Применение панелей комплексного молекулярного профилирования при опухолях желудочно-кишечного тракта. Обзор литературы и собственные результаты

Автор: Кузнецова О.А., Федянин М.Ю., Иванов М.В., Трякин А.А., Борщев Г.Г., Лебедева А.А., Веселовский Е.М., Ледин Е.В., Шамрикова В.А., Степанова М.Л., Шило П.С., Чепорова М.С.

Журнал: Злокачественные опухоли @malignanttumors

Статья в выпуске: 3S1 т.13, 2023 года.

Бесплатный доступ

Введение: Появление в клинической практике возможности комплексного молекулярного профилирование (КМП) и регистрация новых таргетных препаратов привело к развитию прецизионного подхода в онкологии. Задачей работы являлась оценка опыта применения КМП у пациентов с распространенными опухолями желудочно-кишечного тракта (ЖКТ) в Российской Федерации. Материалы и методы: Проведен ретроспективный анализ клинических данных и отчетов КМП пациентов с опухолями ЖКТ. Цель исследования — оценка доли пациентов, которые получают молекулярно-направленную терапию (МНТ) после КМП, а также определение клинической пользы, которая оценивалась как длительность ответа на МНТ ≥ 6 месяцев. Также проведена оценка распределения альтераций по шкале ESCAT в зависимости от нозологии, частота объективных ответов и ОВ при назначении МНТ или стандарта терапии. Результаты: С марта 2018 по июнь 2023 гг. КМП было проведено 147 пациентам с опухолями ЖКТ (КРР — 64 %, РПЖ — 14,3 %, РЖ- 12,2 %, ХЦР — 9,5 %). Средний возраст составил 58 лет, лица мужского и женского пола были представлены в равной степени, среднее число линий до КМП — 2. МНТ проведена 19 (13 %) пациентам, клиническая польза зафиксирована у 6 больных (4 %). Одногодичная ОВ: 47,4 % против 29,5 % в группе МНТ и стандарта терапии (ОР = 2,147, 95 % ДИ 1,075–4,289, p = 0,020). КМП позволило выявить 12,1 % пациентов с максимальным уровнем ESCAT — I, 1,3 % — ESCAT II, 31,5 % — ESCAT III и 16,8 % — ESCAT IV. У 38,2 % пациентов обнаруженные при КМП альтерации не являлись предиктивными. За пределами ESCAT I, II клиническая польза была достигнута лишь у двух пациентов (1,3 %). Выводы: Несмотря на увеличение частоты объективных ответов и выявленные различия в ОВ, проведение доступных вариантов КМП приводит к смене тактики лечения у небольшой доли пациентов. Лишь 4 % пациентов в нашем исследовании получили клиническую пользу от МНТ, что соответствует данным литературы.

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Комплексное молекулярное профилирование, опухоли желудочно-кишечного тракта, прецизионная онкология

Короткий адрес: https://sciup.org/140302070

IDR: 140302070 | DOI: 10.18027/2224-5057-2023-13-3s1-7-17

Список литературы Применение панелей комплексного молекулярного профилирования при опухолях желудочно-кишечного тракта. Обзор литературы и собственные результаты

