TY - JOUR
T1 - Effectiveness of First-line Immune Checkpoint Blockade Versus Carboplatin-based Chemotherapy for Metastatic Urothelial Cancer
AU - Feld, Emily
AU - Harton, Joanna
AU - Meropol, Neal J.
AU - Adamson, Blythe J.S.
AU - Cohen, Aaron
AU - Parikh, Ravi B.
AU - Galsky, Matthew D.
AU - Narayan, Vivek
AU - Christodouleas, John
AU - Vaughn, David J.
AU - Hubbard, Rebecca A.
AU - Mamtani, Ronac
N1 - Publisher Copyright:
© 2019 European Association of Urology
PY - 2019/10
Y1 - 2019/10
N2 - Background: Limited data compare first-line carboplatin-based chemotherapy and immune checkpoint blockade in cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. The primary evidence guiding treatment decisions was a recent Food and Drug Administration/European Medicines Agency safety alert based on emerging data from two ongoing phase III trials, reporting shorter survival in programmed death-ligand 1 (PD-L1)-negative patients receiving immunotherapy. Final results from these trials are unknown. Objective: To compare survival in cisplatin-ineligible mUC patients receiving first-line immunotherapy versus those receiving carboplatin-based chemotherapy. Design, setting, and participants: We conducted a retrospective cohort study of 2017 mUC patients receiving first-line carboplatin-based chemotherapy (n = 1530) or immunotherapy (n = 487) from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record–derived database. Outcome measurements and statistical analysis: The primary outcomes were overall survival (OS), comparing 12- and 36-mo OS, and hazard ratios before and after 12 mo. Propensity score–based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression model estimates of comparative effectiveness. Results and limitations: IPTW-adjusted OS rates in the immunotherapy group were lower at 12 mo (39.6% [95% confidence interval {CI} 34.0–45.3%] vs 46.1% [95% CI 43.4–48.8%]) but higher at 36 mo (28.3% [95% CI 21.8–34.7%] vs 13.3% [95% CI 11.1–15.5%]) relative to the chemotherapy group. Immunotherapy treatment demonstrated inferior OS during the first 12 mo relative to carboplatin-based chemotherapy (IPTW-adjusted hazard ratio [HR] 1.37, 95% CI 1.15–1.62), but superior OS beyond 12 mo (IPTW-adjusted HR 0.50, 95% CI 0.30–0.85). Limitations include retrospective design and potential unmeasured confounding. Conclusions: In the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy. Patient summary: To determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the 1st year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the 1st year, immunotherapy was superior.
AB - Background: Limited data compare first-line carboplatin-based chemotherapy and immune checkpoint blockade in cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. The primary evidence guiding treatment decisions was a recent Food and Drug Administration/European Medicines Agency safety alert based on emerging data from two ongoing phase III trials, reporting shorter survival in programmed death-ligand 1 (PD-L1)-negative patients receiving immunotherapy. Final results from these trials are unknown. Objective: To compare survival in cisplatin-ineligible mUC patients receiving first-line immunotherapy versus those receiving carboplatin-based chemotherapy. Design, setting, and participants: We conducted a retrospective cohort study of 2017 mUC patients receiving first-line carboplatin-based chemotherapy (n = 1530) or immunotherapy (n = 487) from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record–derived database. Outcome measurements and statistical analysis: The primary outcomes were overall survival (OS), comparing 12- and 36-mo OS, and hazard ratios before and after 12 mo. Propensity score–based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression model estimates of comparative effectiveness. Results and limitations: IPTW-adjusted OS rates in the immunotherapy group were lower at 12 mo (39.6% [95% confidence interval {CI} 34.0–45.3%] vs 46.1% [95% CI 43.4–48.8%]) but higher at 36 mo (28.3% [95% CI 21.8–34.7%] vs 13.3% [95% CI 11.1–15.5%]) relative to the chemotherapy group. Immunotherapy treatment demonstrated inferior OS during the first 12 mo relative to carboplatin-based chemotherapy (IPTW-adjusted hazard ratio [HR] 1.37, 95% CI 1.15–1.62), but superior OS beyond 12 mo (IPTW-adjusted HR 0.50, 95% CI 0.30–0.85). Limitations include retrospective design and potential unmeasured confounding. Conclusions: In the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy. Patient summary: To determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the 1st year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the 1st year, immunotherapy was superior.
KW - European Medicines Agency
KW - Food and Drug Administration
KW - Immune checkpoint blockade
KW - Metastatic urothelial cancer
KW - Real-world data
UR - http://www.scopus.com/inward/record.url?scp=85069707419&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2019.07.032
DO - 10.1016/j.eururo.2019.07.032
M3 - Article
C2 - 31362898
AN - SCOPUS:85069707419
SN - 0302-2838
VL - 76
SP - 524
EP - 532
JO - European Urology
JF - European Urology
IS - 4
ER -