Patients treated with pembrolizumab (Keytruda) as second-line therapy for advanced urothelial carcinoma following platinum-based chemotherapy maintain better health-related quality of life than their counterparts receiving chemotherapy, according to results from the phase III KEYNOTE-045 trial presented at the American Society of Clinical Oncology annual meeting in Chicago.
Chicago-Patients treated with pembrolizumab (Keytruda) as second-line therapy for advanced urothelial carcinoma (UC) following platinum-based chemotherapy maintain better health-related quality of life (HRQoL) than their counterparts receiving chemotherapy, according to results from the phase III KEYNOTE-045 trial presented at the American Society of Clinical Oncology annual meeting in Chicago.
“Health-related quality of life reflects treatment efficacy and safety, and so the quality of life benefits found for pembrolizumab in KEYNOTE-045 are consistent with the superiority it demonstrated for improving overall survival compared with chemotherapy and its more favorable toxicity profile,” said Ronald de Wit, MD, PhD, professor of internal oncology at Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
“These reasons collectively render pembrolizumab as a new standard of care for patients with previously treated advanced UC.”
KEYNOTE-045 randomized 542 patients 1:1 to treatment with the anti-PD-1 humanized monoclonal antibody pembrolizumab, 200 mg every 3 weeks, or the investigator’s choice of chemotherapy with paclitaxel (Abraxane), docetaxel (Taxotere), or vinflunine (Javlor) for up to 2 years.
In the primary endpoint analysis, pembrolizumab demonstrated a statistically significant benefit for improving overall survival compared with chemotherapy (HR 0.73, p=.0022; median 10.3 vs. 7.4 months, respectively). In addition, the pembrolizumab group had a lower rate of treatment-related adverse events than the control group (60.9% vs. 90.2%) and a lower incidence of Grade 3/4 toxicities (15.0% vs 49.4%).
Quality of life data in the trial were collected using the European Organisation for Research and Treatment of Cancer (EORTC) core 30 quality of life questionnaire (EORTC QLQ-C30), which was completed by patients at cycles 1-4 (weeks 0, 3, 6, and 9) followed by every 2 cycles for up to 1 year and at 30 days after treatment discontinuation.
Mean EORTC QLQ-C30 score at baseline was similar in the pembrolizumab and chemotherapy groups (61.1 vs. 59.1). An analysis of change in HrQoL from baseline to week 15 showed no significant change in the EORTC QLQ-C30 score in the pembrolizumab group (n=157; least squares mean change +0.75) but a significant decrease in the patients receiving chemotherapy (least squares mean change –8.30), and the difference between treatment groups was statistically significant (p<.001).
The data were also analyzed using Kaplan-Meier methodology to determine time to deterioration of HrQoL as defined by a ≥10-point change in the EORTC QLQ-C30. The results showed HrQoL was better sustained in the patients on pembrolizumab compared with their chemotherapy-treated counterparts. Median time to deterioration was 3.5 months in the pembrolizumab group and 2.2 months among chemotherapy-treated patients (HR 0.70; p=.002).
Additional analyses of HrQoL considered change from baseline to week 15 with patients categorized based on whether they had disease progression. Among patients without progression, mean EORTC QLQ-C30 score improved from baseline to week 15 in the pembrolizumab group (+5.97), whereas it declined in patients receiving chemotherapy (–4.31). The EORTC QLQ-30 scores declined in both treatment groups among patients whose disease progressed, but the deterioration was less among patients treated with pembrolizumab compared with the chemotherapy control group (–3.54 vs. –13.95).
With few exceptions, analyses of changes from baseline to week 15 for the individual functional and symptom domain scores comprising the HrQoL instrument showed that pembrolizumab treatment was associated with higher rates of score improvements and lower rates of score deterioration.
Dr. de Wit has received honoraria from and served as a consultant/adviser to Lilly, Merck, Roche/Genentech, and Sanofi. His institution has received funding from Sanofi. Several of his co-authors have a financial or other relationship with Merck and/or other pharmaceutical companies.
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