Moscow JA, Fojo T, Schilsky RL. The evidence framework for precision cancer medicine. Nat Rev Clin Oncol. 2018 ; 15 (3) : 183-192. https://doi.org/10.1038/nrclinonc.2017.186.
Mateo J, Steuten L, Aftimos P, et al. Delivering precision oncology to patients with cancer. Nat Med. 2022 ; 28 (4) : 658-665. https://doi.org/10.1038/s41591-022-01717-2.
Berger MF, Mardis ER. The emerging clinical relevance of genomics in cancer medicine. Nat Rev Clin Oncol. 2018 ; 15 (6) : 353-365. https://doi.org/10.1038/s41571-018-0002-6.
MacConaill LE. Existing and emerging technologies for tumor genomic profiling. J Clin Oncol. 2013 ; 31 (15) : 1815-1824. https://doi.org/10.1200/JCO.2012.46.5948.
Schwaederle M, Zhao M, Lee JJ, et al. Association of Biomarker-Based Treatment Strategies With Response Rates and Progression-Free Survival in Refractory Malignant Neoplasms : A Meta-analysis. JAMA Oncol. 2016 ; 2 (11) : 1452-1459. https://doi.org/10.1001/jamaoncol.2016.2129.
Radovich M, Kiel PJ, Nance SM, et al : Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers. Oncotarget 7 : 56491-56500, 2016 7.
Wheler JJ, Yelensky R, Stephen B, et al : Prospective study comparing outcomes in patients with advanced malignancies on molecular alteration-matched versus non-matched therapy. J Clin Oncol 33, 2015 (suppl 115 ; abstr 11019).
Meador CB, Micheel CM, Levy MA. et al. Beyond histology : Translating tumor genotypes into clinically effective targeted therapies. Clin Cancer Res. 2014 ; 20 : 1-12.
Frampton GM, Fichtenholtz A, Otto GA. et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013 ; 31 : 1023-1031.
Wagle N, Berger MF, Davis MJ. et al. High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov. 2012 ; 2 : 82-93.
Ulahannan D, Kovac MB, Mulholland PJ. et al. Technical and implementation issues in using next-generation sequencing of cancers in clinical practice. Br J Cancer. 2013 ; 109 : 827-835.
Johnson DB, Dahlman KH, Knol. et al. Enabling a genetically informed approach to cancer medicine : a retrospective evaluation of the impact of comprehensive tumor profiling using a targeted next-generation sequencing panel. Oncologist. 2014 Jun ; 19 (6) : 616-22. https://doi.org/10.1634/theoncologist.2014-0011.
Gibbs SN, Peneva D, Cuyun Carter G, et al., Comprehensive Review on the Clinical Impact of Next-Generation Sequencing Tests for the Management of Advanced Cancer. JCO Precis Oncol. 2023 Jun ; 7 : e2200715. https://doi.org/10.1200/PO.22.00715.
Schwaederle, Maria et al. “Impact of Precision Medicine in Diverse Cancers : A Meta-Analysis of Phase II Clinical Trials.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 33,32 (2015) : 3817-25. https://doi.org/10.1200/JCO.2015.61.5997.
Mosele, F et al. “Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers : a report from the ESMO Precision Medicine Working Group.” Annals of oncology : official journal of the European Society for Medical Oncology vol. 31,11 (2020) : 1491-1505. https://doi.org/10.1016/j.annonc.2020.07.014.
Chakravarty, Debyani et al. “Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer : ASCO Provisional Clinical Opinion.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 40,11 (2022) : 1231-1258. https://doi.org/10.1200/JCO.21.02767.
Cobain EF, Wu YM, Vats P, et al. Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors. JAMA Oncol. 2021 Apr 1 ; 7 (4) : 525-533. https://doi.org/10.1001/jamaoncol.2020.7987. PMID: 33630025; PMCID: PMC7907987.
Hilal T, Nakazawa M, Hodskins J, et al., Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy. BMC Cancer. 2017 Aug 30 ; 17 (1) : 602. https://doi.org/10.1186/s12885-017-3587-8. PMID: 28854908; PMCID: PMC5577820.
Tsimberidou AM, Iskander NG, Hong DS, et al. Personalized medicine in a phase I clinical trials program : the MD Anderson Cancer Center initiative. Clin Cancer Res. 2012 Nov 15 ; 18 (22) : 6373-83. https://doi.org/10.1158/1078-0432.CCR-12-1627. Epub 2012 Sep 10. PMID: 22966018; PMCID: PMC4454458.
Beltran H, Eng K, Mosquera JM, Sigaras A, et al., Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response. JAMA Oncol. 2015 Jul ; 1 (4) : 466-74. https://doi.org/10.1001/jamaoncol.2015.1313. PMID: 26181256;PMCID:PMC4505739.
