Research ArticleClinical Studies
Open Access

Survival and Safety Outcomes of Avelumab Maintenance Therapy for Advanced Urothelial Carcinoma from a Single-Center Experience

AKINORI MINATO, YUI MIZUSHIMA, YOSHIHIRO SUGITA, TOMOHISA TAKABA, TAKUO MATSUKAWA, KAZUMASA JOJIMA, RIEKO KIMURO, KATSUYOSHI HIGASHIJIMA, YUJIRO NAGATA, IKKO TOMISAKI, EIJI KASHIWAGI and NAOHIRO FUJIMOTO
In Vivo July 2025, 39 (4) 2123-2132; DOI: https://doi.org/10.21873/invivo.14008

Abstract

Background/Aim: Avelumab maintenance therapy following first-line platinum-based chemotherapy is reportedly effective against advanced urothelial carcinoma (UC). However, this therapy, including its survival outcome, remains poorly investigated in a real-world setting in Japan.

Patients and Methods: This study retrospectively evaluated the clinical outcomes of avelumab maintenance therapy in patients with advanced lower- and upper-tract UC after no progression on first-line platinum-based chemotherapy at our institution between May 2021 and August 2024. Efficacy, survival, and safety analyses were performed starting from avelumab introduction.

Results: In total, 22 patients were enrolled, of which 7 (31.8%) were female, 9 (40.9%) had performance status score ≥1, and 9 (40.9%) had upper-tract UC. The objective response and disease control rates were 4.5% and 50.0%, respectively. While receiving avelumab, no patients experienced immune-related adverse events (irAEs) of grade ≥3. The median progression-free survival (PFS) and overall survival were 3.3 and 22.2 months, respectively. When comparing median PFS of patients with a complete or partial response to prior platinum-based chemotherapy to the patients with stable disease, the first had significantly longer PFS (4.0 months, 95% confidence interval=2.3-10.1 vs. 2.2 months, 95% confidence interval=0.9-3.9; p=0.034). The PFS did not significantly differ between patients with and without irAEs or infusion-related reaction.

Conclusion: Avelumab maintenance therapy demonstrated favorable survival outcomes and tolerability in patients with advanced UC in daily practice.

Keywords:

Introduction

Advanced (unresectable/metastatic) urothelial carcinoma (UC) is generally progressive. Conventionally, its first-line treatment is platinum-based chemotherapy. Although the disease control rate is 63.7%-82% (1-3), the high responsiveness to platinum-based chemotherapy alone cannot be maintained for long. Therefore, the median overall survival (OS) of patients with advanced UC who have received first-line chemotherapy is insufficient (13.2-15.2 months) (1-3).

Since 2017, three immune checkpoint inhibitors (ICIs), namely, pembrolizumab, avelumab, and nivolumab, have been successively introduced, depending on the timing of treatment in Japan, according to the results of large randomized phase 3 trials (4-6). In the JAVELIN Bladder 100 trial, avelumab, a programmed cell death-ligand 1 (PD-L1) inhibitor, was administered as a maintenance therapy after 4-6 cycles of first-line platinum-based chemotherapy, and it achieved an OS of 21.4 months (5). If the response to prior chemotherapy is more than a stable disease (SD), avelumab maintenance therapy has proven to significantly prolong survival compared to the best supportive care (BSC). Additionally, enfortumab vedotin (EV) monotherapy, an antibody-drug conjugate directed against nectin-4, was approved as a late-line treatment after platinum-based chemotherapy and subsequent ICI therapy failure, as reported in the EV-301 trial conducted in 2021 (7).

Over 3 years from the time of avelumab approval, avelumab maintenance therapy has become a standard of care for advanced UC in daily clinical practice. However, in Japan, the real-world data regarding avelumab treatment against advanced UC remains insufficiently investigated (8-11). Moreover, prognostic factors in the novel maintenance therapy era are not well characterized.

Hence, this research aimed to evaluate the efficacy, safety, and survival outcomes of avelumab maintenance therapy in patients without progression after receiving first-line platinum-based chemotherapy. These patients participated in the single-center, retrospective observational study.

Patients and Methods

Patient population. This retrospective study protocol obtained approval from the University of Occupational and Environmental Health Institutional Review Board (approval no.: UOEHCRB21-048) and conformed to the principles of the Declaration of Helsinki. Owing to retrospective nature of the study, individual consent for participation in this analysis was waived, but an opt-out option was provided through the websites of our homepage. Using the single-center population, we identified 40 consecutive patients with advanced UC (unresectable or metastatic) who were introduced first-line platinum-based chemotherapy. After the radiological confirmation of the absence of disease progression following the first-line chemotherapy, 22 patients with SD, partial response (PR), and complete response (CR) switched to avelumab maintenance therapy between May 2021 and August 2024.

