Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma

Powles, Thomas; O’Donnell, Peter H.; Massard, Christophe; Arkenau, Hendrik Tobias; Friedlander, Terence W.; Hoimes, Christopher J.; Lee, Jae‐Lyun; Ong, Michael; Sridhar, Srikala S.; Vogelzang, Nicholas J.; Fishman, Mayer; Zhang, Jingsong; Srinivas, Sandy; Parikh, J. R.; Antal, Joyce; Jin, Xiaoping; Gupta, Ashok; Ben, Yong; Hahn, Noah M.

doi:10.1001/jamaoncol.2017.2411

Cited by 760 publications

(509 citation statements)

References 18 publications

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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%

“…Though imAE onset is variable, most occur during the initial months of therapy [11][12][13][14][15][16]. Whereas imAEs of any grade can occur in up to 90% of patients treated with ICBs as monotherapy [17,20,24,36,42,43,54,56,59,62], the incidence of grade ≥ 3 imAEs can range from 1% to 10% with anti-PD-1/PD-L1 monotherapy [24,43,54,56,59,62] and from 15% to 42% with anti-CTLA-4 monotherapy [17,20,24,36]. Combination therapy with anti-CTLA-4 and anti-PD-1 antibodies is associated with a 40% to 45% incidence of grade ≥ 3 imAEs [24,36].…”

Section: Adverse Events Associated With Icbsmentioning

confidence: 99%

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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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Section: Immunotherapeutics and Patient Selectionmentioning

confidence: 99%

Section: Adverse Events Associated With Icbsmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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“…The overall ORR was 17.8% (95% CI 12.7–24.0%), including 7% complete responses (CR). ORRs were 27.6% (95% CI 19.0–37.5%) and 5.1% (95% CI 1.4–12.5%) in patients with high and low or negative expression of PD-L1, respectively [11]. Median PFS and OS periods were 1.5 months (95% CI 1.4–1.9 months) and 18.2 months (95% CI 8.1 months to not estimable), respectively [11].…”

Section: Introductionmentioning

confidence: 99%

“…ORRs were 27.6% (95% CI 19.0–37.5%) and 5.1% (95% CI 1.4–12.5%) in patients with high and low or negative expression of PD-L1, respectively [11]. Median PFS and OS periods were 1.5 months (95% CI 1.4–1.9 months) and 18.2 months (95% CI 8.1 months to not estimable), respectively [11]. Severe AEs (grade 3–4) and grade 3–4 immune-mediated AEs occurred in 6.8 and 2.1% of the patients, respectively [11].…”

Section: Introductionmentioning

confidence: 99%

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Recent advances in medical therapy for metastatic urothelial cancer

2018

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Cytotoxic chemotherapy has been the mainstay of medical therapy for metastatic urothelial cancer. Currently, the gemcitabine/cisplatin regimen is widely used worldwide as the standard first-line medical treatment. Very recently, in 2017, pembrolizumab, a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1, was approved as a second-line treatment to be used after platina-based chemotherapy for metastatic urothelial cancer in Japan. Based on its promising anti-tumor efficacy and manageable safety profile as demonstrated in the phase III KEYNOTE-045 trial, pembrolizumab therapy is expected to be rapidly introduced for treating metastatic urothelial cancer in clinical practice. The paradigm of medical treatment for patients with metastatic UC is dramatically changing through the introduction of this and other immune-checkpoint inhibitors. In this article, we provide a brief overview of these immune-checkpoint inhibitors and a comprehensive summary of the use of cytotoxic chemotherapy for metastatic urothelial cancer, including ongoing clinical trials.

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Bladder Cancer

Lenis

Lec

Chamie³

et al. 2020

JAMA

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ImportanceBladder cancer is a common malignancy in women and is the fourth most common malignancy in men. Bladder cancer ranges from unaggressive and usually noninvasive tumors that recur and commit patients to long-term invasive surveillance, to aggressive and invasive tumors with high disease-specific mortality.ObservationsAdvanced age, male sex, and cigarette smoking contribute to the development of bladder cancer. Bladder tumors can present with gross or microscopic hematuria, which is evaluated with cystoscopy and upper tract imaging depending on the degree of hematuria and risk of malignancy. Non–muscle-invasive tumors are treated with endoscopic resection and adjuvant intravesical therapy, depending on the risk classification. Enhanced cystoscopy includes technology used to improve the detection of tumors and can reduce the risk of recurrence. Patients with high-risk non–muscle invasive tumors that do not respond to adjuvant therapy with the standard-of-care immunotherapy, bacille Calmette-Guérin (BCG), constitute a challenging patient population to manage and many alternative therapies are being studied. For patients with muscle-invasive disease, more aggressive therapy with radical cystectomy and urinary diversion or trimodal therapy with maximal endoscopic resection, radiosensitizing chemotherapy, and radiation is warranted to curb the risk of metastasis and disease-specific mortality. Treatment of patients with advanced disease is undergoing rapid changes as immunotherapy with checkpoint inhibitors, targeted therapies, and antibody-drug conjugates have become options for certain patients with various stages of disease.Conclusions and RelevanceImproved understanding of the molecular biology and genetics of bladder cancer has evolved the way localized and advanced disease is diagnosed and treated. While intravesical BCG has remained the mainstay of therapy for intermediate and high-risk non–muscle-invasive bladder cancer, the therapeutic options for muscle-invasive and advanced disease has expanded to include immunotherapy with checkpoint inhibition, targeted therapies, and antibody-drug conjugates.

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Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma

Abstract: clinicaltrials.gov Identifier: NCT01693562.

Cited by 760 publications

References 18 publications

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Recent advances in medical therapy for metastatic urothelial cancer

Bladder Cancer

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