Les conjugués anticorps-médicaments dans la prise en charge du carcinome urothélial avancé
Résumé
La pierre angulaire du traitement du carcinome urothélial avancé (CUa) a consisté, pendant des décennies, à utiliser des protocoles de chimiothérapie à base de platine, tels que le GC (gemcitabine avec cisplatine/carboplatine) ou le MVAC (méthotrexate, vinblastine, doxorubicine et cisplatine). Par la suite, les inhibiteurs de point de contrôle immunitaire (IPCI) ont été intégrés au standard de soins, d’abord en monothérapie lors de la rechute, et plus récemment, en tant que traitement d’entretien après la chimiothérapie de première intention. Puis récemment, le développement des conjugués anticorps-médicaments (CAM) a bouleversé le paysage thérapeutique du CUa.
Les CAM sont conçus pour agir comme un « missile de précision » biologique, dans le but de délivrer sa charge cytotoxique à la cellule cancéreuse cible tout en restant stable dans la circulation et en minimisant la toxicité hors cible. L’enfortumab védotine a été le premier à démontrer son efficacité dans le carcinome urothélial (CU), d’abord en monothérapie, puis en association avec un IPCI, surpassant ainsi le standard de chimiothérapie de première ligne, en vigueur depuis des décennies. Cette revue a pour but de discuter de l’évolution du domaine des CAM dans le CUa, en soulignant les principales cibles, les données cliniques, les toxicités et les opportunités à venir.
Références
von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068-77.
Cardenas L, Dibajnia P, Lalani AK. The emerging treatment landscape of advanced urothelial carcinoma. Curr Opin Support Palliat Care. 2021;15(4):247-52.
Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017;376(11):1015-26.
Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020;383(13):1218-30.
van der Heijden MS, Sonpavde G, Powles T, Necchi A, Burotto M, Schenker M, et al. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2023;389(19):1778-89.
Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduction and Targeted Therapy. 2022;7(1):93.
Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Duran I, Lee JL, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021;384(12):1125-35.
Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024;390(10):875-88.
Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat Rev Clin Oncol. 2021;18(6):327-44.
Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the "biological missile" for targeted cancer therapy. Signal Transduct Target Ther. 2022;7(1):93.
Tarantino P, Ricciuti B, Pradhan SM, Tolaney SM. Optimizing the safety of antibody-drug conjugates for patients with solid tumours. Nat Rev Clin Oncol. 2023;20(8):558-76.
Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. NECTIN4. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.
Heath EI, Rosenberg JE. The biology and rationale of targeting nectin-4 in urothelial carcinoma. Nat Rev Urol. 2021;18(2):93-103.
Rosenberg JE, Powles T, Sonpavde GP, Loriot Y, Duran I, Lee JL, et al. EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. Ann Oncol. 2023;34(11):1047-54.
Yu EY, Petrylak DP, O'Donnell PH, Lee JL, van der Heijden MS, Loriot Y, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):872-82.
Witjes JA, Bruins HM, Carrión A, Cathomas R, Compérat EM, Efstathiou JA, et al. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. Arnhem, The Netherlands.: European Association of Urology; 2024.
Shah Y, Sher AF, Wu S. Incidence and risk of peripheral sensory neuropathy with enfortumab vedotin in patients with advanced urothelial cancer: A systematic review and meta-analysis. Journal of Clinical Oncology. 2023;41(16_suppl):e16556-e.
Peng J, Hueniken K, Proulx-Rocray F, Alimohamed NS, Fallah-rad N, Kumar V, et al. Real-world evidence for enfortumab vedotin (EV) in metastatic urothelial carcinoma (mUC): a multi-centred observational study in a publicly funded Canadian system. Journal of Clinical Oncology. 2024;42(16_suppl):e16566-e.
Lacouture ME, Patel AB, Rosenberg JE, O’Donnell PH. Management of Dermatologic Events Associated With the Nectin-4-directed Antibody-Drug Conjugate Enfortumab Vedotin. The Oncologist. 2022;27(3):e223-e32.
Cheng R, Boparai M, Wu S. Increased risk of hyperglycemia in patients with advanced urothelial cancer treated with enfortumab vedotin: A systematic review and meta-analysis. Journal of Clinical Oncology. 2024;42(16_suppl):e15001-e.