Patient management and evaluation. Avelumab (10 mg/kg) was administered intravenously every 14 days until either of the following occurred: confirmed disease progression, unacceptable adverse events (AEs), or consent withdrawal. For imaging evaluation, computed tomography was conducted at baseline and after every 4-6 cycles of avelumab treatment or as clinically necessary (9).

The best response to avelumab was categorized according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (12). The overall response rate (ORR) was the proportion of patients with CR or PR. Additionally, in the analysis of avelumab maintenance therapy, a CR to platinum-based chemotherapy but no evidence of the disease during avelumab efficacy evaluation was considered as “could not be evaluated” (NE) (8). Therefore, the disease control rate was defined as the proportion of patients with CR, PR, SD, and NE.

Drug safety was analyzed according to the Common Terminology Criteria for Adverse Events version 5.0 (13) to summarize the frequency of treatment-related AEs. Additionally, we did not categorize infusion-related reaction (IRR) as an immune-related AE (irAE), which is in line with the JAVELIN Bladder 100 trial (5).

Statistical analysis. Statistical data were analyzed using EZR version 1.55 (Easy R, Saitama Medical Center, Jichi Medical University, Saitama, Japan) (14). Categorical data are presented as counts and percentages, while continuous data as median (range) or median [interquartile range (IQR)]. Between-group differences were assessed using Fisher’s exact test for categorical variables and Mann-Whitney U-test for continuous variables. Progression-free survival (PFS) was assessed from the date of avelumab treatment initiation until the date of disease progression or death, whichever happened first, or until the last follow-up of patients without disease progression. OS was assessed from the date of avelumab treatment initiation until the date of death for any reason or until the last follow-up of patients who survived. OS and PFS were calculated using the Kaplan-Meier method and compared using the logrank test. A p-value <0.05 was considered statistically significant.

Results

Patient characteristics. A total of 22 patients were confirmed without disease progression in the response to first-line platinum-based chemotherapy and were included in the study. Table I shows the baseline characteristics of the participants who received avelumab maintenance therapy. Overall, the median age was 72 years, and 7 (31.8%) of them were female. Nine (40.9%) had Eastern Cooperative Oncology Group performance status score ≥1, and 9 (40.9%) had upper-tract UC. Half of patients received a cisplatin-based regimen as first-line treatment and, approximately 45.5% were treated with the carboplatin-based regimen. The patients received a median of 4 cycles (range=4-9) of first-line chemotherapy. Regarding the response to first-line chemotherapy, 14 (63.6%) patients had CR and PR, and 8 (36.4%) had SD. As for the metastatic site at treatment initiation, 8 (36.4%) were in the lymph node-only disease, whereas 10 (45.5%) had visceral metastasis.

View this table:
Table I.

Baseline characteristics.

Oncological outcomes. The ORR and disease control rates of the 22 patients receiving avelumab maintenance therapy were 4.5% and 50.0%, respectively (Table II). During the analysis (November 2024), 2 (9.1%) patients were still on avelumab maintenance treatment. Moreover, 2 (9.1%) patients had withdrawal of avelumab due to AEs. After avelumab discontinuation, 19 (86.3%) patients received subsequent pharmacotherapy, which included EV monotherapy (81.8%) and platinum-based chemotherapy (4.5%). Only one patient had the BSC.

View this table:
Table II.

Results of response and outcomes to avelumab maintenance therapy.

The median follow-up period from avelumab introduction was 18.0 months (IQR=9.7-31.5 months), during which 20 (91.0%) patients experienced radiological progression and 10 (40.5%) died. The median PFS and OS were 3.3 and 22.2 months [95% confidence interval (CI)=2.0-4.7 and 15.9–not estimable], respectively (Figure 1). Figure 2 shows the post–avelumab therapy PFS of patients stratified by the type of prior platinum agent (cisplatin or carboplatin), number of platinum-based chemotherapy cycles (cutoff value of 4 cycles), and the response to prior platinum-based chemotherapy (CR/PR or SD). The median PFS was 4.0 months (95% CI=2.3-10.1) in patients with CR or PR and 2.2 months (95% CI=0.9-3.9) in those with SD (p=0.034, Figure 2C). Figure 3 presents PFS after initiation of avelumab maintenance in patients stratified according to the disease site. The median PFS was 4.4 months (95% CI=1.2–not estimable) in patients with only lymph node metastasis (Figure 3B), and 3.1 months (95% CI=1.2-4.0) in those with visceral metastasis (Figure 3C).