Massard C, Michiels S, Ferté C, et al. High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers : Results of the MOSCATO 01 Trial. Cancer Discov. 2017 ; 7 (6) : 586-595. https://doi.org/10.1158/2159-8290.CD-16-1396.
Kim ST, Lee J, Hong M, et al. The NEXT-1 (Next generation pErsonalized tX with mulTi-omics and preclinical model) trial : prospective molecular screening trial of metastatic solid cancer patients, a feasibility analysis. Oncotarget. 2015 ; 6 (32) : 33358-33368. https://doi.org/10.18632/oncotarget.5188.
Mathew A, Joseph S, Boby J, et al., Clinical Benefit of Comprehensive Genomic Profiling for Advanced Cancers in India. JCO Glob Oncol. 2022 Mar ; 8 : e2100421. https://doi.org/10.1200/GO.21.00421.
А.Д. Каприн, В.В. Старинский, А.О. Шахзадова. Злокачественные новообразования в России в 2021 году (заболеваемость и смертность) - М. : МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2022.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020 : GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021.
Dienstmann R, Connor K, Byrne AT ; COLOSSUS Consortium. Precision Therapy in RAS Mutant Colorectal Cancer. Gastroenterology. 2020 Mar ; 158 (4) : 806-811. https://doi.org/10.1053/j.gastro.2019.12.051.
Voutsadakis IA, Digklia A. Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CD-KN2A / CDKN2B copy number alterations : a review of the genomic landscape to unveil therapeutic avenues. Chin Clin Oncol. 2023.
Behl A., Rothe M., Magnat P., et al. Olaparib (O) in patients (pts) with colorectal cancer (CRC) with ATM mutation (mut) : Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study. https://doi.org/10.1200/JCO.2023.41.4_suppl.122 Journal of Clinical Oncology 41, no. 4_suppl (February 01, 2023) 122-122.
Lee J, Kim ST, Kim K, et al., Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment : The VIKTORY Umbrella Trial. Cancer Discov. 2019 Oct ; 9 (10) : 1388-1405. https://doi.org/10.1158/2159-8290.CD-19-0442.
Wang K, Kan J,Yuen ST et al. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet 2011 ; 43 : 1219-1223.
Dulak AM, Schumacher SE, van Lieshout J et al. Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res 2012 ; 72 : 4383-4393.
DengN,Goh LK,Wang Hetal. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 2012 ; 61 : 673-684.
Ali SM, Sanford EM, Klempner SJ et al., Prospective comprehensive genomic profiling of advanced gastric carcinoma cases reveals frequent clinically relevant genomic alterations and new routes for targeted therapies. Oncologist. 2015 May ; 20 (5) : 499-507. https://doi.org/10.1634/theoncologist.2014-0378.
Van Cutsem E, Bang YJ, Mansoor W, et al., A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification. Ann Oncol. 2017.
Rha S., Lee C.,Kim H. et al. The first report of K-Umbrella Gastric Cancer Study : An open label, multi-center, randomized, biomarker-integrated trial for second-line treatment of advanced gastric cancer (AGC). https://doi.org/10.1200/JCO.2022.40.16_suppl.4001 Journal of Clinical Oncology 40, no. 16_suppl (June 01, 2022) 4001-4001.
Sartore-Bianchi A, Amatu A, Porcu L, et al. HER2 Positivity Predicts Unresponsiveness to EGFR-Targeted Treatment in Metastatic Colorectal Cancer. Oncologist. 2019 Oct ; 24 (10) : 1395-1402. https://doi.org/10.1634/theoncologist.2018-0785.
Dazio G, Epistolio S, Frattini M, et al.Recent and Future Strategies to Overcome Resistance to Targeted Therapies and Immunotherapies in Metastatic Colorectal Cancer. J Clin Med. 2022 Dec 19 ; 11 (24) : 7523. https://doi.org/10.3390/jcm11247523.
Shitara K., Negative hyperselection of patients with RAS wildtype metastatic colorectal cancer for panitumumab : A biomarker study of the phase III PARADIGM trial, J Clin Oncol 41, 2023 (suppl 4 ; abstr 11), https://doi.org/10.1200/JCO.2023.41.4_suppl.11.
Федянин М.Ю., Трякин А.А., Тюляндин С.А. Потенциальные предикторы эффективности анти-EGFR-терапии при метастатическом раке толстой кишки // Онкологическая колопроктология 2013, № 2, стр. 21-30.
Kato S, Schwaederle MC, Fanta PT, et al : Genomic assessment of blood-derived circulating tumor DNA in patients with colorectal cancers : Correlation with ´ tissue sequencing, therapeutic response, and survival. JCO Precis Oncol 3 : 1-16, 2019.
