Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma

Bajorin, Dean F.; Witjes, J. Alfred; Gschwend, Jürgen E.; Schenker, Michael; Valderrama, Begoña P.; Tomita, Yoshihiko; Bamias, Aristotelis; Lebrét, Thierry; Shariat, Shahrokh F.; Park, Se Hoon; Ye, Dingwei; Agerbæk, Mads; Enting, Deborah; McDermott, Ray; Gajate, Pablo; Peer, Avivit; Milowsky, Matthew I.; Носов, А. К.; Antonio, João Neif; Tupikowski, Krzysztof; Toms, Laurence; Fischer, Bruce S.; Qureshi, Anila; Collette, Sandra; Ünsal-Kaçmaz, Keziban; Broughton, Edward; Zardavas, Dimitrios; Koon, Henry; Galsky, Matthew D.

doi:10.1056/nejmoa2034442

Cited by 598 publications

(452 citation statements)

References 29 publications

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“…0.34-0.84). Grade 3 or 4 treatment-related adverse events occurred in 17.9% and 7.2% of patients in the nivolumab and placebo arms, respectively ( 43 ).…”

Section: Therapeutic Agents For Advanced or Metastatic Urothelial Carcinomamentioning

confidence: 99%

Elucidation of Novel Molecular Targets for Therapeutic Strategies in Urothelial Carcinoma: A Literature Review

2021

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Urothelial carcinoma therapy is a rapidly evolving and expanding field. Traditional cytotoxic chemotherapy regimens have not produced optimal long-term outcomes, and many urothelial cancer patients have comorbidities that disqualify them as chemotherapy candidates. In recent years, a plethora of novel therapeutic agents that target diverse molecular pathways has emerged as alternative treatment modalities for not only metastatic urothelial carcinoma, but also for muscle-invasive bladder cancer and non-muscle invasive bladder cancer in adjuvant and definitive settings. This review paper aims to discuss the various categories of therapeutic agents for these different types of urothelial cancer, discussing immunotherapy, antibody-drug conjugates, kinase inhibitors, CAR-T cell therapy, peptide vaccination, and other drugs targeting pathways such as angiogenesis, DNA synthesis, mTOR/PI3K/AKT, and EGFR/HER-2.

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“…0.34-0.84). Grade 3 or 4 treatment-related adverse events occurred in 17.9% and 7.2% of patients in the nivolumab and placebo arms, respectively ( 43 ).…”

Section: Therapeutic Agents For Advanced or Metastatic Urothelial Carcinomamentioning

confidence: 99%

Elucidation of Novel Molecular Targets for Therapeutic Strategies in Urothelial Carcinoma: A Literature Review

2021

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“…For the UTUC subgroup, the HR for disease recurrence or death were 1.23 (CI 95% 0.67-2.23) and 1.56 (CI 95% 0.7-3.48) for UTUC arising in renal pelvis and ureter, respectively. The percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; p < 0.001), for those expressing PD-L1 more than 1% [62]. Moreover, several neoadjuvant trials combining chemotherapy with ICI are actively recruiting, but available data are currently limited [63][64][65].…”

Section: Immune Checkpoint Inhibitors In the Perioperative Settingmentioning

confidence: 99%

Efficacy of Immune Checkpoint Inhibitors in Upper Tract Urothelial Carcinomas: Current Knowledge and Future Directions

Thouvenin

Chanzá

Alhalabi

et al. 2021

Cancers

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Upper tract urothelial carcinoma (UTUC) represents a rare and aggressive malignancy arising from the renal pelvis or ureter. It can develop sporadically or have a hereditary origin, such as Lynch syndrome, caused by DNA mismatch repair deficiency, leading to microsatellite instability phenotype. According to molecular characterization studies, UTUC presents different mutational profiles as compared to urinary bladder urothelial carcinomas. In particular, it has been reported that UTUC harbored a higher level of FGFR3 alterations associated with a T-cell depleted immune microenvironment. The therapeutic landscape in urothelial carcinoma is rapidly evolving, with immune checkpoint inhibitors forming part of the standard of care. A greater understanding of the molecular alterations and immune microenvironment leads to the development of new treatment combinations and targeted therapy. This review summarizes the available evidence concerning the use of immune checkpoint inhibitors and the biological rationale underlying their use in high-grade UTUC.

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“…In the adjuvant setting, the CheckMate 274 trial investigated the role of nivolumab in the treatment of MIBC following cystectomy, in both patients with prior neoadjuvant cisplatin-based chemotherapy and those without NAC and ineligible for adjuvant treatment [54]. Treatment with nivolumab compared to placebo resulted in a significantly longer median DFS, the primary endpoint, in the intent-to-treat (ITT) population (21.0 vs. 10.9 months, HR=0.70 [98.31% CI 0.54-0.89]; P<0.001), as well as in a subset of patients with PD-L1 expression ≥1% (not reached vs. 10.8 months, HR=0.53 [98.87% CI 0.34-0.84]; P<0.001).…”

Section: B2b: Bladder Cancer Summarymentioning

confidence: 99%

“…After the patient refused NAC, he underwent radical cystectomy and recovered well after surgery. Results of CheckMate 274 trial suggest that this patient could benefit from adjuvant treatment with nivolumab [54], which is not yet approved in this setting. Two weeks after receiving the first dose of nivolumab, the patient reported feeling unwell.…”

Section: B2b: Bladder Cancer Summarymentioning

confidence: 99%