wykazała korzystny wpływ ripretynibu w zalecanej dawce 150 mg/dobę na czas przeżycia wolnego od progresji choroby (PFS, progression-free survival) u chorych z zaawansowanym lub przerzutowym GIST leczonych wcześniej co najmniej trzema innymi inhibitorami. Wstępne wyniki badania klinicznego III fazy INTRIGUE nie wykazały jednak poprawy PFS u chorych na GIST otrzymujących ripretynib w terapii drugiej linii w porównaniu z sunitynibem. Ripretynib wykazuje korzystny i akceptowalny profil bezpieczeństwa i jest zalecany w leczeniu chorych z zaawansowanym GIST w czwartej linii leczenia. W przedstawionej publikacji podsumowano najważniejsze dane dotyczące skuteczności i bezpieczeństwa ripretynibu w leczeniu chorych na GIST oraz zalecenia dotyczące jego stosowania.
Słowa kluczowe: GISTKITPDGFRAripretynibinhibitor kinazy tyrozynowej
Referencje
- Kelly CM, Gutierrez Sainz L, Chi P. The management of metastatic GIST: current standard and investigational therapeutics. J Hematol Oncol. 2021; 14(1): 2.
- Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 2011; 11(12): 865–878.
- Cassier PA, Ducimetière F, Lurkin A, et al. A prospective epidemiological study of new incident GISTs during two consecutive years in Rhône Alpes region: incidence and molecular distribution of GIST in a European region. Br J Cancer. 2010; 103(2): 165–170.
- Søreide K, Sandvik OM, Søreide JA, et al. Global epidemiology of gastrointestinal stromal tumours (GIST): A systematic review of population-based cohort studies. Cancer Epidemiol. 2016; 40: 39–46.
- Casali PG, Blay JY, Abecassis N, et al. Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2022; 33(1): 20–33.
- Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006; 130(10): 1466–1478.
- Blay JY, Kang YK, Nishida T, et al. Gastrointestinal stromal tumours. Nat Rev Dis Primers. 2021; 7(1): 22.
- Nishida T, Blay JY, Hirota S, et al. The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines. Gastric Cancer. 2016; 19(1): 3–14.
- Fletcher CDM, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Int J Surg Pathol. 2002; 10(2): 81–89.
- Hanks SK, Quinn AM, Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988; 241(4861): 42–52.
- Rutkowski P, Koseła-Paterczyk H, Kozak K, et al. Postępowanie diagnostyczno-terapeutyczne u chorych na mięsaki tkanek miękkich u dorosłych — zalecenia ekspertów. Onkol Prakt Klin Edu. 2023; 9(3): 149–180.
- Klug LR, Khosroyani HM, Kent JD, et al. New treatment strategies for advanced-stage gastrointestinal stromal tumours. Nat Rev Clin Oncol. 2022; 19(5): 328–341.
- Singer S, Rubin BP, Lux ML, et al. Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol. 2002; 20(18): 3898–3905.
- Roberts KG, Odell AF, Byrnes EM, et al. Resistance to c-KIT kinase inhibitors conferred by V654A mutation. Mol Cancer Ther. 2007; 6(3): 1159–1166.
- Mol CD, Dougan DR, Schneider TR, et al. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem. 2004; 279(30): 31655–31663.
- Kang DY, Park CK, Choi JS, et al. Multiple gastrointestinal stromal tumors: Clinicopathologic and genetic analysis of 12 patients. Am J Surg Pathol. 2007; 31(2): 224–232.
- Duensing A, Medeiros F, McConarty B, et al. Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene. 2004; 23(22): 3999–4006.
- Debiec-Rychter M, Sciot R, Le Cesne A, et al. EORTC Soft Tissue and Bone Sarcoma Group, Italian Sarcoma Group, Australasian GastroIntestinal Trials Group. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006; 42(8): 1093–1103.
- Vanden Bempt I, Vander Borght S, Sciot R, et al. Comprehensive targeted next-generation sequencing approach in the molecular diagnosis of gastrointestinal stromal tumor. Genes Chromosomes Cancer. 2021; 60(4): 239–249.
- Burch J, Ahmad I. Gastrointestinal Stromal Cancer. In: StatPearls 2022. StatPearls Publishing LLC, Treasure Island (FL) 2022.
- Rutkowski P, Gronchi A, Hohenberger P, et al. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors (GIST): the EORTC STBSG experience. Ann Surg Oncol. 2013; 20(9): 2937–2943.
- Joensuu H, Eriksson M, Sundby Hall K, et al. Adjuvant Imatinib for High-Risk GI Stromal Tumor: Analysis of a Randomized Trial. J Clin Oncol. 2016; 34(3): 244–250.
- Joensuu H, Eriksson M, Sundby Hall K, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012; 307(12): 1265–1272.
- Joensuu H, Wardelmann E, Sihto H, et al. Effect of KIT and PDGFRA Mutations on Survival in Patients With Gastrointestinal Stromal Tumors Treated With Adjuvant Imatinib: An Exploratory Analysis of a Randomized Clinical Trial. JAMA Oncol. 2017; 3(5): 602–609.
- Blanke CD, Demetri GD, von Mehren M, et al. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008; 26(4): 620–625.
- Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002; 347(7): 472–480.
- Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol. 2010; 28(7): 1247–1253.
- Demetri GD, Reichardt P, Kang YK, et al. GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013; 381(9863): 295–302.
- Mazzocca A, Napolitano A, Silletta M, et al. New frontiers in the medical management of gastrointestinal stromal tumours. Ther Adv Med Oncol. 2019; 11: 1758835919841946.
- Heinrich MC, Jones RL, von Mehren M, et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020; 21(7): 935–946.
- Jones R, Serrano C, Mehren Mv, et al. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021; 145: 132–142.
- Grunewald S, Klug LR, Mühlenberg T, et al. Resistance to Avapritinib in PDGFRA-Driven GIST Is Caused by Secondary Mutations in the PDGFRA Kinase Domain. Cancer Discov. 2021; 11(1): 108–125.
- Blay JY, Serrano C, Heinrich MC, et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020; 21(7): 923–934.
- Dhillon S. Ripretinib: First Approval. Drugs. 2020; 80(11): 1133–1138.
- Smith BD, Kaufman MD, Lu WP, et al. Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. Cancer Cell. 2019; 35(5): 738–751.e9.
- Mohammadi M, Gelderblom H. Systemic therapy of advanced/metastatic gastrointestinal stromal tumors: an update on progress beyond imatinib, sunitinib, and regorafenib. Expert Opin Investig Drugs. 2021; 30(2): 143–152.
- DiNitto JP, Deshmukh GD, Zhang Y, et al. Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance. J Biochem. 2010; 147(4): 601–609.
- Lostes-Bardaji MJ, García-Illescas D, Valverde C, et al. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward. Ther Adv Med Oncol. 2021; 13: 1758835920986498.
- Pilco-Janeta DF, García-Valverde A, Gomez-Peregrina D, et al. Emerging drugs for the treatment of gastrointestinal stromal tumors. Expert Opin Emerg Drugs. 2021; 26(1): 53–62.
- Arock M, Sotlar K, Akin C, et al. KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis. Leukemia. 2015; 29(6): 1223–1232.
- EMA. Quinlock Charakterystyka Produktu Leczniczego.
- Pharmaceuticals., D., QINLOCK™ (ripretinib) tablets: US prescribing information 2020.
- Ripretinib, in Drugs and Lactation Database (LactMed). 2006, National Library of Medicine (US): Bethesda (MD).
- Janku F, Abdul Razak AR, Chi P, et al. Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib. J Clin Oncol. 2020; 38(28): 3294–3303.