Figure 1.
Figure 1.

Survival curves of the study population. Progression-free survival (A) and overall survival (B) after the initiation of avelumab maintenance therapy in patients with advanced urothelial carcinoma.

Figure 2.
Figure 2.

Progression-free survival (PFS) after the initiation of avelumab maintenance therapy. PFS of the patients with advanced urothelial carcinoma stratified according to the type of platinum agent (A), number of treatment cycles (B), and best response to the first-line chemotherapy (C). Survival curves were compared using logrank test. SD: Stable disease; CR: complete response; PR: partial response.

Figure 3.
Figure 3.

Progression-free survival after the initiation of avelumab maintenance therapy stratified according to the disease site and metastasis status. Bladder or upper urinary tract (A), lymph node-only metastasis or other metastases (B), and visceral or nonvisceral metastasis (C). Survival curves were compared using logrank test.

Toxicity. As shown in Table III, the most common AE and irAE were IRR and skin toxicity. Among the studied patients, six (27.3%) had an IRR, including one (4.5%) with a grade 4 event. The occurrence of irAEs of grade ≥3 was 0%. Although two (9.1%) patients discontinued avelumab because of IRR and hepatobiliary disorder, none led to death caused by treatment-related AEs. The PFS did not significantly differ between patients with and without irAEs or IRRs (Figure 4).

View this table:
Table III.

Treatment-related adverse events of avelumab.

Figure 4.
Figure 4.

Progression-free survival after the initiation of avelumab maintenance therapy according to the occurrence of immune-related adverse event (A) and infusion-related reaction (B). Survival curves were compared using logrank test. irAE: Immune-related adverse event; IRR: infusion-related reaction.

Discussion

To assess the survival outcomes of first-line maintenance therapy for advanced UC, this study retrospectively analyzed patients without disease progression who underwent avelumab maintenance therapy after receiving platinum-based chemotherapy. In this study, the median OS from avelumab therapy introduction was 22.2 months. We previously reported that the median OS after initiating of first-line platinum-based chemotherapy at a single institution (n=179) was 13.2 months (3). Additionally, in patients with disease control (CR, PR, and SD) receiving platinum-based chemotherapy, the OS did not significantly differ between patients receiving subsequent chemotherapy and those receiving BSC (3). Given that the efficacy of platinum-based chemotherapy cannot be maintained for a longer time, the durability of avelumab treatment is important. Considering the prognosis from the start of primary chemotherapy (approximately 14-15 months) in previous large randomized clinical trials (1, 2), our study suggested that the efficacy of avelumab maintenance could achieve a favorable survival outcome. Moreover, our survival outcome was similar to those from the JAVELIN Bladder 100 trial after ≥2 years of follow-up (median OS=23.8 months) (15).

In 2022 in Japan, Miyake et al. (8) were the first to show that avelumab maintenance therapy is clinically beneficial in terms of OS compared with second-line pembrolizumab and second-line chemotherapy in a retrospective multicenter study (n=27). Conversely, Shindo et al. (10) reported similar oncological outcomes between maintenance avelumab therapy (n=43) and second-line pembrolizumab therapy (n=43) in patients with advanced UC, after adjusting for patient characteristics. Recently, Kikuchi et al. in the multicenter, noninterventional, and retrospective medical chart review in Japan, J-AVENUE study (11), obtained a disease control rate of 58.2% and a median PFS of 6.1 months (n=79) but did not assess the OS duration because of the short observation period.

Given the lack of clinical reports in a real-world setting, no prognostic and effect predictors of avelumab maintenance therapy have been established. Furubayashi et al. (9) reported that an early experience of avelumab maintenance demonstrated no significant differences in OS between patients with and without metastasis to any organ (lymph node, lung, liver, and bone). In addition, the neutrophil-to-eosinophil ratio (NER) has been associated with survival in patients receiving avelumab maintenance therapy for advanced UC (16). At 6 weeks from avelumab initiation, the decreased NER group had significantly longer PFS and OS than the increased NER group on univariate analyses. Interestingly, our study revealed that the PFS from avelumab initiation significantly differed between patients with CR or PR to prior platinum-based chemotherapy and those with SD. In a multicenter retrospective study conducted in the US and Europe (n=108), patients with CR or PR to first-line platinum-based chemotherapy had a longer OS from avelumab introduction than those with SD (17). The SD category defines the reduction of target lesions and tumor growth of <20% (12). Therefore, the heterogeneity of responsiveness may affect the survival outcomes. Regarding other contributing factors, subgroup analyses from the JAVELIN Bladder 100 trial suggested that the survival benefit of avelumab was poor among females, patients with visceral metastasis, and upper-tract UC (18).

