An analysis, based on data from the JAVELIN 100 Bladder trial, found the NCCN/FACT Bladder Symptom Index-18 for assessing quality-of-life in patients with advanced urothelial carcinoma to be reliable and valid.
Through the evaluation of data from the JAVELIN 100 Bladder trial (NCT02603432), the NCCN/FACT Bladder Symptom Index-18 (NFBlSI-18) demonstrated evidence of reliability, validity, and responsiveness to evaluate quality-of-life (QOL) in patients with locally advanced or metastatic urothelial carcinoma.1
“Community oncologists can use this brief questionnaire to benchmark their patients against those who entered the JAVELIN 100 trial and compare changes in their patients to the changes observed in the trial. The results also help evaluate the risk/benefit calculation from the trial results overall,” David Cella, PhD, professor and founding chair, department of medical social sciences at Feinberg School of Medicine, Northwestern University, told Targeted OncologyTM. “The most immediate practical value is that this allows for proper planning of future bladder cancer clinical trials and registries that opt to use this patient-reported outcome measure.”
According to findings from an analysis published in the American Cancer Society, correlations with EuroQoL-5D utility index (EQ-5D-5L UI) and visual analog scale (VAS) ranged from 0.53 to 0.73, and standardized effect sizes were >0.20. Compared with patients with time to tumor progression (TTP) of ≥6 months, patients with TTP of >0-2 and 3-5 months had larger declines. For best overall response (BOR), results were similar between patients.
For the meaningful between-group differences threshold, the NFBISI-18 total was 6-11 points, disease-related symptoms-physical was 3-6 points, DRS-emotional (DRS-E) was 1 point and function/well-being (F/WB) was 1 point as well. Thresholds for meaningful within-group worsening included 4 points total for NFBISI-18 along with 3 for DRS-P. For significant individual change these points were 3-9 for NFBISI-18, 2-6 for DRS-P, 1-3 for DRS-E, 1-3, and 2-4 for F/WB.
“Using data from the JAVELIN 100 Bladder cancer trial, we provided practical information regarding the reliability and validity of a targeted symptom index for people with advanced bladder cancer. Specifically, we provide reproducible estimates of meaningful change in the components of this questionnaire that address disease-related symptoms and functional well-being,” Cella said.
JAVELIN Bladder 100 was a randomized phase 3 trial which compared avelumab plus best supportive care (BSC) vs BSC alone in patients with locally advanced or metastatic urothelial carcinoma without disease progression with first-line platinum-containing chemotherapy.2
“The NFBlSI-18 is a reliable, valid, and responsive patient-reported outcome tool that can be used as an outcome in clinical trials to capture changes in symptoms of bladder cancer. This tool is fit for purpose in determining patient-centric benefit and risk of bladder cancer treatments,” Devin Peipert, PhD, Northwestern University Feinberg School of Medicine, told Targeted Oncology.
This trial looked at NFBlSI-18 and 5-level EQ-5D-5L longitudinally at day 1 of each cycle through maintenance treatment, at the end of treatment (EOT), and 30, 60, and 90 days after EOT. Treatment was ended if patients had confirmed disease progression, if the patient refused treatment, if there was loss to follow-up, if unacceptable toxicity was observed, as determined by the participating oncologist and patient, or if there was sponsor-initiated termination for other reasons. The time from baseline to EOT varied between patients.
This analysis utilized pooled data across both treatment arms from the initial analysis of the JAVELIN Bladder 100 trial at the data cutoff date of October 21, 2019. At this time, the maximum follow-up was 40 cycles over about 40 months.
A total of 685 patients of the 700 randomized individuals in JAVELIN Bladder 100 were eligible for inclusion in this analysis as they had baseline PRO time points occurring before their first study drug dose. Of the 685 patients, 663 (97%) PRO-eligible patients had any NFBlSI-18 data at baseline. At EOT, 448 of 560 (80%) PRO-eligible patients had any NFBlSI-18 data.
Findings showed that among patients with >0-2 or 3-6 months to tumor progression, there were significantly lower slopes for change in NFBlSI-18 Total and DRS-P scores compared with patients with ≥6 months to tumor progression. Patients with progressive disease (PD) and stable disease (SD) also had significantly lower slopes on the NFBlSI-18 Total and DRS-P scales vs patients with complete responses (CR) or partial response (PR). Further, patients with PD had significantly lower slopes on the F/WB scale compared with patients who had a CR or PR.
Changes in NFBlSI-18 scale scores from baseline to EOT in patients with >0-2 or 3-5 months to tumor progression were statistically significant, showing medium magnitude changes (absolute values of 0.50 < SRM < 0.80) in the expected direction, except for the DRS-E and F/WB scales (0.20 < SRM < 0.50).
Generally, patients with ≥6 months to tumor progression had nonsignificant changes below the threshold for small magnitude (0.2 standard deviation units), except for the DRS-P scale (SRM = −0.27; P =.01). Among patients with SC and PD based on the BOR anchor, statistically significant changes of medium magnitude (0.50 < SRM < 0.80) from baseline to EOT were seen, except for the DRS-E and patients with SD on the F/WB.
Specifically, patients reporting worsening side effects (GP5 item) or decreased QOL (EQ-5D-5L UI and VAS) had significant changes vs those who did not report worsening.
Based on these data, change thresholds have been established for future studies. Additionally, this analysis shows the reliability and validity of the NFBISI-18 to measure disease-related symptoms and health-related QOL in patients with locally advanced or metastatic urothelial cancer.
“Community oncologists, especially those participating in trials, should be aware of NFBlSI-18 tool to systematically and reliably capture symptoms that affect patients’ quality of life, which in turn can drive better symptom management,” added Peipert. “Next steps for this research will be embedding the NFBlSI-18 tool as an important outcome in future bladder cancer trials.”