Temporary Tumor Shrinkage Following Enfortumab Vedotin Therapy for Metastatic Urothelial Carcinoma After Radical Cystectomy With Neoadjuvant Chemotherapy: A Case Report DOI Open Access

Sanae Namiki,

Daiki Kato, Koji Iinuma

et al.

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 4, 2023

A 39-year-old Japanese male patient presented with a chief complaint of gross hematuria persistent for two months. However, no relevant findings in the patient’s medical and family history were observed. He was diagnosed muscle-invasive bladder cancer, clinical stage T2bN0M0. After four courses neoadjuvant chemotherapy gemcitabine cisplatin, tumor size reduced by approximately 30%. The underwent robot-assisted radical cystectomy standard lymph node dissection followed intracorporeal ileal conduit reconstruction. Histologically, as high-grade urothelial carcinoma invading fatty tissue surrounding metastasizing to nodes, pathological ypT3aypN2M0. Four months after surgery, multiple metastases detected, treatment pembrolizumab initiated immediately. did not respond pembrolizumab. Therefore, third-line enfortumab vedotin (EV) initiated. Thereafter, metastatic lesion shrank quickly, lesions almost disappeared EV administration. Although new observed at other sites, there has been regrowth date. EV-related adverse events during follow-up. Eighteen remains alive metastases. sequence should be considered maximize therapeutic effect EV, and, consequently, administering early possible may important.

Language: Английский

NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer DOI Creative Commons
Niklas Klümper, Ngoc Khanh Tran,

Stefanie Zschäbitz

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(20), P. 2446 - 2455

Published: April 24, 2024

PURPOSE The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit only achieved in a small, yet uncharacterized patient subset. NECTIN4 located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) cancer. Here, we aimed to evaluate amplifications as genomic biomarker predict EV response mUC. MATERIALS AND METHODS We established NECTIN4-specific fluorescence situ hybridization (FISH) assay assess the predictive value of CNVs multicenter EV-treated mUC cohort (mUC-EV, n = 108). were correlated membranous protein expression, treatment responses, outcomes. also assessed prognostic measured biopsies non–EV-treated (mUC-non-EV, 103). Furthermore, queried Cancer Genome Atlas (TCGA) data sets (10,712 across 32 types) CNVs. RESULTS are events muscle-invasive bladder (TCGA set: approximately 17%) (approximately 26% our cohorts). In mUC-EV, amplification represents stable alteration during progression associates enhanced expression. Ninety-six percent (27 28) demonstrated objective responses compared 32% (24 74) nonamplified subgroup ( P < .001). multivariable Cox analysis adjusted age, sex, Bellmunt risk factors, led 92% reduction death (hazard ratio, 0.08 [95% CI, 0.02 0.34]; mUC-non-EV, not associated TCGA Pan-Cancer that occur frequently other cancers, example, 5%-10% breast lung cancers. CONCLUSION predictors long-term survival

Language: Английский

Citations

28
Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort DOI
Makito Miyake, Nobutaka Nishimura,

Yuki Oda

et al.

Japanese Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 54(3), P. 329 - 338

Published: Nov. 20, 2023

Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events patients receiving vedotin.

Language: Английский

Citations

23
Enfortumab vedotin prolongs overall survival in metastatic urothelial carcinoma following pembrolizumab therapy in real‐world data DOI
K Uemura, Hiroki Ito, Ryosuke Jikuya

et al.

International Journal of Urology, Journal Year: 2024, Volume and Issue: 31(6), P. 678 - 684

Published: Feb. 25, 2024

Objective In December 2021, enfortumab vedotin (EV), an antibody‐drug conjugate directed against nectin‐4, was approved in Japan as a new treatment after platinum‐containing chemotherapy and PD‐1/PD‐L1 inhibitors. This study evaluated, using real‐world data, the efficacy safety of EV therapy patients with metastatic urothelial carcinoma (mUC). Materials methods Fifty‐five mUC who discontinued pembrolizumab due to disease progression between June 2018 April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of 55 patients, 25 received (EV group) 30 did not (non‐EV group). All underwent diagnosed approval Japan. Results The median (range) follow‐up period discontinuation 6.3 (0.7–31.1) months. There eight (32.0%) deaths cancer group 27 (90.0%) non‐EV group. overall survival (OS) reached versus 2.6 months ( p < 0.001). A multivariate analysis revealed that vs. group; hazard ratio 0.26; 95% confidence interval 0.16–0.41; 0.001) independent prognostic factor for OS. Conclusion prolonged OS following data.

Language: Английский

Citations

12
Prognostic Impact of Histologic Subtype and Divergent Differentiation in Patients with Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multicenter Retrospective Study DOI Creative Commons
Akinori Minato, Nobuki Furubayashi,

Yujiro Nagata

et al.

Current Oncology, Journal Year: 2024, Volume and Issue: 31(2), P. 862 - 871

Published: Feb. 3, 2024

Subtype of urothelial carcinoma (SUC), defined here as with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess oncological outcomes patients treated EV for metastatic We retrospectively evaluated consecutive advanced lower and upper urinary tract cancer who received after platinum-based chemotherapy immune checkpoint blockade therapy at six institutions. The objective response rate (ORR), progression-free survival (PFS), overall (OS) were compared between pure (PUC) those SUC. identified 44 18 PUC SUC, respectively. Squamous differentiation was most common element, followed by glandular sarcomatoid subtype. Although had comparable ORR PUC, duration short. Patients poorer PFS than PUC; however, no significant difference observed in OS. Multivariate analysis revealed that significantly associated shorter PFS. similar showed faster progression PUC.

