Enfortumab vedotin as a salvage option as 5th line therapy for metastatic urothelial bladder cancer

Abstract

A 67-year-old female patient with a muscle-invasive, non-metastatic urothelial bladder cancer (UC) (pT2 G3 cN0 cM0) developed metachronous metastases within 6 months after radical cystectomy with ileal conduit urinary diversion.

After a good primary response to platinum-based chemotherapy, treatment was switched to the immune checkpoint inhibitor (ICI) pembrolizumab due to progressive disease. Subsequently the patient underwent selective internal radiotherapy (SIRT) of the liver and received vinflunine as well as a re-challenge with pembrolizumab.

Two years after the initial diagnosis, rapid disease progression ultimately led to a switch to 5th line therapy with enfortumab vedotin (EV), which had only been approved in the United States at that time. The antibody-drug conjugate was well tolerated by the patient after dose reduction to 1.0 mg/ kg body weight. Simultaneous irradiation of newly occurring precardiac, hepatic and cerebral metastases were necessary. After 10 months of therapy with EV, tumour regression was observed accompanied with good symptom control.

The presented case illustrates the efficacy and tolerability of EV in a heavily pre-treated patient with metastatic UC (mUC).

Zusammenfassung

Eine 67-jährige Patientin mit Urothelkarzinom (UC) der Harnblase entwickelte nach kurativer radikaler Zystektomie mit Ileumconduit-Anlage (pT2 N0 M0) einen Frühprogress mit metachroner Metastasierung. Nach primär gutem Ansprechen auf eine platinhaltige Chemotherapie erfolgte bei Progress eine Zweitlinientherapie mit dem Checkpointinhibitor Pembrolizumab. Bei erneut isoliert hepatischem Metastasennachweis kam nach selektiver interner Radiotherapie (SIRT), bei nochmaligem Progress Vinflunin und in rascher Folge wiederholt Pembrolizumab zum Einsatz. Knapp 2 Jahre nach Erstdiagnose erfolgte bei fortschreitender Tumorerkrankung ein Therapiewechsel auf das bis dato nur in den USA zugelassene Enfortumab Vedotin. Das Antikörper-Drug-Konjugat wurde von der Patientin in reduzierter Dosierung (1mg/ kg KG) gut vertragen. Zwischenzeitlich wurden simultan Bestrahlungen neu aufgetretener präkardialer, hepatischer sowie einer zerebralen Metastase notwendig. Nach 10-monatiger Therapielaufzeit war ein Tumorregress bei guter Symptomkontrolle zu verzeichnen.

Enfortumab Vedotin zeigte hier bei intensiv vorbehandelter Patientin eine gute Verträglichkeit sowie Wirkung beim M1 UC der Harnblase. Entsprechend unterstreicht der Fall, dass der Einsatz von Medikamenten, die zunächst nur im Ausland zugelassen sind, für entsprechend vorbehandelte Krebspatienten mit gutem Performance-Status, als individueller Heilversuch in Betracht gezogen werden sollte.

Keywords

urothelial bladder cancer - enfortumab vedotin - metachronic metastases - antibody-drug conjugate - immunotherapy

Schlüsselwörter

Urothelkarzinom - Enfortumab Vedotin - Antikörper-Drug-Konjugat - metachrone Metastasierung - Immuntherapie

• References

• 1 Krebs – Krebs in Deutschland – Harnblase – C67 [Internet]. [cited 2022 Mar 3]. Available from. https://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/kid_2019/kid_2019_c67_harnblase.pdf
• 2 Saginala K, Barsouk A, Aluru JS. et al. Epidemiology of Bladder Cancer. Med Sci 2020; 8: 15
• 3 von der Maase H, Hansen SW, Roberts JT. 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 Off J Am Soc Clin Oncol 2000; 18: 3068-3077
• 4 Bellmunt J, de Wit R, Vaughn DJ. et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017; 376: 1015-1026
• 5 Balar AV, Galsky MD, Rosenberg JE. et al. Atezolizumab as first-line therapy in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet Lond Engl 2017; 389: 67-76
• 6 Bajorin DF, Witjes JA, Gschwend JE. et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med 2021; 384: 2102-2114
• 7 Powles T, O’Donnell PH, Massard C. et al. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma. JAMA Oncol 2017; 3: e172411
• 8 Apolo AB, Infante JR, Balmanoukian A. et al. Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study. J Clin Oncol 2017; 35: 2117-2124
• 9 Merseburger AS, Apolo AB, Chowdhury S. et al. SIU-ICUD recommendations on bladder cancer: systemic therapy for metastatic bladder cancer. World J Urol 2019; 37: 95-105
• 10 Facchinetti F, Hollebecque A, Bahleda R. et al. Facts and new hopes on selective FGFR inhibitors in solid tumors. Clin Cancer Res Off J Am Assoc Cancer Res 2020; 26: 764-774
• 11 Goldenberg DM, Sharkey RM. Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: A case study of anti-TROP-2 sacituzumab govitecan. mAbs 2019; 11: 987-995
• 12 Rosenberg JE, O’Donnell PH, Balar 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 2019; 37: 2592-2600
• 13 Alt M, Stecca C, Tobin S. et al. Enfortumab Vedotin in urothelial cancer. Ther Adv Urol 2020; 12: 1756287220980192
• 14 Powles T, Rosenberg JE, Sonpavde GP. et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021; 384: 1125-1135
• 15 Fradet Y, Bellmunt J, Vaughn 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 Off J Eur Soc Med Oncol 2019; 30: 970-976
• 16 Koshkin VS, Osbourne AS, Grivas P. Treatment options for advanced urothelial cancer after progression on chemotherapy and immune checkpoint inhibitors: a literature review. Transl Androl Urol 2021; 10: 4022-4035
• 17 Challita-Eid PM, Satpayev D, Yang P. et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016; 76: 3003-3013
• 18 Hanna KS. Advancements in Therapy for Bladder Cancer: Enfortumab Vedotin. J Adv Pract Oncol 2020; 11: 412-417
• 19 Rosenberg JE, Flaig TW, Friedlander TW. et al. Study EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. J Clin Oncol 2020; 38 (Suppl. 06) 441-441
• 20 Lavoie J, Sridhar SS, Ong M. et al. The Rapidly Evolving Landscape of First. Line Targeted Therapy in Metastatic Urothelial Cancer: A Systematic Review. The Oncologist 2021; 26: e1381-e1394