1059P NEMIO: A randomized phase I-II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma

Thibault, Constance; Elaidi, R.T.; Pouessel, Damien; Fléchon, Aude; Borchiellini, Delphine; Barthélémy, Philippe; Huillard, Olivier; Rouabah, M.; Braychenko, E.; Helali, I.; Audenet, François; Оудард, С.

doi:10.1016/j.annonc.2020.08.1179

Cited by 3 publications

(1 citation statement)

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“…NCT03549715 is a randomized phase II trial in which patients with MIBC received four cycles of neoadjuvant ddMVAC with two cycles of durvalumab alone or in combination with tremelimumab. 30 The primary endpoint in the 12 patient run-in phase, dose-limiting toxicity up to 3 months after cystectomy, was presented and indicated that the combination is safe. Other ongoing trials combining ddMVAC with ICI include NCT04383743 using pembrolizumab, NCT03674424 using avelumab, and RETAIN-2 (NCT04506554) using 32,33 Patients in the atezolizumab arm who cleared ctDNA had a superior DFS compared with those who remained positive for ctDNA (HR 0.26; 95% CI 0.12-0.56, p = 0.0014).…”

Section: Trials With Neoadjuvant Immunochemotherapy For Mibcmentioning

confidence: 99%

Role of immunotherapy in localized muscle invasive urothelial cancer

et al. 2021

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The standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy or trimodality therapy with chemoradiation in select patients. Pathologic complete response (pCR) to neoadjuvant chemotherapy is a reliable predictor of overall and disease-specific survival in MIBC. A pCR rate of 35–40% is attained with neoadjuvant cisplatin-based chemotherapy. With the approval of immune checkpoint inhibitors (ICIs) for the treatment of metastatic urothelial cancer, these agents are now being studied in the neoadjuvant setting for MIBC. We describe the results from clinical trials using single agent ICI, ICI/ICI and ICI/chemotherapy combination therapies in the neoadjuvant setting for MIBC. These single-arm clinical trials have demonstrated safety and pCR comparable to cisplatin-based chemotherapy. Neoadjuvant ICI is a promising approach for cisplatin-ineligible patients, and the role of adding ICIs to cisplatin-based chemotherapy is also being investigated in randomized phase III clinical trials. Ongoing biomarker research to suggest a response to neoadjuvant ICIs will also guide appropriate treatment selection. We also describe the studies using ICIs for adjuvant therapy and in combination with chemoradiation.

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Section: Trials With Neoadjuvant Immunochemotherapy For Mibcmentioning

confidence: 99%

Role of immunotherapy in localized muscle invasive urothelial cancer

et al. 2021

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Neoadjuvant Immunochemotherapy in the Treatment of Nonmetastatic Muscle-Invasive Bladder Cancer: A Systematic Review

et al. 2022

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Introduction: Multiple trials are currently studying the additional effect of immunotherapy on neoadjuvant chemotherapy (NAC) in nonmetastatic muscle-invasive bladder cancer. Methods: We performed a systematic review of the literature that summarizes all ongoing trials, with their results when available. Results: From an initial 269 trials identified, 17 were included. Pathological response and pathological complete response rates of the immunotherapy + NAC combination in the cisplatin-eligible population varied between 56.6–75% and 34.0–66.7%, respectively. Two studies published their results in the cisplatin-ineligible population, with pathological complete response rates of 18 and 45.2%. Conclusion: Neoadjuvant immunochemotherapy in platinum-eligible patients results in response rates higher than those reported for NAC alone. Strong preliminary results are still lacking in the platinum-ineligible population.

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Neoadjuvant immunotherapy and chemoimmunotherapy for stage II-III muscle invasive bladder cancer

et al. 2022

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ObjectiveConsidering the striking evidence revealed by immunotherapy in advanced or metastatic bladder cancer, investigators have explored neoadjuvant immunotherapy and chemoimmunotherapy in muscle-invasive bladder cancer (MIBC). Currently, there have been a large number of studies reporting varied efficacy and safety of these approaches. Herein, we pooled the available evidence in terms of oncological outcomes (pathological complete response [pCR] and pathological partial response [pPR]) and safety outcomes (immune-related adverse events [irAEs], treatment-related adverse events [TRAEs]), through a systematic review and meta-analysis.MethodWe searched PubMed, Embase, Cochrane Library, and American Society of Clinical Oncology meeting abstracts to identify relevant studies up to June 2022. Studies were included if they evaluated the neoadjuvant immunotherapy or chemoimmunotherapy in MIBC and reported at least the pCR.ResultsA total of 22 records involving 843 patients were included. For pCR of immunotherapy, the pooled rate of immune checkpoint inhibitor (ICI) monotherapy and dual-ICIs therapy was 24% (95% confidence interval [CI]: 15.3% - 32.8%) and 32.1% (95%CI: 20.6% - 43.7%), respectively. For pCR of chemoimmunotherapy, the overall pooled rate was 42.6% (95% CI: 34.9% - 50.2%). Subgroup of gemcitabine/cisplatin (GC) plus ICI had a pCR rate of 41.7% (95%CI: 35.8% - 47.5%). In terms of safety, the pooled rate of Grade≥3 irAEs was 11.7% (95% CI: 6.5%-16.9%). In subgroup analysis, the Grade≥3 irAEs rate of ICI monotherapy, dual-ICIs therapy, and GC plus ICI therapy was 7.4% (95% CI: 4.3%-10.5%), 30.3% (95% CI: 15.3%-45.3%), and 14.5% (95% CI: 3.5% - 25.4%), respectively. Besides, the pooled Grade≥3 TRAEs rate for chemoimmunotherapy was 32.4% (95% CI: 13.1% - 51.6%).ConclusionNeoadjuvant immunotherapy and chemoimmunotherapy were effective and safe in the treatment of MIBC. Compared to ICI monotherapy, dual-ICIs therapy or chemoimmunotherapy can improve the response rate, while increasing the morbidity of Grade≥ 3 irAEs or Grade≥ 3 TRAEs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD4202233771.

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1059P NEMIO: A randomized phase I-II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma

Abstract: A randomized phase I-II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/-tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma

Cited by 3 publications

References 0 publications

Role of immunotherapy in localized muscle invasive urothelial cancer

Role of immunotherapy in localized muscle invasive urothelial cancer

Neoadjuvant Immunochemotherapy in the Treatment of Nonmetastatic Muscle-Invasive Bladder Cancer: A Systematic Review

Neoadjuvant immunotherapy and chemoimmunotherapy for stage II-III muscle invasive bladder cancer

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