Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 384(12), P. 1125 - 1135

Published: Feb. 12, 2021

Patients with advanced urothelial carcinoma have poor overall survival after platinum-containing chemotherapy and programmed cell death protein 1 (PD-1) or ligand (PD-L1) inhibitor treatment.We conducted a global, open-label, phase 3 trial of enfortumab vedotin for the treatment patients locally metastatic who had previously received disease progression during PD-1 PD-L1 inhibitor. were randomly assigned in 1:1 ratio to receive (at dose 1.25 mg per kilogram body weight on days 1, 8, 15 28-day cycle) investigator-chosen (standard docetaxel, paclitaxel, vinflunine), administered day 21-day cycle. The primary end point was survival.A total 608 underwent randomization; 301 307 chemotherapy. As July 15, 2020, deaths occurred (134 group 167 group). At prespecified interim analysis, median follow-up 11.1 months. Overall longer than (median survival, 12.88 vs. 8.97 months; hazard death, 0.70; 95% confidence interval [CI], 0.56 0.89; P = 0.001). Progression-free also progression-free 5.55 3.71 0.62; CI, 0.51 0.75; P<0.001). incidence treatment-related adverse events similar two groups (93.9% 91.8% group); grade higher (51.4% 49.8%, respectively).Enfortumab significantly prolonged as compared standard platinum-based (Funded by Astellas Pharma US Seagen; EV-301 ClinicalTrials.gov number, NCT03474107.).

Language: Английский

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The Next Decade of Immune Checkpoint Therapy

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 838 - 857

Published: April 1, 2021

Immune checkpoint therapy (ICT) can provide durable clinical responses and improve overall survival. However, only subsets of patients with specific tumor types respond to ICT. Thus, significant challenges remain, including understanding pathways resistance, optimizing patient selection, improving management immune-related adverse events, identifying rational therapeutic combinations. These will need a focused approach encompassing both basic research, the integration reverse translational studies. This integrated lead identification potential targets for subsequent trials, which guide decisions as we develop novel combination strategies maximize efficacy minimize toxicities patients. SIGNIFICANCE: ICTs induce antitumor cancer. Recent evidence suggests that combinatorial response by overcoming primary adaptive resistance mechanisms, although these may carry an increased risk immune-mediated toxicities. review surveys current mechanisms active areas investigation, proposes path forward minimizing through better selection

Language: Английский

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DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 9, 2021

Abstract Genomic instability is the hallmark of various cancers with increasing accumulation DNA damage. The application radiotherapy and chemotherapy in cancer treatment typically based on this property cancers. However, adverse effects including normal tissues injury are also accompanied by chemotherapy. Targeted therapy has potential to suppress cells’ damage response through tailoring patients lacking specific functions. Obviously, understanding broader role repair became a basic attractive strategy for targeted therapy, particular, raising novel hypothesis or theory field basis previous scientists’ findings would be important future promising druggable emerging targets. In review, we first illustrate timeline steps roles promotion developed, then summarize mechanisms regarding associated highlighting proteins behind targeting that initiate functioning abnormally duo extrinsic harm environmental factors, also, baseline drift leads harmful intrinsic therapy. addition, clinical therapeutic drugs effects, as well scheme relative trials were intensive discussed. Based background, suggest two hypotheses, namely “environmental gear selection” describe pathway evolution, “DNA drift”, which may play magnified mediating during treatment. This new shed light provide much better more comprehensive holistic view promote development research direction overcoming strategies patients.

Language: Английский

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Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial

The Lancet Oncology, Journal Year: 2021, Volume and Issue: 22(7), P. 931 - 945

Published: May 26, 2021

Language: Английский

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Combination strategies to maximize the benefits of cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Sept. 27, 2021

Abstract Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary secondary resistance to single agent immunotherapy often results treatment failure, only a minority of experience long-term benefits. This review article will discuss the relationship between response mechanisms immunotherapy. It also provide comprehensive on latest clinical status combination therapies (e.g., with chemotherapy, radiation targeted therapy), approved by US Food Drug Administration. an overview targeting cytokines other soluble immunoregulatory factors, ACT, virotherapy, innate modifiers vaccines, well that exploit alternative targets therapeutic modalities. Finally, this include stimulating insights from 2020 China Immuno-Oncology Workshop co-organized Chinese American Hematologist Oncologist Network (CAHON), National Medical Product Administration (NMPA) Tsinghua University School Medicine.

Language: Английский

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Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Annals of Oncology, Journal Year: 2021, Volume and Issue: 33(3), P. 244 - 258

Published: Nov. 30, 2021

Language: Английский

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Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 390(10), P. 875 - 888

Published: March 6, 2024

No treatment has surpassed platinum-based chemotherapy in improving overall survival patients with previously untreated locally advanced or metastatic urothelial carcinoma. Download a PDF of the Research Summary. We conducted phase 3, global, open-label, randomized trial to compare efficacy and safety enfortumab vedotin pembrolizumab Patients were randomly assigned 1:1 ratio receive 3-week cycles (at dose 1.25 mg per kilogram body weight intravenously on days 1 8) 200 day 1) (enfortumab vedotin–pembrolizumab group) gemcitabine either cisplatin carboplatin (determined basis eligibility cisplatin) (chemotherapy group). The primary end points progression-free as assessed by blinded independent central review survival. A total 886 underwent randomization: 442 group 444 group. As August 8, 2023, median duration follow-up for was 17.2 months. Progression-free longer than (median, 12.5 months vs. 6.3 months; hazard disease progression death, 0.45; 95% confidence interval [CI], 0.38 0.54; P<0.001), 31.5 16.1 0.47; CI, 0.58; P<0.001). number 12 (range, 46) 6 6) Treatment-related adverse events grade 3 higher occurred 55.9% 69.5% those Treatment resulted significantly better outcomes carcinoma, profile consistent that previous reports. (Funded Astellas Pharma US others; EV-302 ClinicalTrials.gov number, NCT04223856.) QUICK TAKE VIDEO SUMMARYEnfortumab Vedotin–Pembrolizumab Advanced Urothelial Cancer 02:22

Language: Английский

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European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update

European Urology, Journal Year: 2023, Volume and Issue: 84(1), P. 49 - 64

Published: March 24, 2023

Language: Английский

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Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: April 7, 2022

Abstract The main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor system by myriad mechanisms. After that, scientists focused on molecules mainly. Thereby, much effort spent to progress novel strategies for suppressing these inhibitory axes, resulting evolution inhibitors (ICIs). Then, ICIs have become promising approach and shaped paradigm shift immunotherapies. CTLA-4 plays an influential role attenuation induction naïve memory T cells engagement with its responding ligands like B7-1 (CD80) B7-2 (CD86). Besides, PD-1 is predominantly implicated adjusting cell function peripheral tissues through interaction programmed death-ligand 1 (PD-L1) PD-L2. Given their suppressive effects anti-tumor immunity, it has firmly been documented that based therapies can be practical rational therapeutic approaches treat cancer patients. Nonetheless, inherent or acquired resistance ICI some treatment-related toxicities restrict application clinic. current review will deliver comprehensive overview human tumors alone combination other modalities support more desired outcomes lower

Language: Английский

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The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma

European Urology, Journal Year: 2021, Volume and Issue: 81(1), P. 95 - 103

Published: Nov. 3, 2021

Language: Английский

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