As reported in JAMA Network Open by Mamtani et al, a retrospective cohort study of patients with metastatic urothelial cancer showed population-level increases in survival after the introduction of novel cancer therapeutics—immune checkpoint inhibitors (ie, pembrolizumab and atezolizumab) and antibody-drug conjugates (ie, enfortumab vedotin-ejfv).
“Only one prior study examined temporal trends in survival among patients with metastatic urothelial cancer, but the analysis limited cohort entry to 2020 and was therefore unable to assess survival changes after antibody-drug conjugate adoption in 2020,” the investigators commented. “Our data allow clinicians and researchers to characterize the contemporary survival benefits of immune checkpoint inhibitors and antibody-drug conjugates for patients in routine care and may be used to benchmark outcomes from future clinical trials.”
Study Details
Using the U.S. nationwide electronic health record–derived Flatiron Health database, the investigators identified patients with metastatic urothelial cancer who initiated first-line systemic therapy between January 1, 2011, and September 30, 2023, with follow-up through September 30, 2024. Those who were untreated or receiving clinical trial drugs were excluded.
The study sample (n = 8,955; median age = 72.1 years) was divided into three time periods based on when first-line therapy was initiated: before immune checkpoint inhibitor approval (2011–2016; n = 2,576 [28.8%]); after immune checkpoint inhibitor approval but before antibody-drug conjugate approval (2017–2019; n = 2,943 [32.9%]); and after antibody-drug conjugate approval (2020–2023; n = 3,436 [38.4%]).
Inverse probability of treatment weighting–adjusted Kaplan-Meier curves were used to compare temporal trends in median and 3-year overall survival across the cohorts. The analysis was adjusted for patient, tumor, and practice factors.
Survival Trends
The adjusted 3-year survival probability increased from 19.2% (95% confidence interval [CI] = 17.5%–20.9%) before the approval of immune checkpoint inhibitors to 23.3% (95% CI = 21.5%–24.8%) after they became available but before the introduction of antibody-drug conjugates, and then further rose to 27.6% (95% CI = 25.7%–29.4%) after antibody-drug conjugates were approved (P < .001). The investigators reported that, similarly, the median survival of treatment initiators increased from 11.1 months (2011–2016 group; 95% CI = 10.7–11.9 months) before immune checkpoint inhibitor approval to 13.6 months (2020–2023 group; 95% CI = 12.7–14.7 months) after immune checkpoint inhibitor and antibody-drug conjugate approval (P < .001).
The investigators concluded, “In this study, we found population-level increases in survival after the introduction of novel cancer therapeutics (ie, immune checkpoint inhibitors and antibody-drug conjugates). This difference reflects a clinically meaningful 8.4 percentage point absolute improvement and 44% relative improvement in long-term survival (3-year overall survival: 19.2%–27.6%) for patients initiating therapy in contemporary practice. Because approximately 38.1% of patients initiated an immune checkpoint inhibitor or antibody-drug conjugate by September 30, 2024, our results suggest that implementation of newer therapies was likely associated with the clinical benefit observed.”
Ronac Mamtani, MD, MSCE, of the University of Pennsylvania, Philadelphia, is the corresponding author of the JAMA Network Open article.
Disclosure: The study was funded by grants from the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit jamanetwork.com.