In this study, after discontinuing avelumab maintenance therapy, 81.8% of the patients subsequently received EV monotherapy. Since there were almost no cases that transitioned to BSC without subsequent pharmacotherapy, avelumab serves as a safe and effective connection. Moreover, we previously reported that EV monotherapy clearly contributed to patients’ prognosis in the late-line setting, with a median OS of 16.2 months from EV initiation (19). Currently, the sequential induction of platinum-based chemotherapy, avelumab maintenance therapy, and EV monotherapy is gradually expanding as a new treatment strategy against advanced UC (20-22). Most recently, patients receiving EV monotherapy after maintenance therapy could achieve long OS (>3 years) from the initiation of first-line chemotherapy (20, 22). Moreover, the advent of novel combination therapies, such as gemcitabine plus cisplatin with nivolumab and EV plus pembrolizumab, had a major impact on the pharmacotherapy scene for advanced UC (23, 24). Although these combination therapies are not yet widely used in Japan, the comparison of survival between such combination therapies and the sequential therapy (platinum-based chemotherapy, avelumab maintenance therapy, and EV monotherapy) will be required in the near future.

Compared with the previous clinical study population (5, 25), our patients had lower rates of discontinuation because of the irAEs of avelumab, but the incidence of IRR was higher. Although the association between ICI’s clinical benefit and irAEs was reported in various malignancies (26), the impact of avelumab efficacy on irAEs remains poorly understood. In fact, our study showed that irAE or IRR occurrence after avelumab induction was not associated with PFS. Moreover, the occurrence of irAEs of grade ≥3 was 0% and 7.0% in this study and the JAVELIN Bladder 100 trial, respectively (5). The low toxicity of avelumab may influence the association between efficacy and irAEs.

Our study has some limitations including its retrospective single-center design and the small sample size. The treatment cycles and type of first-line chemotherapy cycles were not uniform. In addition, the radiologic evaluation of avelumab was conducted by an investigator without central review. Given the limited number of patients in this cohort, we could not conduct a multivariate analysis to predict PFS and OS. Thus, further investigation is required with larger populations. Finally, the subsequent EV monotherapy may have strongly influenced the survival outcome after avelumab maintenance therapy failure.

Owing to the advent of the subsequent effective antibody-drug conjugate therapy (27, 28), the key role of avelumab is to connect the sequential therapy from platinum-based chemotherapy to EV monotherapy with high responsiveness. The results of our study support the importance of first-line maintenance therapy as a therapeutic strategy against advanced UC.

Conclusion

Avelumab as a maintenance therapy may improve the survival outcomes of patients with advanced UC, especially for those who have achieved the best response (CR/PR) to first-line platinum-based chemotherapy before avelumab introduction.

Acknowledgements

We would like to thank the late Dr. Kenichi Harada (Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan) for his advice and useful discussions.

Footnotes

  • Authors’ Contributions

    AM: Conceptualization, investigation, data curation, formal analysis, and writing of the original manuscript. YM and YS: Investigation and data curation. TT, TM, KJ, RK, KH, YN and IT: Data curation and reviewing of the manuscript. EK and NF: Supervision. All Authors discussed, verified, and approved the final version of the article.

  • Conflicts of Interest

    The Authors declare that they have no competing interests in relation to this study.

  • Received February 15, 2025.
  • Revision received March 17, 2025.
  • Accepted March 21, 2025.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

