Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial

Powles, Thomas; Durán, Ignacio; Heijden, Michiel S. van der; Loriot, Yohann; Vogelzang, Nicholas J.; Giorgi, Ugo De; Oudard, Stéphane; Retz, Margitta; Castellano, Daniel; Bamias, Aristotelis; Fléchon, Aude; Gravis, Gwénaëlle; Hussain, Syed A.; Takano, Toshimi; Leng, Ning; Kadel, Edward E.; Banchereau, Romain; Hegde, Priti S.; Mariathasan, Sanjeev; Cui, Na; Shen, Xiaodong; Derleth, Christina Louise; Green, Marjorie C.; Ravaud, Alain

doi:10.1016/s0140-6736(17)33297-x

Cited by 1,208 publications

(1,110 citation statements)

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“…The frequency of positive PD‐L1 assay outcome was lower than described in previous trials using the PD‐L1 (SP142) assay in advanced and metastatic bladder cancer, which reported a positive assay outcome in 25–32% . A possible explanation for this discrepancy might be the composition of study cohorts.…”

Section: Discussioncontrasting

confidence: 58%

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Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens

et al. 2018

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Section: Discussioncontrasting

confidence: 58%

“…PD‐L1 expression was scored according to the manufacturer's guidelines . Briefly, PD‐L1 staining on immune cells was assessed in urothelial carcinoma areas occupied by tumour cells, associated intratumoral and contiguous peritumoral stroma.…”

Section: Methodsmentioning

confidence: 99%

Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens

et al. 2018

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“…Although this study was limited by phase II trial, atezolizumab received US-FDA approval for platinum-refractory mUC in May 2016 [202122]. In a recent multi-center, randomized phase III IMvigor211 clinical trial (NCT02302807), the clinical efficacy and safety of atezolizumab (1,200 mg intravenously, every three weeks) compared to chemotherapy (investigator's choice of vinflunine, paclitaxel, or docetaxel) were reported in 931 patients with mUC, whose disease had progressed despite platinum-based chemotherapy [23]. As a primary endpoint of the trial with atezolizumab, no significant improvement of OS was observed in the subset of 234 patients with ≥5% expression of PD-L1 on tumor-infiltrating ICs (median, 11.1 months vs. 10.6 months; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.63–1.21); ORR was similar (23% vs. 22%).…”

Section: Immune Checkpoint Inhibitors After Platinum-based Chemotheramentioning

confidence: 99%

Immune checkpoint inhibitors for urothelial carcinoma

Kim

Seo

2018

Investig Clin Urol

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Urothelial carcinoma (UC), originating in the bladder or upper urinary tract, is the most common histological type of cancer. Currently, platinum-based cytotoxic chemotherapy is the standard treatment for metastatic UC (mUC) and the preferred treatment option in the perioperative (neoadjuvant and/or adjuvant) setting of muscle invasive bladder cancer (MIBC). In addition, intravesical bacillus Calmette-Guerin immunotherapy or chemotherapy is applied as the adjuvant therapeutic option in non-muscle invasive bladder cancer (NMIBC) after transurethral resection, to prevent recurrence and progression. In recent years, with an increased understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibition has been explored and clinically used in the area of UC. The programmed cell death 1 receptor (PD-1) and its ligand (PD-L1) are important negative regulators of immune activity, preventing the destruction of normal tissues and autoimmunity. To date, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US-FDA) for first- or second-line use in mUC, based on durable therapeutic response and manageable safety profiles observed in relevant clinical trials. In addition, the clinical use of several immune checkpoint inhibitors is currently being tested for MIBC and NMIBC. In this article, we review the current and ongoing clinical trials, regarding immune checkpoint inhibitors, being conducted in various clinical settings of UC, including mUC, MIBC, and NMIBC.

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“…Based on these results, atezolizumab received accelerated approval as a first‐line treatment for cisplatin‐ineligible patients with locally advanced or mUC. However, the result of a randomized, open‐label, phase III trial (IMvigor211; n = 931) showed that atezolizumab use in platinum‐refractory mUC patients ( n = 234 [25%]) with ≥5% expression of PD‐LI on tumor infiltrating immune cells did not show statistically significant benefits in OS as compared with the OS benefits after chemotherapy . Grade ≥3 adverse events occurred in 20% with atezolizumab and in 43% with chemotherapy.…”

Section: Immunotherapy In Ucmentioning

confidence: 99%

Immunotherapy for genitourinary tumors

Nakayama

Kitano

2019

Int J of Urology

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The present review provides an update about the major achievements and recent advances of immunotherapy in renal cell carcinoma, urothelial carcinoma, and prostate cancer. Although the treatment strategy for renal cell carcinoma and urothelial carcinoma includes traditional cancer immunotherapies, such as interleukin‐2 and interferon‐alfa, the clinical outcomes of these therapies are unsatisfactory. In recent years, the development of immune checkpoint inhibitors has drastically changed the treatment strategy for various cancers, including genitourinary cancer. The present review summarizes the approved cancer immunotherapies for renal cell carcinoma, urothelial carcinoma and prostate cancer. Furthermore, we review the response evaluation and biomarkers for immune checkpoint inhibitors with a distinctive mode of action that is different from cytotoxic agents. Finally, future perspectives for cancer immunotherapy are discussed.

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Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial

Abstract: F Hoffmann-La Roche, Genentech.

Cited by 1,208 publications

References 30 publications

Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens

Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens

Immune checkpoint inhibitors for urothelial carcinoma

Immunotherapy for genitourinary tumors

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