Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial

Szabados, Bernadett; Rodríguez‐Vida, Alejo; Durán, Ignacio; Crabb, Simon J.; Heijden, Michiel S. van der; Pous, Albert Font; Gravis, Gwénaëlle; Herranz, Urbano Anido; Protheroe, Andrew; Ravaud, Alain; Maillet, Denis; Mendez-Vidal, María José; Suárez, Cristina; Linch, Mark; Prendergast, Aaron; Tyson, Charlotte; Mousa, Kelly; Castellano, Daniel; Schmid, Peter

doi:10.1016/j.euo.2020.11.010

Cited by 19 publications

(14 citation statements)

References 28 publications

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“…Globally, early-phase trials have shown that neoadjuvant ICIs prior to surgery were well tolerated, with the majority proceeding to radical cystectomy with no delay. Importantly, up to 14% of patients may experience retarded immune-related AEs after cystectomy, as shown recently in an updated analysis of ABACUS, including adrenal insufficiency, hypothyroidism, and an increase in liver enzymes [ 12 ]. Thus, monitoring patients for these toxicities is mandatory.…”

Section: Resultsmentioning

confidence: 99%

Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer

et al. 2021

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Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative immunotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.

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Section: Resultsmentioning

confidence: 99%

Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer

et al. 2021

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“…The need to stratify muscle-invasive UC into subtypes that require different systemic treatment approaches will become ever more important following the introduction of checkpoint inhibitors in the neoadjuvant setting 34 and new third line regimens for those patients who progress after chemotherapy and checkpoint inhibitors. [35][36][37] Based on our results, and the fact that no previous biomarker has reached clinical use, we propose that results in this space may improve with the identification of second generation biomarkers, i.e.…”

Section: Discussionmentioning

confidence: 99%

Different responses to neoadjuvant chemotherapy in urothelial carcinoma molecular subtypes

Sjödahl

Abrahamsson

Holmsten

et al. 2021

Preprint

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For muscle-invasive bladder cancer (MIBC), there are no tissue biomarkers in clinical use that identify patients sensitive or resistant to neoadjuvant chemotherapy. The present study investigates how molecular subtypes impact pathological response and survival in 149 patients receiving preoperative cisplatin-based chemotherapy. Tumor classification was performed by transcriptomic profiling and by a 13-marker immunostaining panel. Furthermore, we explored differential gene expression and chemotherapy response beyond molecular subtypes. Tumors with Genomically Unstable (GU) and Urothelial-like (Uro) subtypes had higher proportions of pathological response and superior survival outcomes as compared to the Basal-Squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Based on our findings, we suggest that urothelial cancer of the luminal-like GU- and Uro-subtypes are more responsive to cisplatin-based chemotherapy. We also found the gene coding for osteopontin (SPP1) to display a subtype-dependent effect on chemotherapy response, confirmed at the protein level by immunohistochemistry. Combined analyses of second-generation, subtype-specific biomarkers may be an additional way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.

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“…In the ABACUS trial by Powles et al, 95 patients with MIBC treated with two cycles of atezolizumab before cystectomy had a pathological CRR of 31% (95% CI: 21-41%) [124]. According to the result of the updated safety analysis of the ABACUS trial reported by Szabados et al, the common adverse effects were fatigue (20%), decreased appetite (6%), and transaminitis (6%) [125]. A phase 1 trial study by Marcq et al suggests that considerable caution with atezolizumab for MIBC should be considered [126].…”

Section: Anti-pd-1/pd-l1 Icismentioning

confidence: 99%

Advances in Diagnosis and Therapy for Bladder Cancer

2022

Cancers

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Bladder cancer (BCa) is one of the most common and expensive urinary system malignancies for its high recurrence and progression rate. In recent years, immense amounts of studies have been carried out to bring a more comprehensive cognition and numerous promising clinic approaches for BCa therapy. The development of innovative enhanced cystoscopy techniques (optical techniques, imaging systems) and tumor biomarkers-based non-invasive urine screening (DNA methylation-based urine test) would dramatically improve the accuracy of tumor detection, reducing the risk of recurrence and progression of BCa. Moreover, intravesical instillation and systemic therapeutic strategies (cocktail therapy, immunotherapy, vaccine therapy, targeted therapy) also provide plentiful measures to break the predicament of BCa. Several exploratory clinical studies, including novel surgical approaches, pharmaceutical compositions, and bladder preservation techniques, emerged continually, which are supposed to be promising candidates for BCa clinical treatment. Here, recent advances and prospects of diagnosis, intravesical or systemic treatment, and novel drug delivery systems for BCa therapy are reviewed in this paper.

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Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial

Cited by 19 publications

References 28 publications

Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer

Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer

Different responses to neoadjuvant chemotherapy in urothelial carcinoma molecular subtypes

Advances in Diagnosis and Therapy for Bladder Cancer

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