References

  1. ↵
    1. von der Maase H,
    2. Sengelov L,
    3. Roberts JT,
    4. Ricci S,
    5. Dogliotti L,
    6. Oliver T,
    7. Moore MJ,
    8. Zimmermann A,
    9. Arning M
    : Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23(21): 4602-4608, 2005. DOI: 10.1200/JCO.2005.07.757
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Dogliotti L,
    2. Cartenì G,
    3. Siena S,
    4. Bertetto O,
    5. Martoni A,
    6. Bono A,
    7. Amadori D,
    8. Onat H,
    9. Marini L
    : Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol 52(1): 134-141, 2007. DOI: 10.1016/j.eururo.2006.12.029
    OpenUrlCrossRefPubMed
  3. ↵
    1. Minato A,
    2. Ohno D,
    3. Murooka K,
    4. Okumura Y,
    5. Takaba T,
    6. Higashijima K,
    7. Nagata Y,
    8. Tomisaki I,
    9. Harada K,
    10. Fujimoto N
    : Optimal number of cycles of first-line platinum-based chemotherapy for metastatic urothelial carcinoma. In Vivo 38(4): 1927-1934, 2024. DOI: 10.21873/invivo.13648
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Bellmunt J,
    2. de Wit R,
    3. Vaughn DJ,
    4. Fradet Y,
    5. Lee JL,
    6. Fong L,
    7. Vogelzang NJ,
    8. Climent MA,
    9. Petrylak DP,
    10. Choueiri TK,
    11. Necchi A,
    12. Gerritsen W,
    13. Gurney H,
    14. Quinn DI,
    15. Culine S,
    16. Sternberg CN,
    17. Mai Y,
    18. Poehlein CH,
    19. Perini RF,
    20. Bajorin DF, KEYNOTE-045 Investigators
    : Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376(11): 1015-1026, 2017. DOI: 10.1056/NEJMoa1613683
    OpenUrlCrossRefPubMed
  5. ↵
    1. Powles T,
    2. Park SH,
    3. Voog E,
    4. Caserta C,
    5. Valderrama BP,
    6. Gurney H,
    7. Kalofonos H,
    8. Radulović S,
    9. Demey W,
    10. Ullén A,
    11. Loriot Y,
    12. Sridhar SS,
    13. Tsuchiya N,
    14. Kopyltsov E,
    15. Sternberg CN,
    16. Bellmunt J,
    17. Aragon-Ching JB,
    18. Petrylak DP,
    19. Laliberte R,
    20. Wang J,
    21. Huang B,
    22. Davis C,
    23. Fowst C,
    24. Costa N,
    25. Blake-Haskins JA,
    26. di Pietro A,
    27. Grivas P
    : Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med 383(13): 1218-1230, 2020. DOI: 10.1056/NEJMoa2002788
    OpenUrlCrossRefPubMed
  6. ↵
    1. Bajorin DF,
    2. Witjes JA,
    3. Gschwend JE,
    4. Schenker M,
    5. Valderrama BP,
    6. Tomita Y,
    7. Bamias A,
    8. Lebret T,
    9. Shariat SF,
    10. Park SH,
    11. Ye D,
    12. Agerbaek M,
    13. Enting D,
    14. McDermott R,
    15. Gajate P,
    16. Peer A,
    17. Milowsky MI,
    18. Nosov A,
    19. Neif Antonio J Jr.,
    20. Tupikowski K,
    21. Toms L,
    22. Fischer BS,
    23. Qureshi A,
    24. Collette S,
    25. Unsal-Kacmaz K,
    26. Broughton E,
    27. Zardavas D,
    28. Koon HB,
    29. Galsky MD
    : Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med 384(22): 2102-2114, 2021. DOI: 10.1056/NEJMoa2034442
    OpenUrlCrossRefPubMed
  7. ↵
    1. Powles T,
    2. Rosenberg JE,
    3. Sonpavde GP,
    4. Loriot Y,
    5. Durán I,
    6. Lee JL,
    7. Matsubara N,
    8. Vulsteke C,
    9. Castellano D,
    10. Wu C,
    11. Campbell M,
    12. Matsangou M,
    13. Petrylak DP
    : Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med 384(12): 1125-1135, 2021. DOI: 10.1056/NEJMoa2035807
    OpenUrlCrossRefPubMed
  8. ↵
    1. Miyake M,
    2. Shimizu T,
    3. Oda Y,
    4. Tachibana A,
    5. Ohmori C,
    6. Itami Y,
    7. Kiba K,
    8. Tomioka A,
    9. Yamamoto H,
    10. Ohnishi K,
    11. Nishimura N,
    12. Hori S,
    13. Morizawa Y,
    14. Gotoh D,
    15. Nakai Y,
    16. Torimoto K,
    17. Fujii T,
    18. Tanaka N,
    19. Fujimoto K
    : Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. Jpn J Clin Oncol 53(3): 253-262, 2023. DOI: 10.1093/jjco/hyac186
    OpenUrlCrossRefPubMed
  9. ↵
    1. Furubayashi N,
    2. Minato A,
    3. Tomoda T,
    4. Hori Y,
    5. Kiyoshima K,
    6. Negishi T,
    7. Haraguchi Y,
    8. Koga T,
    9. Kuroiwa K,
    10. Fujimoto N,
    11. Nakamura M
    : Organ-specific tumor response to avelumab maintenance therapy for advanced urothelial carcinoma: a multicenter retrospective study. Anticancer Res 43(12): 5689-5698, 2023. DOI: 10.21873/anticanres.16774
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Shindo T,
    2. Hashimoto K,
    3. Takahashi A,
    4. Miyamoto S,
    5. Kunishima Y,
    6. Sato S,
    7. Fukuta F,
    8. Hiyama Y,
    9. Takayanagi A,
    10. Kato R,
    11. Wanifuchi A,
    12. Ueki Y,
    13. Okada M,
    14. Adachi H,
    15. Kobayashi K,
    16. Tanaka T,
    17. Masumori N
    : Comparison of oncological outcomes of pembrolizumab as second-line therapy and maintenance avelumab therapy in advanced urothelial carcinoma after platinum-based chemotherapy. Anticancer Res 44(3): 1271-1279, 2024. DOI: 10.21873/anticanres.16922
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Kikuchi E,
    2. Hayakawa N,
    3. Nakayama M,
    4. Uno M,
    5. Nakatsu H,
    6. Kitagawa C,
    7. Miyake H,
    8. Yamada T,
    9. Fujita K,
    10. Shimoyama H,
    11. Nishihara K,
    12. Kobayashi M,
    13. Nakamura M,
    14. Fujimoto K,
    15. Sano T,
    16. Nishiyama N,
    17. Ito T,
    18. Kajita M,
    19. Kobayashi T,
    20. Kitamura H
    : J-AVENUE: A retrospective, real-world study evaluating patient characteristics and outcomes in patients with advanced urothelial carcinoma treated with avelumab first-line maintenance therapy in Japan. Int J Urol 31(8): 859-867, 2024. DOI: 10.1111/iju.15473
    OpenUrlCrossRefPubMed
  12. ↵
    1. Eisenhauer EA,
    2. Therasse P,
    3. Bogaerts J,
    4. Schwartz LH,
    5. Sargent D,
    6. Ford R,
    7. Dancey J,
    8. Arbuck S,
    9. Gwyther S,
    10. Mooney M,
    11. Rubinstein L,
    12. Shankar L,
    13. Dodd L,
    14. Kaplan R,
    15. Lacombe D,
    16. Verweij J
    : New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45(2): 228-247, 2009. DOI: 10.1016/j.ejca.2008.10.026
    OpenUrlCrossRefPubMed
  13. ↵
    1. National Institutes and Health, National Cancer Institute
    . Common Terminology Criteria for Adverse Events (CTCAE). v5.0., 2017. National Institute and Health. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf [Last accessed on Dec 29, 2024]
  14. ↵
    1. Kanda Y
    : Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3): 452-458, 2013. DOI: 10.1038/bmt.2012.244
    OpenUrlCrossRefPubMed
  15. ↵
    1. Powles T,
    2. Park SH,
    3. Caserta C,
    4. Valderrama BP,
    5. Gurney H,
    6. Ullén A,
    7. Loriot Y,
    8. Sridhar SS,
    9. Sternberg CN,
    10. Bellmunt J,
    11. Aragon-Ching JB,
    12. Wang J,
    13. Huang B,
    14. Laliberte RJ,
    15. di Pietro A,
    16. Grivas P
    : Avelumab first-line maintenance for advanced urothelial carcinoma: results from the JAVELIN Bladder 100 Trial after ≥2 years of follow-up. J Clin Oncol 41(19): 3486-3492, 2023. DOI: 10.1200/JCO.22.01792
    OpenUrlCrossRefPubMed
  16. ↵
    1. Furubayashi N,
    2. Minato A,
    3. Tomoda T,
    4. Hori Y,
    5. Kiyoshima K,
    6. Negishi T,
    7. Haraguchi Y,
    8. Koga T,
    9. Harada K,
    10. Kuroiwa K,
    11. Fujimoto N,
    12. Nakamura M, Uro-Oncology Group in Kyushu (UROKYU)
    : Change in the neutrophil-to-eosinophil ratio after avelumab maintenance for advanced urothelial carcinoma: the UROKYU study. Anticancer Res 44(4): 1675-1681, 2024. DOI: 10.21873/anticanres.16966