Pishvaian MJ, Bender RJ, Halverson D, et al : Molecular profiling of patients with pancreatic cancer : Initial results from the Know Your Tumor initiative. Clin Cancer Res 24 : 5018-5027, 2018.
Pishvaian MJ, Blais EM, Brody JR, et al : Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling : A retrospective analysis of the Know Your Tumor registry trial. Lancet Oncol 21 : 508-518, 2020.
Schultheis, B. et al. Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer : a multicenter, randomized phase IIb study. Ann. Oncol. https://doi.org/10.1093/annonc/mdx343 (2017).
Qin S, Bai Y, Wang Z, et al. Nimotuzumab combined with gemcitabine versus gemcitabine in KRAS wild-type locally advanced or metastatic pancreatic cancer : A prospective, randomized-controlled, double-blinded, multicenter, and phase III clinical trial. J Clin Oncol. 2022 ; 40 (suppl 17) : LBA4011. https://doi.org/10.1200/JCO.2022.40.17_suppl.LBA4011.
Shroff RT, Hendifar A, McWilliams RR, et al. Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation. JCO Precis Oncol 2018 ; published online May 16. https://doi.org/10.1200/PO.17.00316.
Domchek SM, Aghajanian C, Shapira-Frommer R, et al. Efficacy and safety of olaparib monotherapy in germline BRCA1 / 2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol 2016 ; 140 : 199-203.
Lowery MA, Kelsen DP, Stadler ZK, et al. An emerging entity : pancreatic adenocarcinoma associated with a known BRCA mutation : clinical descriptors, treatment implications, and future directions. Oncologist 2011 ; 16 : 1397-402.
Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 2019 ; 381 : 317-27.
Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability / mismatch repair-deficient cancer : results from the phase 2 KEYNOTE-158 study. J Clin Oncol 2020 ; 38 : 1-10.
Salama AKS, Li S, Macrae ER, et al. Dabrafenib and Trametinib in Patients With Tumors With BRAF V600E Mutations : Results of the NCI-MATCH Trial Subprotocol H. J Clin Oncol 2020 ; 38 : 3895-3904. 20.
Subbiah V, Lassen U, Élez E, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR) : a phase 2, open-label, singlearm, multicentre basket trial. Lancet Oncol. 2020 ; 21 : 1234-1243.
Subbiah V, Wolf J, Konda B, et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001) : a phase 1 / 2, open-label, basket trial. Lancet Oncol. 2022 ; 23 : 1261-1273.
Laetsch TW, DuBois SG, Mascarenhas L, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions : phase 1 results from a multicentre, open-label, phase 1 / 2 study. Lancet Oncol 2018 ; 19 : 705-14.
Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. Final overall survival efcacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation : the phase 3 randomized clinical ClarIDHy trial. JAMA Oncol. 2021 ; 7 (11) : 1669-77.
Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, AlRajabi R, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma : a multicentre, open-label, phase 2 study. Lancet Oncol. 2020 ; 21 (5) : 671-84.
Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, et al. FOENIX-CCA2 : a phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements. J Clin Oncol. 2020 ; 38 (15_suppl) : 108.
Harding JJ, Fan J, Oh DY, Choi HJ, Kim JW, Chang HM, et al. Zanidatamab for HER2-amplifed, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01) : a multicentre, single-arm, phase 2b study. Lancet Oncol. 2023 ; 24 (7) : 772-82.
Bekaii-Saab TS, Bridgewater J, Normanno N. Practical considerations in screening for genetic alterations in cholangiocarcinoma. Ann Oncol. 2021 Sep ; 32 (9) : 1111-1126. https://doi.org/10.1016/j.annonc.2021.04.012. Epub 2021 Apr 28. PMID: 33932504.
Zhang D, Dorman K, Heinrich K, et al., A Retrospective Analysis of Biliary Tract Cancer Patients Presented to the Molecular Tumor Board at the Comprehensive Cancer Center Munich. Target Oncol. 2023 Sep ; 18 (5) : 767-776. https://doi.org/10.1007/s11523-023-00985-3.
Hyman DM, Taylor BS, Baselga J : Implementing genome-driven oncology. Cell 168 : 584-599, 2017.

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