Zie ook literatuurlijst niet-toxische medicijnen en behandelingen specifiek bij blaaskanker van arts-bioloog drs. Engelbert Valstar.

12 mei 2021: Bron: Journalo of Clinical Oncology

Sacituzumab govitecan , een medicijn dat voor uitgezaaide borstkanker stadium 4 officieel is goedgekeurd, geeft bij patiënten met lokaal gevorderde inoperabele of uitgezaaide urineleiderkanker - blaaskanker met progressie van hun ziekte na eerdere op platina gebaseerde chemo en immuuntherapie met anti-PD medicijnen alsnog uitstekende resultaten met zelfs enkele complete remissies erbij. 

Het totale responspercentage was 27,4%, inclusief 5,3% complete remissies en 22,1% gedeeltelijke remissies. Bij 33,6% van de patiënten werd stabiele ziekte waargenomen. De mediane responsduur was 7,2 maanden en de mediane totale overleving was 10,9 maanden. De therapie werd goed verdragen, met als meest voorkomende behandelingsgerelateerde bijwerkingen van graad 3 neutropenie, leukopenie, bloedarmoede - anemie, diarree en febriele neutropenie.

(Sacituzumab govitecan is een antilichaam-geneesmiddelconjugaat dat bestaat uit een antilichaam dat zich richt op het menselijke Trophoblast cell surface antigen 2 (Trop-2), dat tot expressie komt in de meeste borstkankers, gekoppeld aan SN-38 (een topoisomerase I-remmer))

De onderzoekers stellen voor om bij deze groep van zwaarvoorbehandelde blaaskankerpatiënten Sacituzumab govitecan toe te voegen aan een behandelingsprotocol. 

Het volledige studierapport is gratis in te zien. Klik op de titel van het abstract:


Genitourinary Cancer

Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2–directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label, phase II, registrational study. Cohort 1 includes patients with locally advanced or unresectable or mUC who had progressed after prior PLT and CPI. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary outcome was centrally reviewed ORR; secondary outcomes were progression-free survival, OS, duration of response, and safety.

Cohort 1 included 113 patients (78% men; median age, 66 years; 66.4% visceral metastases; median of three [range, 1-8] prior therapies). At a median follow-up of 9.1 months, the ORR was 27% (31 of 113; 95% CI, 19.5 to 36.6); 77% had decrease in measurable disease. Median duration of response was 7.2 months (95% CI, 4.7 to 8.6 months), with median progression-free survival and OS of 5.4 months (95% CI, 3.5 to 7.2 months) and 10.9 months (95% CI, 9.0 to 13.8 months), respectively. Key grade ≥ 3 treatment-related adverse events included neutropenia (35%), leukopenia (18%), anemia (14%), diarrhea (10%), and febrile neutropenia (10%), with 6% discontinuing treatment because of treatment-related adverse events.

SG is an active drug with a manageable safety profile with most common toxicities of neutropenia and diarrhea. SG has notable efficacy compared with historical controls in pretreated mUC that has progressed on both prior PLT regimens and CPI. The results from this study supported accelerated approval of SG in this population.

1. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer Version 5.2020. https://www.nccn.org/professionals/physician_gls/ Google Scholar
2. Petrylak DPde Wit RChi KN, et al: Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): A randomised, double-blind, phase 3 trial. Lancet 390:2266-22772017 CrossrefMedlineGoogle Scholar
3. Raggi DMiceli RSonpavde G, et al: Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: A systematic review and meta-analysis. Ann Oncol 27:49-612016 CrossrefMedlineGoogle Scholar
4. Niegisch GGerullis HLin SW, et al: A real-world data study to evaluate treatment patterns, clinical characteristics and survival outcomes for first- and second-line treatment in locally advanced and metastatic urothelial cancer patients in Germany. J Cancer 9:1337-13482018 CrossrefMedlineGoogle Scholar
5. Fradet YBellmunt JVaughn DJ, et al: Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: Results of > 2 years of follow-up. Ann Oncol 30:970-9762019 CrossrefMedlineGoogle Scholar
6. Di Lorenzo GBuonerba CBellelli T, et al: Third-line chemotherapy for metastatic urothelial cancer: A retrospective observational study. Medicine (Baltimore) 94:e22972015 CrossrefMedlineGoogle Scholar
7. Vlachostergios PJJakubowski CDNiaz MJ, et al: Antibody-drug conjugates in bladder cancer. Bladder Cancer 4:247-2592018 CrossrefMedlineGoogle Scholar
8. Padcev [Package Insert]. Northbrook, ILAstellas Pharma US2019 Google Scholar
9. FDA Grants Accelerated Approval to Enfortumab Vedotin-ejfv for Metastatic Urothelial Cancer [Press Release]. Silver Spring, MD: US Food and Drug Administration, December 19, 2019https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-enfortumab-vedotin-ejfv-metastatic-urothelial-cancer Google Scholar
10. Loriot YNecchi APark SH, et al: Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med 381:338-3482019 CrossrefMedlineGoogle Scholar
11. de Almeida Carvalho LMde Oliveira Sapori Avelar SHaslam A, et al: Estimation of percentage of patients with fibroblast growth factor receptor alterations eligible for off-label use of erdafitinib. JAMA Netw Open 2:e19160912019 CrossrefMedlineGoogle Scholar
12. Trerotola MCantanelli PGuerra E, et al: Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene 32:222-2332013 CrossrefMedlineGoogle Scholar
13. Avellini CLicini CLazzarini R, et al: The trophoblast cell surface antigen 2 and miR-125b axis in urothelial bladder cancer. Oncotarget 8:58642-586532017 CrossrefMedlineGoogle Scholar
14. Shvartsur ABonavida BTrop2 and its overexpression in cancers: Regulation and clinical/therapeutic implications. Genes Cancer 6:84-1052015 CrossrefMedlineGoogle Scholar
15. Stepan LPTrueblood ESHale K, et al: Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: Potential implications as a cancer therapeutic target. J Histochem Cytochem 59:701-7102011 CrossrefMedlineGoogle Scholar
16. Goldenberg DMStein RSharkey RMThe emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget 9:28989-290062018 CrossrefMedlineGoogle Scholar
17. Muhlmann GSpizzo GGostner J, et al: TROP2 expression as prognostic marker for gastric carcinoma. J Clin Pathol 62:152-1582009 CrossrefMedlineGoogle Scholar
18. Ohmachi TTanaka FMimori K, et al: Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res 12:3057-30632006 CrossrefMedlineGoogle Scholar
19. Fang YJLu ZHWang GQ, et al: Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. Int J Colorectal Dis 24:875-8842009 CrossrefMedlineGoogle Scholar
20. Fong DSpizzo GGostner JM, et al: TROP2: A novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol 21:186-1912008 CrossrefMedlineGoogle Scholar
21. Fong DMoser PKrammel C, et al: High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer 99:1290-12952008 CrossrefMedlineGoogle Scholar
22. Fornaro MDell'Arciprete RStella M, et al: Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas. Int J Cancer 62:610-6181995 CrossrefMedlineGoogle Scholar
23. Stoyanova TGoldstein ASCai H, et al: Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via beta-catenin signaling. Genes Dev 26:2271-22852012 CrossrefMedlineGoogle Scholar
24. Arafat WStahlfeld CSperger JM, et al: Intra-patient heterogeneity in urothelial cancer (UC) circulating tumor cells (CTC) and PDL1 expression to identify biomarkers of response and new therapeutic targets: A pilot study. J Clin Oncol 35:45372017 (15 suppl; abstrLinkGoogle Scholar
25. Goldenberg DMCardillo TMGovindan SV, et al: Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget 6:22496-225122015 CrossrefMedlineGoogle Scholar
26. Cardillo TMGovindan SVSharkey RM, et al: Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: Preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res 17:3157-31692011 CrossrefMedlineGoogle Scholar
27. Cardillo TMGovindan SVSharkey RM, et al: Sacituzumab govitecan (IMMU-132), an anti-trop-2/SN-38 antibody-drug conjugate: Characterization and efficacy in pancreatic, gastric, and other cancers. Bioconjug Chem 26:919-9312015 CrossrefMedlineGoogle Scholar
28. Starodub ANOcean AJShah MA, et al: First-in-human trial of a novel anti-trop-2 antibody-SN-38 conjugate, sacituzumab govitecan, for the treatment of diverse metastatic solid tumors. Clin Cancer Res 21:3870-38782015 CrossrefMedlineGoogle Scholar
29. Govindan SVCardillo TMGoldenberg DMTopoisomerase inhibitors as antibody-drug conjugate payloads, in Thurston DEJackson PJM (eds): Cytotoxic Payloads for Antibody-Drug Conjugates. London, UK: The Royal Society of Chemistry2019, pp 166-186 CrossrefGoogle Scholar