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. Bakaloudi DR,
    2. Talukder R,
    3. Lin GI,
    4. Makrakis D,
    5. Diamantopoulos LN,
    6. Tripathi N,
    7. Agarwal N,
    8. Zakopoulou R,
    9. Bamias A,
    10. Brown JR,
    11. Pinato DJ,
    12. Korolewicz J,
    13. Jindal T,
    14. Koshkin VS,
    15. Murgić J,
    16. Miletić M,
    17. Frobe A,
    18. Johnson J,
    19. Zakharia Y,
    20. Drakaki A,
    21. Rodriguez-Vida A,
    22. Rey-Cárdenas M,
    23. Castellano D,
    24. Buznego LA,
    25. Duran I,
    26. Carballeira CC,
    27. Barrera RM,
    28. Marmorejo D,
    29. McKay RR,
    30. Stewart T,
    31. Gupta S,
    32. Ruplin AT,
    33. Yu EY,
    34. Khaki AR,
    35. Grivas P
    : Response and outcomes of maintenance avelumab after platinum-based chemotherapy (PBC) in patients with advanced urothelial carcinoma (aUC): “Real world” experience. Clin Genitourin Cancer 21(5): 584-593, 2023. DOI: 10.1016/j.clgc.2023.06.008
    OpenUrlCrossRefPubMed
  18. ↵
    1. Grivas P,
    2. Park SH,
    3. Voog E,
    4. Caserta C,
    5. Gurney H,
    6. Bellmunt J,
    7. Kalofonos H,
    8. Ullén A,
    9. Loriot Y,
    10. Sridhar SS,
    11. Yamamoto Y,
    12. Petrylak DP,
    13. Sternberg CN,
    14. Gupta S,
    15. Huang B,
    16. Costa N,
    17. Laliberte RJ,
    18. di Pietro A,
    19. Valderrama BP,
    20. Powles T
    : Avelumab First-line maintenance therapy for advanced urothelial carcinoma: comprehensive clinical subgroup analyses from the JAVELIN bladder 100 phase 3 trial. Eur Urol 84(1): 95-108, 2023. DOI: 10.1016/j.eururo.2023.03.030
    OpenUrlCrossRefPubMed
  19. ↵
    1. Minato A,
    2. Furubayashi N,
    3. Tomoda T,
    4. Masaoka H,
    5. Song Y,
    6. Hori Y,
    7. Kiyoshima K,
    8. Negishi T,
    9. Kuroiwa K,
    10. Seki N,
    11. Tomisaki I,
    12. Harada K,
    13. Nakamura M,
    14. Fujimoto N
    : Organ-specific tumor response to enfortumab vedotin for metastatic urothelial carcinoma: a multicenter retrospective study. Clin Genitourin Cancer 22(5): 102148, 2024. DOI: 10.1016/j.clgc.2024.102148
    OpenUrlCrossRefPubMed
  20. ↵
    1. Barthelemy P,
    2. Loriot Y,
    3. Thibault C,
    4. Gross-goupil M,
    5. Eymard JC,
    6. Voog E,
    7. Abraham Jaillon C,
    8. Le Moulec S,
    9. Chasseray M,
    10. Gobert A,
    11. Auberger B,
    12. Viala C,
    13. Cabart M,
    14. Kazan E,
    15. Lorgis V,
    16. Hilgers W,
    17. Josse C,
    18. Lambert P,
    19. Solbes MN,
    20. Flechon A
    : Updated results from AVENANCE: Real-world effectiveness of avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) and analysis of subsequent treatment. J Clin Oncol 42(4_suppl): 561-561, 2024. DOI: 10.1200/JCO.2024.42.4_suppl.561
    OpenUrlCrossRef
    1. Nizam A,
    2. Jindal T,
    3. Jiang CY,
    4. Alhalabi O,
    5. Bakaloudi DR,
    6. Talukder R,
    7. Davidsohn MP,
    8. Nguyen CB,
    9. Oh E,
    10. Taylor AK,
    11. Lemke E,
    12. Kilari D,
    13. Hoimes CJ,
    14. Emamekhoo H,
    15. Gupta S,
    16. Bellmunt J,
    17. Grivas P,
    18. Campbell MT,
    19. Alva AS,
    20. Koshkin VS
    : Outcomes in patients (pts) with advanced urothelial carcinoma (aUC) treated with enfortumab vedotin (EV) after switch maintenance avelumab (MAv) in the UNITE study. J Clin Oncol 42(4_suppl): 537-537, 2024. DOI: 10.1200/JCO.2024.42.4_suppl.537
    OpenUrlCrossRef
  22. ↵
    1. Minato A,
    2. Furubayashi N,
    3. Tomoda T,
    4. Masaoka H,
    5. Song Y,
    6. Hori Y,
    7. Kiyoshima K,
    8. Negishi T,
    9. Kuroiwa K,
    10. Seki N,
    11. Tomisaki I,
    12. Nakamura M,
    13. Harada K,
    14. Fujimoto N
