Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial

Sharma, Padmanee; Retz, Margitta; Siefker-Radtke, Arlene; Baron, Ari David; Necchi, Andrea; Bedke, Jens; Plimack, Elizabeth R.; Vaena, Daniel A.; Grimm, Marc‐Oliver; Bracarda, Sergio; Arranz, José Ángel; Pal, Sumanta K.; Οhyama, Chikara; Saci, Abdel; Qu, Xiaotao; Lambert, Alexandre; Krishnan, Suba; Azrilevich, Alex; Galsky, Matthew D.

doi:10.1016/s1470-2045(17)30065-7

Cited by 1,471 publications

(1,245 citation statements)

References 29 publications

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“…Meanwhile, other products of nanotechnology such as paclitaxel and docetaxel loaded into hydrophobically derivatized hyperbranched polyglycerols or mucoadhesive polymers for delivering the drugs in a more efficient way to endothelium is currently being under investigation. [67,68] Checkpoint inhibitors are one of the breakthroughs in BC and currently atezolizumab and nivolumab, monoclonal antibodies targeting PD-L1 on both the tumor and T cells have become almost the standard of care for patients with advanced and metastatic BC which progressed after platinum-based therapy. [69,70] Currently some studies are recruiting patients using different regimens such as atezolizumab (NCT02792192, NCT02844816) and pembrolizumab (NCT02625961) and their outcomes are awaited.…”

Section: Future Conceptsmentioning

confidence: 99%

Alternative therapies in patients with non-muscle invasive bladder cancer

Şanlı

Lotan

2017

Turkish Journal of Urology

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Bladder cancer (BC) is one of the leading causes of cancer-related deaths worldwide. Despite, the majority of the cases were diagnosed as non-muscle invasive bladder cancer (NMIBC) with favorable prognosis, it has tendency to recur or progress to a higher grade or stage. The first line treatment of patients with NMIBC is transurethral resection with adjuvant therapies primarily intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. However, in a portion of patients whose BCG treatment failed, alternative treatments may be required. Furthermore, intravesical BCG may be contraindicated in or untolerated by a group of patients. For these patients, some treatment options are readily available and a variety of them are currently under clinical investigation. In this review, these alternative therapies have been summarized.

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Section: Future Conceptsmentioning

confidence: 99%

Alternative therapies in patients with non-muscle invasive bladder cancer

Şanlı

Lotan

2017

Turkish Journal of Urology

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“…The immunologic profile of the tumor can be taken into consideration when selecting appropriate patients. The level of PD-L1 expression within tumor cells and/or immune cells is associated with higher ORR or longer OS following treatment wi th PD-1/PD-L1 blockers in N SCLC and UC, pembrolizumab in HNSCC, and nivolumab in melanoma [23,24,27,32,41,42,44,49,54,60,62]. However, some patients with low or no levels of PD-L1 expression also respond to ICBs [27], indicating that PD-L1 expression is enriched for responders, but the absence of expression is not an absolute indicator of lack of benefit.…”

Section: Immunotherapeutics and Patient Selectionmentioning

confidence: 99%

“…In fact, tumor mutational burden, known to enhance neoantigen formation, has been shown to be associated with increased response to ICBs, and in some cases improved OS as well, across tumor types such as melanoma [99,100], NSCLC [101], and UC [54,56,102]. Baseline gene expression profiling has also been correlated with response to ICBs; specifically, interferon gamma (IFNγ) signature, which is indicative of an inflammatory tumor microenvironment, is associated with responsiveness to ICBs in several tumor types, including melanoma [103], UC [32,54,104,105], NSCLC [58,106], HNSCC [103], and gastric cancer [103].…”

Section: Immunotherapeutics and Patient Selectionmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

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“…One key discovery was that immune selfregulation through immune checkpoints, a process that limits autoimmunity, may be usurped during tumorigenesis. This led to the development of immune checkpoint inhibitors, which received US FDA approval in a variety of advanced solid tumors including metastatic melanoma, non-small-cell lung cancer, squamous carcinoma of the head neck and urothelial carcinoma [1][2][3][4][5][6][7][8][9][10]. Although immune checkpoint inhibitors have allowed large numbers of patients with otherwise incurable malignancies to achieve long-term remissions, often with limited side effects, response rates tend to be modest.…”

Section: Immunotherapy In Cancermentioning

confidence: 99%

Melanoma Treatment with Intratumoral Electroporation of Tavokinogene Telseplasmid (pIL-12, Tavokinogene Telseplasmid)

Canton¹,

Shirley²,

Wright³

et al. 2017

Immunotherapy

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Tumors evade detection and/or clearance by the immune system via multiple mechanisms. IL-12 is a potent immunomodulatory cytokine that plays a central role in immune priming. However, systemic delivery of IL-12 can result in life-threatening toxicity and therefore has shown limited efficacy at doses that can be safely administered. We developed an electroporation technique to produce highly localized IL-12 expression within tumors leading to regression of both treated and untreated lesions in animal models and in patients with a favorable safety profile. Furthermore, intratumoral tavokinogene telseplasmid electroporation can drive cellular immune responses, converting ‘cold’ tumors into ‘hot’ tumors. Clinical trials are ongoing to determine whether intratumoral tavokinogene telseplasmid electroporation synergizes with checkpoint blockade therapy in immunologically cold tumors predicted not to respond to PD-1 antibody monotherapy.

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Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial

Cited by 1,471 publications

References 29 publications

Alternative therapies in patients with non-muscle invasive bladder cancer

Alternative therapies in patients with non-muscle invasive bladder cancer

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Melanoma Treatment with Intratumoral Electroporation of Tavokinogene Telseplasmid (pIL-12, Tavokinogene Telseplasmid)

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