Vol. 70 No. 5 (2024), REVIEWS

Vol. 70 No. 5 (2024)

New Agents and Approaches for the Treatment of Patients with Metastatic Gastrointestinal Stromal Tumors

REVIEWS

https://doi.org/10.37469/0507-3758-2024-70-5-843-853

Published 30.11.2024

Daria Aleksandrovna Filonenko⁺⁻
Lyudmila Grigorievna Zhukova⁺⁻

Daria Aleksandrovna Filonenko

1SBIH Moscow Clinical Scientific and Practical Center named after A.S.Loginov of DHM Moscow

https://orcid.org/0000-0002-7224-3111

Lyudmila Grigorievna Zhukova

1SBIH Moscow Clinical Scientific and Practical Center named after A.S.Loginov of DHM Moscow

https://orcid.org/0000-0003-4848-6938

##article.numberofdownloads## 62

##article.numberofviews## 164

pdf (Русский)

Keywords

gastrointestinal stromal tumors
GISTs
bezuclastinib
IDRX-42
NM-003
ripretinib
olverembatinib

How to Cite

Filonenko, D. A., & Zhukova, L. G. (2024). New Agents and Approaches for the Treatment of Patients with Metastatic Gastrointestinal Stromal Tumors. Voprosy Onkologii, 70(5), 843–853. https://doi.org/10.37469/0507-3758-2024-70-5-843-853

Abstract

Activating mutations in the KIT and PDGFRA genes are the primary drivers of gastrointestinal stromal tumors (GISTs). Imatinib is extremely effective, but resistance to therapy develops due to secondary mutations. Tyrosine kinase inhibitors (TKIs) used after progression on imatinib have low efficacy. Therefore, new molecules with high antitumor activity in GISTs with secondary mutations are being investigated. Our article is dedicated to new agents that are being actively studied in GIST.

https://doi.org/10.37469/0507-3758-2024-70-5-843-853

##article.numberofdownloads## 62

##article.numberofviews## 164

pdf (Русский)

References

Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. Meta-Analysis J Clin Oncol. 2010; 28(7): 1247-53.-DOI: https://doi.org/10.1200/JCO.2009.24.2099.

Blanke C.D., Demetri G.D., 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): 620-5.-DOI: https://doi.org/10.1200/jco.2007.13.4403.

Verweij J., Casali P.G., Zalcberg J., et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004; 364(9440): 1127-34.-DOI: https://doi.org/10.1016/S0140-6736(04)17098-0.

Demetri G.D., van Oosterom A.T., Garrett C.R., 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.-DOI: https://doi.org/10.1016/S0140-6736(06) 69446-4.

Demetri G.D., Reichardt P., Kang Y.-K., et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013; 381 (9863): 295-302.-DOI: https://doi.org/10.1016/S0140-6736(12)61857-1.

Blay J.-Y., Serrano C., Heinrich M.C., et al. Ripretinib in patients with advanced gastrointestinal stromal tumors (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020; 21(7): 923-934.-DOI: https://doi.org/10.1016/S1470-2045(20) 30168-6.

Heinrich M.C., Maki R.G., Corless C.L., et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. JCO. 2008; 26(33): 5352-5359.-DOI: https://doi.org/10.1200/JCO.2007.15.7461.

Serrano C., Mariño-Enríquez A., Tao D.L., et al. Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumors. Br J Cancer. 2019; 120(6): 612-620.-DOI: https://doi.org/10.1038/s41416-019-0389-6.

Corless C.L., Barnett C.M., Heinrich M.C. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 2011; 11(12): 865-78.-DOI: https://doi.org/10.1038/nrc3143.

Belinsky M.G., Rink L., von Mehren M. Succinate dehydrogenase deficiency in pediatric and adult gastrointestinal stromal tumors. Front Oncol. 2013; 3: 117.-DOI: https://doi.org/10.3389/fonc.2013.00117.

Филоненко Д.А., Тихомирова Т.Е., Мещеряков А.А. Рипретиниб (DCC-2618): новый тирозинкиназный ингибитор для лечения метастатических гастроинтестинальных стромальных опухолей. Российский онкологический журнал. 2020; 25 (1): 4-8.-DOI: https://doi.org/10.18821/1028-9984-2020-25-1-4-8. [Filonenko D.A, Tikhomirova T.E., Meshcheryakov A.A. Ripretinib (DCC-2618): a new tyrosine kinase inhibitor for the treatment of metastatic gastrointestinal stromal tumors. Russian Journal of Oncology. 2020; 25(1): 4-8.-DOI: https://doi.org/10.18821/1028-9984-2020-25-1-4-8. (In Rus)].