    : Clinical outcomes of enfortumab vedotin in advanced urothelial carcinoma with prior avelumab versus pembrolizumab therapy. Anticancer Res 44(8): 3419-3426, 2024. DOI: 10.21873/anticanres.17162
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. van der Heijden MS,
    2. Sonpavde G,
    3. Powles T,
    4. Necchi A,
    5. Burotto M,
    6. Schenker M,
    7. Sade JP,
    8. Bamias A,
    9. Beuzeboc P,
    10. Bedke J,
    11. Oldenburg J,
    12. Chatta G,
    13. Ürün Y,
    14. Ye D,
    15. He Z,
    16. Valderrama BP,
    17. Ku JH,
    18. Tomita Y,
    19. Filian J,
    20. Wang L,
    21. Purcea D,
    22. Patel MY,
    23. Nasroulah F,
    24. Galsky MD, CheckMate 901 Trial Investigators
    : Nivolumab plus gemcitabine–cisplatin in advanced urothelial carcinoma. N Engl J Med 389(19): 1778-1789, 2023. DOI: 10.1056/NEJMoa2309863
    OpenUrlCrossRefPubMed
  24. ↵
    1. Powles T,
    2. Valderrama BP,
    3. Gupta S,
    4. Bedke J,
    5. Kikuchi E,
    6. Hoffman-Censits J,
    7. Iyer G,
    8. Vulsteke C,
    9. Park SH,
    10. Shin SJ,
    11. Castellano D,
    12. Fornarini G,
    13. Li JR,
    14. Gümüş M,
    15. Mar N,
    16. Loriot Y,
    17. Fléchon A,
    18. Duran I,
    19. Drakaki A,
    20. Narayanan S,
    21. Yu X,
    22. Gorla S,
    23. Homet Moreno B,
    24. van der Heijden MS, EV-302 Trial Investigators
    : Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med 390(10): 875-888, 2024. DOI: 10.1056/NEJMoa2312117
    OpenUrlCrossRefPubMed
  25. ↵
    1. Tomita Y,
    2. Yamamoto Y,
    3. Tsuchiya N,
    4. Kanayama H,
    5. Eto M,
    6. Miyake H,
    7. Powles T,
    8. Yoshida M,
    9. Koide Y,
    10. Umeyama Y,
    11. di Pietro A,
    12. Uemura H
    : Avelumab first-line maintenance plus best supportive care (BSC) vs. BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis. Int J Clin Oncol 27(2): 383-395, 2022. DOI: 10.1007/s10147-021-02067-8
    OpenUrlCrossRefPubMed
  26. ↵
    1. Hussaini S,
    2. Chehade R,
    3. Boldt RG,
    4. Raphael J,
    5. Blanchette P,
    6. Maleki Vareki S,
    7. Fernandes R
    : Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors – A systematic review and meta-analysis. Cancer Treat Rev 92: 102134, 2021. DOI: 10.1016/j.ctrv.2020.102134
    OpenUrlCrossRefPubMed
  27. ↵
    1. Rosenberg JE,
    2. Powles T,
    3. Sonpavde GP,
    4. Loriot Y,
    5. Duran I,
    6. Lee JL,
    7. Matsubara N,
    8. Vulsteke C,
    9. Castellano D,
    10. Mamtani R,
    11. Wu C,
    12. Matsangou M,
    13. Campbell M,
    14. Petrylak DP
    : 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 34(11): 1047-1054, 2023. DOI: 10.1016/j.annonc.2023.08.016
    OpenUrlCrossRefPubMed
  28. ↵
    1. Loriot Y,
    2. Petrylak DP,
    3. Rezazadeh Kalebasty A,
    4. Fléchon A,
    5. Jain RK,
    6. Gupta S,
    7. Bupathi M,
    8. Beuzeboc P,
    9. Palmbos P,
    10. Balar AV,
    11. Kyriakopoulos CE,
    12. Pouessel D,
    13. Sternberg CN,
    14. Tonelli J,
    15. Sierecki M,
    16. Zhou H,
    17. Grivas P,
    18. Barthélémy P,
    19. Tagawa ST
    : 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: updated safety and efficacy outcomes. Ann Oncol 35(4): 392-401, 2024. DOI: 10.1016/j.annonc.2024.01.002
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Survival and Safety Outcomes of Avelumab Maintenance Therapy for Advanced Urothelial Carcinoma from a Single-Center Experience
AKINORI MINATO, YUI MIZUSHIMA, YOSHIHIRO SUGITA, TOMOHISA TAKABA, TAKUO MATSUKAWA, KAZUMASA JOJIMA, RIEKO KIMURO, KATSUYOSHI HIGASHIJIMA, YUJIRO NAGATA, IKKO TOMISAKI, EIJI KASHIWAGI, NAOHIRO FUJIMOTO
In Vivo Jul 2025, 39 (4) 2123-2132; DOI: 10.21873/invivo.14008
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords