Update 8-1-2023

The mUC treatment algorithm has been updated based on the label change for pembrolizumab, the voluntary withdrawal of the atezolizumab indication, and the approval of pembrolizumab plus enfortumab vedotin for the treatment of patients with advanced mUC.

Updated mUC treatment algorithm

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC Urothelial Cancer Immunotherapy Guideline Expert Panel. More information on the SITC Guidelines can be found at sitcancer.org/guidelines.

Update 8-1-2023

Based on the voluntary withdrawal by the manufacturer of the atezolizumab indication for the treatment of cisplatin- and platinum-ineligible patients with mUC, the Urothelial Cancer CPG has been updated in the Diagnostic tests and biomarkers for urothelial cancer immunotherapy, Advanced/metastatic urothelial carcinoma, and the mUC treatment algorithm sections.

Based on the approval of nadofaragene firadenovec for the treatment of BCG-unresponsive NMIBC with CIS with or without papillary tumors, the Urothelial Cancer CPG has been updated in the Non-muscle invasive bladder cancer section.

Reference: [Nadofaragene firadenovec (Adstiladrin, Ferring Pharmaceuticals) FDA press release] (https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-high-risk-non-muscle-invasive-bladder-cancer)

Based on the approval of Enfortumab vedotin with pembrolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy, the Urothelial Cancer CPG has been updated in the Advanced/metastatic urothelial carcinoma and mUC treatment algorithm sections.

Reference: Pembrolizumab (Keytruda, Merck & Co, Inc) plus enfortumab vedotin (Padcev, Astellas Pharma) FDA press release

Update 8-24-2022

Based on the indication change for pembrolizumab for the treatment of patients with mUC, the Urothelial Cancer CPG has been updated in the following locations: - Immunotherapies for First-line Treatment of mUC - mUC Treatment Algorithm

Update 9-21-2021

Based on the approval of nivolumab for the treatment of patients with urothelial cancer who are at high risk of recurrence after undergoing radical resection, the Urothelial Cancer CPG has been updated in the following locations: - Phase III trials of adjuvant therapy for MIBC - Immunotherapy with chemoradiation as bladder-sparing therapy - Table 5 - mUC treatment algorithm - Immunotherapies for first-line treatment of mUC - Immunotherapies for R/R mUC

Reference: Nivolumab (Opdivo) FDA press release

Update 9-21-2021

Addition of information on the approval of nivolumab as adjuvant treatment for patients with surgically resected, high-risk MIBC, as noted below:

• The FDA granted priority review status to the Biologics License Application for nivolumab for adjuvant treatment of patients with surgically resected, high-risk MIBC in April 2021, and subsequently approved nivolumab for the treatment of patients with urothelial cancer (UC) who are at high risk of recurrence after undergoing radical resection in August 2021.

Update 9-21-2021

Recommendation modified to include information on the approval of nivolumab as adjuvant treatment for patients with surgically resected, high-risk MIBC, as noted below:

• For patients with MIBC at high risk for recurrence after radical resection (ypT2-ypT4a or ypN+ for patients who received neoadjuvant cisplatin-based chemotherapy or pT3-pT4a or pN+ for patients who did not receive neoadjuvant cisplatin-based chemotherapy and who also either were ineligible for or refused adjuvant cisplatin-based chemotherapy) adjuvant nivolumab extends DFS as demonstrated in CheckMate 274 (LE: 2). Neoadjuvant therapy with cisplatin-based combination chemotherapy remains the treatment paradigm for curative intent therapy when surgery is considered; the data of CheckMate 274 are insufficient to conclude that adjuvant immunotherapy alone can replace the current practice which is known to maximize survival. Active investigation is ongoing into various additional neoadjuvant and/or adjuvant strategies (and bladder preservation), either as single agents, or in combination with chemotherapy, radiotherapy, or novel agents.

Update 8-24-2022

Modification below reflects the indication change for pembrolizumab for the first-line treatment of patients with mUC:

• …in May 2017, the FDA approved pembrolizumab for use as a first-line treatment of mUC in any patient ineligible for platinum-based chemotherapy regardless of PD-L1 status.

Update 9-21-2021

At the conclusion of this sentence, the modification below is added to include information on the approval of nivolumab as adjuvant treatment for patients with surgically resected, high-risk MIBC.

• Full approval of nivolumab in this setting was granted in August, 2021.