Janku F., Abdul Razak A.R., 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.-DOI: https://doi.org/10.1200/JCO.20.00522.

Bauer S., Jones R.L., Blay J.-Y., 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.-DOI: https://doi.org/10.1200/JCO.22.00294.

Bauer S., Jones R.L., 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. JCO. 2023; 41(36_suppl): 397784-397784.-DOI: https://doi.org/10.1200/JCO.2023.41. 36_suppl.397784.

George S., Blay J.Y., Chi P., et al. INSIGHT: A phase 3, randomized, multicenter, open-label study of ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib harboring KIT exon 11 + 17 and/or 18 mutations. JCO. 2023; 41(16_suppl): TPS11582–TPS11582.-DOI: https://doi.org/10.1200/jco.2023.41.16_suppl.tps11582.

Gastrointestinal stromal tumors. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).Version 1.2024. 2024. Continue NCCN.org.-URL: https://www.nccn.org/guidelines/category_1.

George S., Demetri G.D., Lydon N., et al. Phase 1/1b first-in-human study of IDRX-42, a novel oral tyrosine kinase inhibitor (TKI), in patients with metastatic and/or unresectable gastrointestinal stromal tumors (GISTs). J Clin Oncol. 2023; 41(4_suppl): TPS483-TPS483.-DOI: https://doi.org/10.1200/jco.2023.41.4_suppl.tps483.

Schöffski P., Heinrich M.C., Trent J.C., et al. StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX-42 in patients with metastatic gastrointestinal stromal tumors resistant to prior treatment with tyrosine kinase inhibitors (TKIs). J Clin Oncol. 2024; 42(16_suppl): 11501-11501.-DOI: https://doi.org/10.1200/jco.2024.42.16_suppl.11501.

Blum A., Dorsch D., Linde N., et al. Identification of M4205─A highly selective inhibitor of KIT mutations for treatment of unresectable metastatic or recurrent gastrointestinal stromal tumors. J Med Chem. 2023; 66(4): 2386-2395.-DOI: https://doi.org/10.1021/acs.jmedchem.2c00851.

De Sutter L., Wozniak A., Verreet J., et al. Antitumor efficacy of the novel KIT inhibitor IDRX-42 (formerly M4205) in patient- and cell line–derived xenograft models of gastrointestinal stromal tumor (GIST). Clin Cancer Res. 2023; 29(15): 2859-2868.-DOI: https://doi.org/10.1158/1078-0432.CCR-22-3822.

Banks E., Grondine M., Bhavsar D., et al. Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors. Sci Transl Med. 2020; 12(541): eaaz2481.-DOI: https://doi.org/10.1126/scitranslmed.aaz2481.

Филоненко Д.А., Медведева Б.М., Мещеряков А.А. Авапритиниб: новый тирозинкиназный ингибитор для лечения метастатических гастроинтестинальных стромальных опухолей. Современная онкология. 2020; 22 (4): 96-100.-DOI: https://doi.org/10.26442/18151434.2020.4.200409. [Filonenko D.A., Medvedeva B.M., Meshcheryakov A.A. Avapritinib: a new tyrosine kinase inhibitor for treatment of advanced gastrointestinal stromal tumors. The literature review and clinical case. Journal of Modern Oncology. 2021; 22(4): 96-100.-DOI: https://doi.org/10.26442/18151434.2020.4.200409. (In Rus)].

Jones R.L., Serrano C., von Mehren M., 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.-DOI: https://doi.org/10.1016/j.ejca. 2020.12.008.

Serrano C., Leal A., Kuang Y., et al. Phase I study of rapid alternation of sunitinib and regorafenib for the treatment of tyrosine kinase inhibitor refractory gastrointestinal stromal tumors. Clin Cancer Res. 2019; 25(24): 7287-7293.-DOI: https://doi.org/10.1158/1078-0432.CCR-19-2150 52.

Yip D., Zalcberg J.R., Blay J.-Y., et al. ALT-GIST: randomized phase II trial of imatinib alternating with regorafenib versus imatinib alone for the first-line treatment of metastatic gastrointestinal stromal tumor (GIST). JCO. 2019; 37(15_suppl): 11023-11023.-DOI: https://doi.org/10.1200/ JCO.2019.37.15_suppl.11023.

Gebreyohannes Y.K., Burton E.A., Wozniak A., et al. PLX9486 shows anti-tumor efficacy in patient-derived, tyrosine kinase inhibitor-resistant KIT-mutant xenograft models of gastrointestinal stromal tumors. Clin Exp Med. 2019; 19(2): 201-210.-DOI: https://doi.org/10.1007/ s10238-018-0541-2.

