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 - Funding Information:
Financial disclosures: Emily Feld certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Ronac Mamtani has served as a consultant for Roche/Genentech. Rebecca A. Hubbard has received research funding from Humana. Neal J. Meropol, Blythe J.S. Adamson, and Aaron Cohen report employment at Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. John Christodouleas reports part-time employment at Elekta, Inc.
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 -