Language: Английский

Citations

9
Clinical outcomes in patients with advanced urothelial carcinoma treated with enfortumab vedotin: A retrospective multicenter study in Japan DOI
Takuto Hara, Yuto Matsushita, Kenichi Harada

et al.

International Journal of Urology, Journal Year: 2024, Volume and Issue: 31(6), P. 696 - 698

Published: Feb. 29, 2024

None declared.

Language: Английский

Citations

9
Enfortumab vedotin–related cutaneous toxicity correlates with overall survival in patients with urothelial cancer: a retrospective experience DOI Creative Commons
Evangelia Vlachou, Burles A. Johnson, David J. McConkey

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 12, 2024

Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to human monoclonal targeting nectin-4. No validated biomarker predictive or correlated with response exists EV. Cutaneous toxicity among the most common EV-related toxicities and typically emerges in early cycles. This retrospective experience patients cancer treated EV monotherapy evaluated whether cutaneous improved outcomes including progression-free (PFS) overall (OS) survival rate (ORR).

Language: Английский

Citations

9
Influence of best objective response to first‐line treatment on survival outcomes in advanced urothelial carcinoma in the era of sequential therapy with enfortumab vedotin DOI Creative Commons
Kohei Kobatake, Keisuke Goto, Yuki Sakamoto

et al.

International Journal of Urology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Objective This study evaluated whether first‐line treatment affects survival outcomes in patients with advanced urothelial carcinoma undergoing sequential therapy chemotherapy, immune checkpoint inhibitors, and enfortumab vedotin. Methods multicenter retrospective included 57 treated at Hiroshima University Hospital its affiliated institutions between 2009 2024. Patients received chemotherapy as a (gemcitabine plus cisplatin or carboplatin), followed by second‐line inhibitors (pembrolizumab avelumab) third‐line Assessed overall time to failure. Cox regression analysis identified prognostic factors for survival. Results Over median follow‐up of 20.5 months, was not reached after treatment. Gemcitabine selected 31.6% cases, while gemcitabine carboplatin chosen 68.4% cases the treatment; subsequently, 66.7% pembrolizumab, 33.3% avelumab who achieved complete partial response had significantly longer survivals from both vedotin initiation than those stable progressive disease. In that responses, more frequently therapy. However, treatment, multivariate only disease significant predictor worse Conclusion The best predicted following underscoring value carcinoma.

Language: Английский

Citations

1
Nectin-4-directed antibody-drug conjugates (ADCs): Spotlight on preclinical and clinical evidence DOI

Mohammad Javad Khosravanian,

Yousef Mirzaei,

Ali Hussein Mer

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 352, P. 122910 - 122910

Published: Sept. 1, 2024

Language: Английский

Citations

7
Real world evidence of enfortumab vedotin in patients with advanced urothelial cancer: A multicenter observational study DOI
Wataru Fukuokaya, Yuhei Koike,

Yuji Yata

et al.

International Journal of Urology, Journal Year: 2023, Volume and Issue: 31(4), P. 342 - 347

Published: Dec. 19, 2023

Objectives To explore the characteristics of patients and assess effectiveness enfortumab vedotin (EV) in those with treatment‐resistant advanced urothelial cancer a real‐world setting. Patients Methods A multicenter observational study was conducted on 103 evaluable who received EV. Outcomes were assessed by radiographic response, progression‐free survival (PFS), overall (OS), treatment‐related adverse events (trAEs). Radiographic response using Response Evaluation Criteria Solid Tumors version 1.1, while trAEs studied line Common Terminology for Adverse Events 5.0. Results The median follow‐up 8.9 months (range, 0.1–16.4). observed objective rate 50.5%. PFS 6.0 (95% CI: 4.7–9.8), OS 14.5 12.4–not reached). Out patients, 19 (18.4%) had an Eastern Cooperative Oncology Group performance status 2 or more, 14 (14.7%) non‐urothelial carcinoma histology, 40 (38.3%) at least one pre‐existing comorbidity. There 26 (25.2%) reported 49 trAEs, 9 (18.3%) being grade 3 higher. most common included rash, occurring 18.4%. Conclusions This describes outcomes previously treated receiving findings demonstrate that EV showed robust anti‐tumor activity manageable safety profiles outside clinical trial

Language: Английский

Citations

16
Association between response to enfortumab vedotin and peripheral neuropathy in urothelial carcinoma patients: a multicenter retrospective study DOI

Nozomi Hayakawa,

Eiji Kikuchi, Go Kaneko

et al.

Japanese Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 54(11), P. 1194 - 1200

Published: June 14, 2024

Abstract Background Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The association between the occurrence of EV-related side effects and clinical outcome remains to be elucidated. Methods We identified 97 mUC treated EV at our five institutions from date approval March 2023. median follow-up period 7.0 months. retrospectively analyzed efficacy safety EV. Results age 71 years old, 39% had PS 1 or more, 56.7% primary tumor upper urinary tract. Overall response rate (ORR) therapy, progression-free survival (PFS), overall (OS) were 43.3%, 7.52 months, 12.78 respectively. Any grade treatment-related skin disorder, dysgeusia, peripheral neuropathy, gastrointestinal hyperglycemia occurred 61 (62.9%), 36 (37.1%), 34 (35.1%), 29 (29.9%), 18 (18.6%) patients, EV-associated neuropathy significantly higher ORR (58.8% vs. 34.9%, P = .032) longer PFS (8.05 6.31 .017) OS (not reached 11.57 .008, respectively) than those without. treatment presence peritoneal dissemination factors independently associated (hazard ratio 0.46, .008 hazard raito 3.83, .004, 0.30, .005 4.53, .002, respectively). Conclusions might patients.

Language: Английский

Citations

5