First-in-human Intravesical Delivery of Pembrolizumab Identifies Immune Activation in Bladder Cancer Unresponsive to Bacillus Calmette-Guérin

Meghani, Khyati; Cooley, Lauren Folgosa; Choy, Bonnie; Kocherginsky, Masha; Swaminathan, Suchitra; Munir, Sabah S.; Svatek, Robert S.; Kuzel, Timothy M.; Meeks, Joshua J.

doi:10.1016/j.eururo.2022.08.004

Cited by 40 publications

(42 citation statements)

References 13 publications

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“…Meghani reported that intravesical pembrolizumab could be safe and feasible in BCa unresponsive to BCG, but with small sample size, further study needs to be performed. 36 …”

Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of Tislelizumab as Adjuvant Treatment for Advanced or Metastatic Bladder Cancer in People Living With HIV: A Retrospective Multi-Center Study

Zheng

Wang

et al. 2023

Cancer Control

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Background People living with HIV (PLWH) have a worse prognosis than the general population. Locally advanced or metastatic bladder cancer (BCa) in PLWH has gradually been increasing in recent years. Immune checkpoint inhibitors can improve antitumor activity in the general population, but relevant data in PLWH are unknown. We thus evaluated the efficacy and safety of tislelizumab in PLWH with locally advanced or metastatic BCa. Methods This retrospective study included 24 patients with locally advanced or metastatic BCa, both HIV positive or negative who underwent tislelizumab treatment (200 mg i.v. every 3 weeks, Q3W) from the multi-centers between December 2019 and March 2022. Demographic details, clinical data, and cancer status were collected. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and treatment-related adverse events (TRAEs) were recorded and evaluated. Results A total of 24 individuals were chosen for this study, 10 had HIV and the other 14 did not. The median OS in the HIV-negative group was 62.3 (95% CI, 52.6 to 72.2) was no longer than that of the PLWH group 41.9 (95% CI, 32.9 to 51.0) weeks (HR .7, [95% CI, .17 to 3.30], P = .70). Furthermore, the median PFS in the HIV-negative group was 50.0 (95% CI, 36.2 to 63.9) was also no longer than that of the PLWH group 35.9 (95% CI, 25.5 to 46.3) (HR, 1.34, [95% CI, .38 to 4.69], P = .63). Of 24 patients, treatment-related adverse events, grade 3 or 4 occurred in 2 in the PLWH group and 3 in the HIV-negative group. Conclusion This retrospective multi-center study suggested that tislelizumab may provide encouraging antitumor activity and could be generally well tolerated. In this retrospective analysis of patients with locally advanced or metastatic BCa, it seems that PLWH may have similar overall and progression-free survival compared to HIV-negative cases.

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“…Meghani reported that intravesical pembrolizumab could be safe and feasible in BCa unresponsive to BCG, but with small sample size, further study needs to be performed. 36 …”

Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of Tislelizumab as Adjuvant Treatment for Advanced or Metastatic Bladder Cancer in People Living With HIV: A Retrospective Multi-Center Study

Zheng

Wang

et al. 2023

Cancer Control

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“…Consequently, trials employing combination immunotherapy strategies have been deployed, some of which have demonstrated promising preliminary results . A recent phase 1 trial (n = 9) administered intravesical delivery of pembrolizumab and confirmed that this approach might represent a novel route of ICI administration that is safe and capable of eliciting a local immune response associated with therapeutic efficacy among patients with nonmuscle invasive disease, most notably in those patients meeting BCG unresponsive criteria …”

Section: Discussion/observationsmentioning

confidence: 99%

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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“…Intravesical administration of pembrolizumab was recently described in a phase 1 trial [ 19 ]. Meghani et al administered pembrolizumab in conjunction with BCG in nine patients with BCG-unresponsive disease.…”

Section: Immune Checkpoint Inhibitors (Pd-1/pd-l1 Inhibitors)mentioning

confidence: 99%

Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer

Awamlh

Chang

2022

Curr Oncol Rep

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Purpose of Review The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for high-risk NMIBC. Recent Findings Several therapies utilizing different mechanisms of action have demonstrated favorable results in the BCG-naïve and BCG-unresponsive settings. These treatments include intravenous and intravesical immunotherapy, viral- and bacterial-based intravesical therapies, combination intravesical chemotherapy regimens, and novel intravesical chemotherapy administration. Overall, the efficacy and tolerability of emerging treatments for NMIBC appear promising and provide potential alternatives to radical cystectomy. Summary As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives.

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First-in-human Intravesical Delivery of Pembrolizumab Identifies Immune Activation in Bladder Cancer Unresponsive to Bacillus Calmette-Guérin

Cited by 40 publications

References 13 publications

The Efficacy and Safety of Tislelizumab as Adjuvant Treatment for Advanced or Metastatic Bladder Cancer in People Living With HIV: A Retrospective Multi-Center Study

The Efficacy and Safety of Tislelizumab as Adjuvant Treatment for Advanced or Metastatic Bladder Cancer in People Living With HIV: A Retrospective Multi-Center Study

Immunotherapy in the Treatment of Localized Genitourinary Cancers

Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer

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