Keytruda plus gemcitabine and higher doses of radiotherapy showed promising efficacy and safety results in patients with muscle-invasive bladder cancer.
Adding Keytruda (pembrolizumab) to the chemotherapy gemcitabine and hypofractionated radiotherapy (radiotherapy given over a shorter period of time in larger doses) was a promising bladder-sparing regimen for the treatment of muscle-invasive bladder cancer.
Findings from the trial were presented at the 2021 ASCO Annual Meeting by lead author Dr. Arjun V. Balar, an associate professor of medicine at the NYU Grossman School of Medicine and genitourinary medical oncology program director at NYU Langone’s Perlmutter Cancer Center.
The trial included patients with muscle-invasive bladder cancer who declined or who were ineligible for cystectomy (surgery to remove all or part of the bladder). The median age of the patient population was 74 years. Thirty-nine patients (72%) were men, and the majority of patients (70%) had stage 2 disease that did not spread to the lymph nodes. In addition, 14 men (26%) had stage 3 disease and two men (4%) had stage 4 disease.
During the trial, patients received a single 200-mg dose of Keytruda., followed by maximal transurethral resection (a surgical procedure to remove cancerous tissue) of the bladder tumor. Patients also underwent whole-bladder radiotherapy with twice weekly gemcitabine and Keytruda every three weeks for three doses. Six patients were enrolled in a safety study, and 48 patients were enrolled in an efficacy study.
The primary goal of the trial was to assess two-year bladder-intact disease-free survival, defined as muscle-invasive recurrence, regional or distant metastases, need for cystectomy or death. Other outcomes of interest in this study included safety, 12 weeks’ complete response rate (the disappearance of all targeted lesions), metastases-free survival and overall survival (the amount of time from diagnosis or treatment that a patient with the disease is still alive).
A total of 42 patients (85%) fully completed the study. Twelve patients (25%) had dose reductions of gemcitabine. One patient (2%) discontinued radiotherapy/gemcitabine, three (6%) discontinued gemcitabine only and four (8%) discontinued Keytruda.
Twelve-week complete response was 100% in the safety group and 77% in the efficacy group. The investigators reported a one-year bladder-intact disease-free survival rate in the efficacy group of 88% at a median follow-up of 14.6 months, “which is quite encouraging,” Balar said. The rate increased slightly to 89% when the safety group was added to the analysis. Metastases-free survival was 85% at one-year follow-up for the entire patient population.
In the efficacy group, the majority of treatment-related side effects were considered mild to moderate, with fatigue, nausea, diarrhea, urinary urgency, maculopapular rash (a rash with flat and raised bumps), decreased platelets and anorexia observed in at least 20% of patients. Severe to life-threatening treatment-related side effects included diarrhea, decreased lymphocyte count (potentially indicating infection), colitis (inflamed colon), fatigue, anemia, urinary tract pain, decreased potassium levels and hyponatremia (low sodium levels in blood). Other side effects of this degree occurred in these patients such as urinary tract infection, neutropenia (low white blood cell count), febrile neutropenia (development of fever with neutropenia), protein-losing enteropathy (protein-rich materials leaking into the intestine), immune-related polyneuropathy (malfunction of peripheral nerves) and colonic perforation (hole in the colon).
Researchers suspected that several side effects were related to Keytruda such as mild to moderate fatigue, maculopapular rash, alanine aminotransferase (levels depicting early liver disease) and itching. Severe side effects suspected to be related to Keytruda included immune-related protein-losing enteropathy, immune-related polyneuropathy, neutropenia and urinary tract infection. One life-threatening case of colonic perforation was observed. In addition, nine patients (19%) were treated with systemic corticosteroids for the management of an immune-related side effect.
Balar concluded, “Trimodality bladder preservation therapy is an effective nonsurgical option for patients with muscle-invasive bladder cancer and with curative intent.”
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