Key Points :
Padcev plus Keytruda enhanced event-free and overall survival of cisplatin-ineligible MIBC patients over surgery.
The combination therapy also doubled the complete disappearance of the cancer rate, the first anywhere in these patients.
Key Background :
Muscle-invasive bladder cancer (MIBC) is a aggressive type of the disease where the cancer grows into the muscle layer of the bladder. It is etiologically responsible for approximately one-quarter to one-third of bladder cancers at diagnosis. The optimal treatment in appropriate patients is neoadjuvant cisplatin-based chemotherapy and radical cystectomy and has been demonstrated to enhance survival. The majority of patients, however, are not candidates for cisplatin due to underlying renal insufficiency, advanced age, or other illness. Surgery has been the mainstay in these patients, addressing a wonderful therapeutic demand.
Padcev or enfortumab vedotin is an antibody-drug conjugate that targets the Nectin-4 protein that is found on bladder cancer cells to a significant extent. It targets the very potent chemotherapy drug to the cancer cells without affecting the stability of the balance of the remaining healthy tissue. Keytruda or pembrolizumab is an immune checkpoint inhibitor that inhibits the PD-1 protein so that the immune system can identify the cancer cells and eliminate them. Clinical trials are achieving record success with the drug combination for treating advanced bladder cancer.
The EV-303 trial randomly assigned cisplatin-ineligible patients with MIBC to Padcev and Keytruda pre- and postoperatively, Keytruda alone in the same perioperative regimen, or surgery. Interim results revealed that combination therapy dramatically improved event-free survival and overall survival and increased complete eradication of the tumor following surgery at a higher rate than with surgery alone. Systemic therapy never provided this advantage to these patients, to our knowledge.
Dr. Christof Vulsteke called the findings a breakthrough in bladder cancer treatment, stating that no systemic therapy ever had yielded such good results in patients. Pfizer's Johanna Bendell stated that the discovery may change the course of treatment for early disease.
Safety results of combination therapy were expected with all drugs having well-documented side-effects, and there were no unforeseen safety issues. This indicates that the regimen can be both safe and effective in patients who otherwise have nothing else to provide in terms of systemic therapy.
Pfizer and Astellas plan to seek approval for this new indication for Padcev using Keytruda as well and already are considering the combination in cisplatin-eligible patients in the EV-304 trial. As a successfully marketed medicine, treatment can provide life-extending therapy for thousands of bladder cancer patients globally who have had few therapeutic options for decades.
About the Author
Kevin Smith
Kevin Smith is a Managing Editor at World Care Magazine.