China
Africa
Explore chapters and articles related to this topic
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In 2019, enfortumab vedotin-ejfv was approved by the FDA for the treatment of adult patients with locally advanced or metastatic urothelial cancer who had previously received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy. It was approved based on the results of a clinical trial that enrolled 125 patients with locally advanced or metastatic urothelial cancer who had received prior treatment with a PD-1/PD-L1 inhibitor and platinum-based chemotherapy. The overall response rate, based on the percentage of patients experiencing tumor shrinkage, was 44%, with 12% and 32% having complete and partial responses, respectively.
Bladder Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
The role of second-line chemotherapy is debated. Patients who respond to first-line therapy and remain of good performance status may achieve reasonable response rates when retreated with the same chemotherapy or an alternative first-line therapy. For instance, in a French report, accelerated MVAC after first-line gemcitabine/platinum achieved response rates of over 50% though at the cost of significant toxicity including treatment deaths.111 (A number of other combinations such as gemcitabine/paclitaxel and paclitaxel/carboplatin have112 been tested in phase II studies and have achieved response rates of around 20–30% and median progression-free survival of around 4–6 months.) The only randomized trial in second-line therapy tested the third-generation vinca alkaloid, vinflunine, against best supportive care. Median survival was non-significantly improved from 4.6 months on best supportive care to 6.9 months with vinflunine (HR 0.88 CI 0.69–1.12; p = 0.29).113 This result was significant in the eligible patient population and on this basis is the first treatment licensed for use as second-line treatment. Recent interest has centered on emerging data on antibody conjugated therapy such as enfortumab vedotin which is targeted against nectin-4 that is expressed on most bladder cancers. A phase II trial reported a 44% ORR as third-line therapy.114
Clinical development of antibody-drug conjugates in triple negative breast cancer: can we jump higher?
Published in Expert Opinion on Investigational Drugs, 2022
In one of the first preclinical characterizations of enfortumab, in vitro and in vivo antitumor activity was demonstrated against hormone receptor positive, as well as TNBC disease, with complete eradication of established tumors [62]. On the basis of these data, EV-202, a phase II monotherapy study assessing enfortumab vedotin in patients with select previously treated metastatic solid tumors is being conducted; among the 6 tumor types and respective cohorts of the study, one is dedicated to patients with metastatic TNBC [65]. Of note, Nectin 4 expression is not an inclusion criterion for entry in the study, however this marker will be assessed retrospectively. This study will indicate whether the preclinical activity reported in the TNBC setting can translate into clinical benefit for these patients.
Enfortumab Vedotin, a fully human monoclonal antibody against Nectin 4 conjugated to monomethyl auristatin E for metastatic urothelial Carcinoma
Published in Expert Opinion on Investigational Drugs, 2019
Bradley A McGregor, Guru Sonpavde
Following platinum therapy and PD1/PDL1 checkpoint inhibition, systemic therapeutic options for metastatic urothelial carcinoma are limited for a majority of patients. Erdafitinib is an excellent option for post-platinum patients (with or without PD1/PDL1 inhibitor exposure) with an activating mutation in FGFR3/2 though unfortunately this remains a minority of patients. Enfortumab vedotin is a well-tolerated drug with impressive efficacy in unselected patients with heavily treated urothelial carcinoma. The response rate of 44% with CR rate of 9% and median OS of nearly 1 year [24] is unprecedented and rivals responses seen with cisplatin-based combination chemotherapy in the front line setting [2,4]. The activity in patients with liver metastases is particularly noteworthy given the generally poor prognosis in these patients.
An evaluation of the efficacy and safety of erdafitinib for the treatment of bladder cancer
Published in Expert Opinion on Pharmacotherapy, 2020
Jones T. Nauseef, Dario M. Villamar, Justin Lebenthal, Panagiotis J. Vlachostergios, Scott T. Tagawa
It is a welcomed problem for clinicians and patients to have more than one drug for a particular target or pathway. With respect to the FGFR pathway, additional pan-FGFR inhibitors including rogaratinib, and infigratinib plus the monoclonal antibody vofatamab are in clinical development, with some differences in study design or/and development. Via a separate mechanism of action, enfortumab vedotin is available for the patients with mUC and prior progression ICI and chemotherapy (agnostic to qualifying FGFR genomic alterations). Besides testing additional drugs, moving these drugs into earlier stages of disease are underway. Of note, one major unmet need is for those patients with BCG-resistant non-muscle invasive UC, a tumor type enriched with FGFR3 alterations.