Ye D-W, Zhang J, Yang H, Yang J, Zheng T, Sun H, et al. Clinical update related to the first-in-human trial of SYS6002 (CRB-701), a next-generation nectin-4 targeting antibody drug conjugate. Journal of Clinical Oncology. 2024;42(16_suppl):3151-.
Rosenberg J, Sabatier R, Viceneux A, Rouge TdLM, Champiat S, Lebellec L, et al. Abstract CT084: A phase 1 study of LY4101174 (ETx-22), an antibody-drug conjugate targeting nectin-4, in patients with advanced or metastatic urothelial cancer and other solid tumors (trial in progress). Cancer Research. 2024;84(7_Supplement):CT084-CT.
Baldini C, Goldschmidt V, Brana I, Doger B, Italiano A, Cousin S, et al. BT8009-100: A phase I/II study of novel bicyclic peptide and MMAE conjugate BT8009 in patients (pts) with advanced malignancies associated with nectin-4 expression, including urothelial cancer (UC). Journal of Clinical Oncology. 2023;41(6_suppl):498-.
Loriot Y, Siefker-Radtke AO, Friedlander TW, Necchi A, Wei AZ, Sridhar SS, et al. A phase 2/3 study of Bicycle toxin conjugate BT8009 targeting nectin-4 in patients with locally advanced or metastatic urothelial cancer (la/mUC): Duravelo-2. Journal of Clinical Oncology. 2024;42(16_suppl):TPS4619-TPS.
Chow NH, Chan SH, Tzai TS, Ho CL, Liu HS. Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder. Clin Cancer Res. 2001;7(7):1957-62.
Scherrer E, Kang A, Bloudek LM, Koshkin VS. HER2 expression in urothelial carcinoma, a systematic literature review. Frontiers in Oncology. 2022;12.
Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20.
FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors: US Food and Drug Administration; 2024 [Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2.
Sheng X, Yan X, Wang L, Shi Y, Yao X, Luo H, et al. Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody–Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma. Clinical Cancer Research. 2021;27(1):43-51.
Sheng X, He Z, Han W, Zhou A-P, Luo H, Shi Y, et al. An open-label, single-arm, multicenter, phase II study of RC48-ADC to evaluate the efficacy and safety of subjects with HER2 overexpressing locally advanced or metastatic urothelial cancer (RC48-C009). Journal of Clinical Oncology. 2021;39(15_suppl):4584-.
Galsky MD, Grande E, Necchi A, Koontz MZ, Iyer G, Campbell MT, et al. Phase 3 open-label, randomized, controlled study of disitamab vedotin with pembrolizumab versus chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma that expresses HER2 (DV-001). Journal of Clinical Oncology. 2024;42(4_suppl):TPS717-TPS.
Ma Y, Huang Y, Zhao Y, Zhao S, Xue J, Yang Y, et al. BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol. 2024;25(7):901-11.
Ye D-W, Bian X, Yang T, Jiang S, Cao M, Xiao S, et al., editors. BL-B01D1, an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic urothelial carcinoma (UC). Ann Oncol; 2024 13 Sep 2024.
Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018;9(48).
Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. New England Journal of Medicine. 2021;384(16):1529-41.
Tagawa ST, Balar AV, Petrylak DP, Rezazadeh A, Loriot Y, Flechon A, et al. Updated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Journal of Clinical Oncology. 2023;41(6_suppl):526-.
FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer: US Food and Drug Administration; 2021 [Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer.
Tagawa ST, Balar AV, Petrylak DP, Kalebasty AR, Loriot Y, Fléchon A, et al. TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. J Clin Oncol. 2021;39(22):2474-85.
Petrylak DP, Tagawa ST, Jain RK, Bupathi M, Balar AV, Rezazadeh A, et al. Primary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan (SG) in platinum (PT)-ineligible patients (pts) with metastatic urothelial cancer (mUC) that progressed after prior checkpoint inhibitor (CPI) therapy. Journal of Clinical Oncology. 2023;41(6_suppl):520-.
Gilead Provides Update on Phase 3 TROPiCS-04 Study: Gilead Sciences; 2024 [Available from: https://www.gilead.com/news-and-press/press-room/press-releases/2024/5/gilead-provides-update-on-phase-3-tropics-04-study.
