Antibody-drug conjugates reduce the risk of death in common bladder cancer patients by 30%

Antibody-drug conjugate (ADC) enfortumabubedothin (PADCEV)^®) Has been shown to increase survival in patients with urothelium carcinoma In a recent study. The results of a randomized, open-label, phase 3 study New England Journal of Medicine..

Urothelial cancer develops in urothelial cells and ~ 90% Of all bladder cancer.This cell type supports some components of the meaning of the urethra, in addition to the bladder, and the tumor But development Part of the ureter, urethra and kidneys.

The clinical trial enrolled 608 adult participants from 19 countries.Effectiveness of Enfortsumab Bedochin Locally advanced or metastatic urothelial cancer that has been previously treated with platinum-based chemotherapy and has progressed during or after treatment with a particular type of immunotherapy known as immunomodulatory drug (PD-1) The survey was conducted on participants whose diagnosis was confirmed. / L1 inhibitor).

The mAb component of enfortumabbedotin is Surface-binding protein Nectin-4, It is present in most bladder cancer cells. mAb is linked to a chemotherapeutic agent called Monomethyloristatin E (MMAE). MMAE can prevent the polymerization of tubulin, which is required for the formation of microtubules. Microtubules are an important element that enables cell division. When taken up by cancer cells, MMAE interferes with the formation of microtubes, prevents cell proliferation and induces apoptosis.

“This new type of drug has provided survival benefits for bladder cancer that were difficult to achieve with this difficult disease. This is really because it reduced mortality by 30% and beat chemotherapy in all situations. It’s a big problem. ”

– –

Tom Pauls, Professor of Urogenital Oncology, Queen Mary University of London, and Director of the Barts Cancer Center at Barts Health NHS Trust.

Study design and important discoveries

Study participants receive enfortumabbedotin (n = 301) at a dose of 1.25 mg / kg body weight on days 1, 8 and 15 of the 28-day treatment cycle, or chemotherapy (n = 307). ) Was randomly assigned to administer. One of the 21-day treatment cycles.

Effectiveness

Participants who received enfortumabbedotin had a 30% lower risk of death compared to chemotherapy. Median survival for participants receiving enfortumabbedotin was approximately 13 months, compared to approximately 9 months for chemotherapy. arm..

Median Progression-free survivalWas 5.6 months (95% CI, 5.32 to 5.82) with enfortumabbedotin, compared to 3.7 months (95% CI, 3.52 to 3.94) with chemotherapy alone.

Enfortumabbedotin has been shown to be beneficial across multiple subgroups, but there was no advantage over chemotherapy in the female patient subgroup.

Overall response rate, Defined as the percentage of full exam participants Or Partial response to treatment was 40.6% [95% CI, 34.9 to 46.5] Enfortsumab Bedotin vs. 17.9% [95% CI, 13.7 to 22.8] For chemotherapy onlyP <0.001.

safety

“The overall incidence of treatment-related adverse events was high, but similar in the two groups,” the authors of the study said. Treatment-related side effects are defined as having a reasonable possibility that they were caused by treatment.Most adverse events observed in the trial were mild to moderate, but the authors emphasized that some patients may experience them. Serious adverse events At the time of administration of enfortumabbedotin. Therefore, it should be carefully monitored for signs of a rash (which is likely to be associated with the presence of Nectin-4 in the skin), peripheral neuropathy, and hyperglycemia. The incidence of treatment-related deaths in the enfortumabbedotin group was similar to previous studies in patients with this type of cancer.

In summary, patients with urothelial cancer who received enfortumabbedotin were observed to have significantly longer overall survival and progression-free survival, achieving higher overall survival compared to the chemotherapy group. It was.

reference: Powles T, Rosenberg JE, Sonpavde GP, etc. Enfortumabbedotin in previously treated advanced urothelial cancer. New engineering J. Med. 2021. doi:10.1056 / NEJMoa2035807