Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma

Gao, Jianjun; Navai, Neema; Alhalabi, Omar; Siefker‐Radtke, Arlene O.; Campbell, Matthew T.; Tidwell, Rebecca S. Slack; Guo, Charles C.; Kamat, Ashish M.; Matin, Surena F.; Araujo, John C.; Shah, Amishi Yogesh; Msaouel, Pavlos; Corn, Paul G.; Wang, Jianbo; Papadopoulos, John; Yadav, Shalini S.; Blando, Jorge; Duan, Fei; Basu, Sreyashi; Liu, Wenbin; Shen, Yu; Zhang, Yuwei; Macaluso, Marc; Wang, Ying; Chen, Jianfeng; Zhang, Jianhua; Futreal, Andrew; Dinney, Colin P.; Allison, James P.; Goswami, Sangeeta; Sharma, Padmanee

doi:10.1038/s41591-020-1086-y

Cited by 233 publications

(164 citation statements)

References 55 publications

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“…Recently, phase II trials evaluating neoadjuvant ICB as a monotherapy or a combination therapy in patients with MIBC have been reported [15,16,31,32]. Combination regimen including ICB plus chemotherapy has also been evaluated in the presurgical setting.…”

Section: Prospective Trials Evaluating Neoadjuvant Icb In Mibcmentioning

confidence: 99%

“…Gao and colleagues [31] evaluated the combination of neoadjuvant durvalumab plus tremelimumab in cisplatinineligible patients or those refusing cisplatin-based NAC (NCT02812420). These trials were designed to enroll two cohorts of patients.…”

Section: Efficacy Of Combined Icb In the Presurgical Settingmentioning

confidence: 99%

“…The success of immune checkpoint therapy in advanced UC, as well as the precedent of neoadjuvant approach toward conventional chemotherapy, has led to significant interest in exploring the potential role of neoadjuvant ICB in MIBC [14]. Recently, early-phase clinical trials have reported the first results of neoadjuvant ICB alone or in combination before radical cystectomy in patients with resectable bladder cancer [15,16,31,32]. In the preclinical space, several important studies have highlighted the potential of neoadjuvant ICB in improving long-term survival in experimental bladder cancer models [17].…”

Section: Introductionmentioning

confidence: 99%

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Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Rouanne

Bajorin

Hannan

et al. 2020

European Urology Oncology

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Section: Prospective Trials Evaluating Neoadjuvant Icb In Mibcmentioning

confidence: 99%

Section: Efficacy Of Combined Icb In the Presurgical Settingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Rouanne

Bajorin

Hannan

et al. 2020

European Urology Oncology

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“…Intravesical chemotherapy and immunotherapy have demonstrated significant benefit in delaying disease recurrence in patients with NMIBC 4 . In MIBC patients, neoadjuvant chemotherapy with platinum-based drugs has been offered prior to local definitive treatment and has been associated with lower rates of recurrence and survival benefits 5,6 . Recently, a myriad of clinical trials has been launched to investigate the efficacy of immune checkpoint inhibitors combined with neoadjuvant therapy 7,8,9 .…”

Section: Introductionmentioning

confidence: 99%

“…The outcome of these clinical trials may significantly change the therapeutic landscape of MIBC patients as half of MIBC patients are not eligible to receive platinum-based neoadjuvant chemotherapy 10 . In patients receiving treatment with neoadjuvant therapy, pathological complete response (pCR, pT0N0) rates have been observed in 20% to 50% of cases 6,7,9 . While there is still room to develop more effective neoadjuvant therapies and increase pCR rates, avoiding surgery in bladder cancer patients who completely respond to neoadjuvant therapy is a continuing challenge faced by many urologic oncologists.…”

Section: Introductionmentioning

confidence: 99%

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash is Another Man’s Treasure

Minkler¹,

Lucien²,

Kimber³

et al. 2020

Preprint

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Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years1. Due to high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. There is, therefore, a critical need to develop innovative molecular and cellular tools to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.

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Immunotherapy in the Treatment of Localized Genitourinary Cancers

et al. 2023

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ImportanceA true revolution in the management of advanced genitourinary cancers has occurred with the discovery and adoption of immunotherapy (IO). The therapeutic benefits of IO were recently observed not to be solely confined to patients with disseminated disease but also in select patients with localized and locally advanced genitourinary neoplasms.ObservationsKEYNOTE-057 demonstrated the benefit of pembrolizumab monotherapy for treating high-risk nonmuscle invasive bladder cancer unresponsive to bacillus Calmette-Guérin (BCG), resulting in recent US Food and Drug Administration approval. Furthermore, a current phase 3 trial (Checkmate274) demonstrated a disease-free survival benefit with the administration of adjuvant nivolumab vs placebo in muscle-invasive urothelial carcinoma after radical cystectomy. In addition, the recent highly publicized phase 3 KEYNOTE 564 trial demonstrated a recurrence-free survival benefit of adjuvant pembrolizumab in patients with high-risk localized/locally advanced kidney cancer.Conclusions and RelevanceThe adoption and integration of IO in the management of localized genitourinary cancers exhibiting aggressive phenotypes are becoming an emerging therapeutic paradigm. Clinical oncologists and scientists should become familiar with these trials and indications because they are likely to dramatically change our treatment strategies in the months and years to come.

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Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma

Cited by 233 publications

References 55 publications

Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash is Another Man’s Treasure

Immunotherapy in the Treatment of Localized Genitourinary Cancers

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