Wagner A.J., Severson P.L., Shields A.F., et al. Association of combination of conformation-specific KIT inhibitors with clinical benefit in patients with refractory gastrointestinal stromal tumors: a phase 1b/2a nonrandomized clinical trial. JAMA Oncol. 2021; 7(9): 1343.-DOI: https://doi.org/10.1001/jamaoncol.2021.2086.

Tap W.D., Wagner A.J., Bauer S., et al. Safety, pharmacokinetics (PK), and clinical activity of bezuclastinib + sunitinib in previously-treated gastrointestinal stromal tumor (GIST): results from part 1 of the phase 3 peak study. JCO. 2023; 41(16_suppl): 11537-11537.-DOI: https://doi.org/10.1200/JCO.2023.41.16_suppl.11537.

Wagner A.J., Trent J.C., Attia S., et al. Peak part 1 summary: A phase 3, randomized, open-label multicenter clinical study of bezuclastinib (CGT9486) and sunitinib combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST). J Clin Oncol. 2024; 42(16_suppl): 11533-11533.-DOI: https://doi.org/10.1200/jco.2024.42.16_suppl.11533.

Heinrich M.C., Somaiah N., Trent J.C., et al. Peak study: A phase 3, randomized, open-label multicenter clinical study of bezuclastinib (CGT9486) and sunitinib in combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST). J Clin Oncol. 2024; 42(3_suppl): TPS766-TPS766.-DOI: https://doi.org/10.1200/jco.2024.42.3_suppl.tps766.

Boikos S.A., Pappo A.S., Killian J.K., et al. Molecular Subtypes ofKIT/PDGFRAWild-Type Gastrointestinal Stromal Tumors. JAMA Oncol. 2016; 2(7): 922.-DOI: https://doi.org/10.1001/jamaoncol.2016.0256.

Heinrich M.C., Owzar K., Corless C.L., et al. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol. 2008; 26(33): 5360-7.-DOI: https://doi.org/10.1200/JCO.2008.17.4284.

Janeway K.A., Albritton K.H., Van Den Abbeele A.D., et al. Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib. Pediatr Blood Cancer. 2009; 52(7): 767-71.-DOI: https://doi.org/10.1002/pbc.21909.

Филоненко Д.А., Мещеряков А.А., Архири П.П., et al. SDH-deficient-гастроинтестинальные стромальные опухоли: парадоксальный эффект иматиниба. Современная онкология. 2020; 22 (2): 133-136.-DOI: https://doi.org/10.26442/18151434.2020.2.200053. [Filonenko D.A., Meshcheryakov A.A., Arkhiri P.P., et al. SDH-deficient gastrointestinal stromal tumors: paradoxical effect of imatinib. Journal of Modern Oncology. 2020; 22(2): 133-6.-DOI: https://doi.org/10.26442/18151434.2020.2.200053. (In Rus)].

Qiu H., Zhou Z., Zhou Y., et al. Promising antitumor activity of olverembatinib (HQP1351) in patients (pts) with tyrosine kinase inhibitor- (TKI-) resistant succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST). J Clin Oncol. 2022; 40(16_suppl): 11513-11513.-DOI: https://doi.org/10.1200/jco.2022.40.16_suppl.11513.

Qiu H., Zhou Z.W., Zhou Y., et al. Antitumor activity of olverembatinib (HQP1351) in patients (pts) with tyrosine kinase inhibitor (TKI)–resistant succinate dehydrogenase (SDH)–deficient gastrointestinal stromal tumor (GIST). J Clin Oncol. 2023; 41(16_suppl): 11540-11540.-DOI: https://doi.org/10.1200/jco.2023.41.16_suppl.11540.

Qiu H., Zhou Z.W., Zhou Y., et al. Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and paraganglioma. J Clin Oncol. 2024; 42(16_suppl): 11502-11502.-DOI: https://doi.org/10.1200/jco.2024.42.16_suppl.11502.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Most read articles by the same author(s)

Daria Aleksandrovna Filonenko , Aleksandra Vladimirovna Belogurova , Aleksandr Valerevich Sultanbaev, Konstantin Viktorovich Menshikov , Shamil Ismagilovich Musin , Ilya Anatolevich Fokin , Lyudmila Grigorevna Zhukova , The efficacy of alpelisib in luminal HER2-negative breast cancer with brain metastases: clinical cases. , Voprosy onkologii: Vol. 69 No. 1 (2023)