30. Ocean AJStarodub ANBardia A, et al: Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Cancer 123:3843-38542017 CrossrefMedlineGoogle Scholar
31. Tagawa STFaltas BMLam ET, et al: Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study. J Clin Oncol 37:3542019 LinkGoogle Scholar
32. Faltas BGoldenberg DMOcean AJ, et al: Sacituzumab govitecan, a novel antibody—drug conjugate, in patients with metastatic platinum-resistant urothelial carcinoma. Clin Genitourin Cancer 14:e75-792016 CrossrefMedlineGoogle Scholar
33. Therasse PArbuck SGEisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-2162000 CrossrefMedlineGoogle Scholar
34. Tagawa STBalar APetrylak DP, et al: A phase 2 open-label study of sacituzumab govitecan in patients with metastatic urothelial cancer (mUC) after failure of platinum-based regimens or immunotherapy . Annual Meeting of the European Society for Medical Oncology. Barcelona, Spain, 2019 Google Scholar
35. Clopper CJPearson ESThe use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26:404-4131934 CrossrefGoogle Scholar
36. Bellmunt JChoueiri TKFougeray R, et al: Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens. J Clin Oncol 28:1850-18552010 LinkGoogle Scholar
37. Rosenberg JEO'Donnell PHBalar AV, et al: Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol 37:2592-26002019 LinkGoogle Scholar
38. Bellmunt JTheodore CDemkov T, et al: Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 27:4454-44612009 LinkGoogle Scholar
39. Krege SRembrink VBörgermann C, et al: Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: A phase 2 study. J Urol 165:67-712001 CrossrefMedlineGoogle Scholar
40. Sridhar SSBlais NTran B, et al: Cctg BL12: Randomized phase II trial comparing nab-paclitaxel (Nab-P) to paclitaxel (P) in patients (pts) with advanced urothelial cancer progressing on or after a platinum containing regimen (NCT02033993). J Clin Oncol 36:45052018 (15 suppl; abstrLinkGoogle Scholar
41. Bambury RMBenjamin DJChaim JL, et al: The safety and efficacy of single-agent pemetrexed in platinum-resistant advanced urothelial carcinoma: A large single-institution experience. Oncologist 20:508-5152015 CrossrefMedlineGoogle Scholar
42. Grivas PMortazavi APicus J, et al: Mocetinostat for patients with previously treated, locally advanced/metastatic urothelial carcinoma and inactivating alterations of acetyltransferase genes. Cancer 125:533-5402019 CrossrefMedlineGoogle Scholar
43. Grivas PLoriot YFeyerabend S, et al: Rucaparib for recurrent, locally advanced or metastatic urothelial carcinoma: Results from ATLAS, a phase 2, open-label trial [oral presentation], Annual Genitourinary Cancers Symposium. San Francisco, CA, 2020 Google Scholar
44. Rosenberg JEHoffman-Censits JPowles T, et al: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 387:1909-19202016 CrossrefMedlineGoogle Scholar
45. Powles TO'Donnell PHMassard C, et al: Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: Updated results from a phase 1/2 open-label study. JAMA Oncol 3:e1724112017 CrossrefMedlineGoogle Scholar
46. Patel MREllerton JInfante JR, et al: Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN solid tumor): Pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 19:51-642018 CrossrefMedlineGoogle Scholar
47. Bellmunt Jde Wit RVaughn DJ, et al: Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376:1015-10262017 CrossrefMedlineGoogle Scholar
48. Sharma PSiefker-Radtke Ade Braud F, et al: Nivolumab alone and with ipilimumab in previously treated metastatic urothelial carcinoma: CheckMate 032 nivolumab 1 mg/kg plus ipilimumab 3 mg/kg expansion cohort results. J Clin Oncol 37:1608-16162019 LinkGoogle Scholar
49. Barata PCGopalakrishnan DKoshkin VS, et al: Atezolizumab in metastatic urothelial carcinoma outside clinical trials: Focus on efficacy, safety, and response to subsequent therapies. Target Oncol 13:353-3612018 CrossrefMedlineGoogle Scholar
50. Rosenberg JESridhar SSZhang J, et al: Mature results from EV-101: a phase I study of enfortumab vedotin in patients with metastatic urothelial cancer (mUC). J Clin Oncol 37:3772019 (suppl 7S; abstrLinkGoogle Scholar
51. Seattle Genetics and Astellas Announce PADCEV® (Enfortumab Vedotin-ejfv) Significantly Improved Overall Survival in Phase 3 Trial in Previously Treated Locally Advanced or Metastatic Urothelial Cancer [Press Release]. Bothell, WA: Seattle Genetics2020https://www.astellas.com/en/news/16026 Google Scholar
52. Trodelvy [package Insert]. Morris Plains, NJImmunomedics,2020 Google Scholar
53. Bardia AMayer IAVahdat LT, et al: Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med 380:741-7512019 CrossrefMedlineGoogle Scholar
54. Gray JEHeist RSStarodub AN, et al: Therapy of small cell lung cancer (SCLC) with a topoisomerase-I-inhibiting antibody-drug conjugate (ADC) targeting Trop-2, sacituzumab govitecan. Clin Cancer Res 23:5711-57192017 CrossrefMedlineGoogle Scholar
55. Heist RSGuarino MJMasters G, et al: Therapy of advanced non-small-cell lung cancer with an SN-38-anti-Trop-2 drug conjugate, sacituzumab govitecan. J Clin Oncol 35:2790-27972017 LinkGoogle Scholar
56. Trodelvy [package insert]. Morris Plains, NJ, Immunomedics, Inc, 2021 Google Scholar
57. Bardia AHurvitz SATolaney SM, et al: Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med (in press) Google Scholar
58. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer [press release]. Silver Spring, MD: US Food and Drug Administration, April 13, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer Google Scholar

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