Grivas P, Pouessel D, Park CH, Barthelemy P, Bupathi M, Petrylak DP, et al. Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3. J Clin Oncol. 2024:JCO2202835.
Lisberg A, Drakaki A, Meric-Bernstam F, Alhalabi O, Kojima T, Kato M, et al. Datopotamab deruxtecan in locally advanced/metastatic urothelial cancer: Preliminary results from the phase 1 TROPION-PanTumor01 study. Journal of Clinical Oncology. 2024;42(4_suppl):603-.
Janjigian YY, Oaknin A, Lang JM, Ciombor KK, Ray-Coquard IL, Oza AM, et al. TROPION-PanTumor03: Phase 2, multicenter study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients (pts) with advanced/metastatic solid tumors. Journal of Clinical Oncology. 2023;41(16_suppl):TPS3153-TPS.
Loriot Y, Petrylak DP, Rezazadeh A, Flechon A, Jain RK, Gupta S, et al. Safety analysis by UGT1A1 status of TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Journal of Clinical Oncology. 2023;41(16_suppl):4514-.
Jindal T, Jiang CY, Alhalabi O, Nguyen CB, Nizam A, Basu A, et al. Outcomes with enfortumab vedotin in patients with advanced urothelial carcinoma and histology variants: Analysis of the UNITE study. Journal of Clinical Oncology. 2024;42(4_suppl):652-.
Nazha B, Brown JT, Liu Y, Kissick H, Carthon BC, Kucuk O, et al. Enfortumab vedotin plus pembrolizumab in the treatment of locally advanced or metastatic bladder cancer of variant histology: A phase II study. Journal of Clinical Oncology. 2024;42(16_suppl):TPS4615-TPS.
Klümper N, Ralser DJ, Ellinger J, Roghmann F, Albrecht J, Below E, et al. Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance. Clin Cancer Res. 2023;29(8):1496-505.
Chang K, Lodha R, Delavan HM, Winebaum J, Porten SP, Feng FY, et al. Mechanisms and strategies to overcome resistance to enfortumab vedotin in bladder cancer. Journal of Clinical Oncology. 2024;42(4_suppl):690-.
Sternschuss M, Toumbacaris N, Das JP, Powles T, Bajorin DF, Kotecha RR, et al. Clinical outcomes of sacituzumab govitecan (SG) after prior exposure to enfortumab vedotin (EV) in patients with metastatic urothelial carcinoma (mUC). Journal of Clinical Oncology. 2024;42(16_suppl):4581-.
McGregor BA, Kwak L, Sonpavde GP, Berg SA, CHOUEIRI TK, Bellmunt J, et al. Sacituzumab govitecan (SG) plus enfortumab vedotin (EV) for metastatic urothelial carcinoma (mUC) treatment-experienced (DAD) and with pembrolizumab (P) in treatment naïve UC (DAD-IO). Journal of Clinical Oncology. 2024;42(16_suppl):TPS4618-TPS.
Jain RK, Heiligh J, Kim Y, Piekarz R, Pelosof LC, Yang Y, et al. Phase Ib trial of erdafitinib (E) combined with enfortumab vedotin (EV) following platinum and PD-1/L1 inhibitors for metastatic urothelial carcinoma (mUC) with FGFR2/3 genetic alterations (GAs). Journal of Clinical Oncology. 2024;42(4_suppl):625-.
Brown JT, Nazha B, Liu Y, Ranbhise S, Lozada K, Hartman C, et al. Interim analysis of a phase I/Ib study of enfortumab vedotin plus cabozantinib in patients with metastatic urothelial carcinoma. Journal of Clinical Oncology. 2024;42(4_suppl):609-.
Funt SA, Grivas P, Gao X, Vaena DA, Zhang T, Milowsky MI, et al. Evorpacept plus enfortumab vedotin in patients (Pts) with locally advanced or metastatic urothelial carcinoma (la/mUC): Phase 1a dose escalation results. Journal of Clinical Oncology. 2024;42(16_suppl):4575-.
Publié
Comment citer
Numéro
Rubrique
Licence
© Canadian Oncology Today 2024
Cette œuvre est sous licence Creative Commons Attribution - Pas d'Utilisation Commerciale - Pas de Modification 4.0 International.