- Mehren Mv, Heinrich MC, George S, et al. 1540P Ripretinib as ≥4th-line treatment in patients with advanced gastrointestinal stromal tumor: Long-term update from the phase III INVICTUS study. Annals of Oncology. 2021; 32: S1120–S1121.
- Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006; 368(9544): 1329–1338.
- Serrano C, Heinrich M, George S, et al. O-13 Efficacy and safety of ripretinib as ≥4th-line therapy for patients with gastrointestinal stromal tumor following crossover from placebo: Analyses from INVICTUS. Ann Oncol. 2020; 31: 236.
- Heinrich M, George S, Zalcberg J, et al. Quality of life (QoL) and self-reported function with ripretinib in ≥4th-line therapy for patients with gastrointestinal stromal tumors (GIST): Analyses from INVICTUS. J Clin Oncol. 2020; 38(15_suppl): 11535–11535.
- Schöffski P, George S, Heinrich MC, et al. Patient-reported outcomes in individuals with advanced gastrointestinal stromal tumor treated with ripretinib in the fourth-line setting: analysis from the phase 3 INVICTUS trial. BMC Cancer. 2022; 22(1): 1302.
- Załącznik do Raportu oceny technologii o wysokiej innowacyjności w ramach Funduszu Medycznego za rok 2022, nr 18: Qinlock (ripretynib) we wskazaniu: w leczeniu dorosłych pacjentów z zaawansowanym nowotworem podścieliskowym przewodu pokarmowego (GIST), którzy byli wcześniej leczeni trzema lub więcej inhibitorami kinazy, w tym imatynibem. Opracowanie analityczne 18.02.2022.
- Bauer S, Jones RL, Blay JY, et al. Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022; 40(34): 3918–3928.
- Heinrich M, Jones R, Gelderblom H, et al. INTRIGUE: A phase III, randomized, open-label study to evaluate the efficacy and safety of ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib. J Clin Oncol. 2022; 40(36_suppl): 359881–359881.
- Bauer S, Jones R, George S, et al. Mutational heterogeneity of imatinib resistance and efficacy of ripretinib vs sunitinib in patients with gastrointestinal stromal tumor: ctDNA analysis from INTRIGUE. J Clin Oncol. 2023; 41(36_suppl): 397784–397784.
- Raut CP, Espat NJ, Maki RG, et al. Efficacy and Tolerability of 5-Year Adjuvant Imatinib Treatment for Patients With Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor: The PERSIST-5 Clinical Trial. JAMA Oncol. 2018; 4(12): e184060.
- Dematteo RP, Ballman KV, Antonescu CR, et al. American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009; 373(9669): 1097–1104.
- Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004; 364(9440): 1127–1134.
- Demetri GD, Garrett CR, Schöffski P, et al. Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure. Clin Cancer Res. 2012; 18(11): 3170–3179.
- Zalcberg JR. Ripretinib for the treatment of advanced gastrointestinal stromal tumor. Therap Adv Gastroenterol. 2021; 14: 17562848211008177.
- Lin LC, Huang WK, Yen CC, et al. Compassionate Use of Ripretinib for Patients With Metastatic Gastrointestinal Stromal Tumors: Taiwan and Hong Kong Experience. Front Oncol. 2022; 12: 883399.
- Li J, Cai S, Zhou Y, et al. Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors as a Fourth- or Later-Line Therapy: A Multicenter, Single-Arm, Open-Label Phase II Study. Clin Cancer Res. 2022; 28(16): 3425–3432.
- Napolitano A, Lim SY, Lopez LFF, et al. 80P Expanded access program use of ripretinib in advanced GIST patients in the United Kingdom. ESMO Open. 2023; 8(1): 101117.
- von Mehren M, Kane JM, Riedel RF, et al. NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022. J Natl Compr Canc Netw. 2022; 20(11): 1204–1214.
- Zalcberg JR, Heinrich MC, George S, et al. Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study. Oncologist. 2021; 26(11): e2053–e2060.