Effectiveness of First-Line Immunotherapy for Metastatic Melanoma: A Propensity Score Analysis from the Texas Cancer Registry Database
Introduction
The last decade saw the expansion of immunotherapy, notably immune checkpoint inhibitors (ICIs), for treating metastatic melanoma due to their demonstrated success in clinical trials. These agents are now approved by the Food and Drug Administration (FDA) and are recommended for use by the National Comprehensive Cancer Network (NCCN) in patients with metastatic melanoma. The objective of this study was to determine the use of first-line immunotherapy agents for metastatic melanoma and to evaluate associated survival benefits in the era of ICIs.
Methods
A retrospective analysis involving 1,372 patients with metastatic melanoma who received treatment from 2011 to 2018 (post-FDA approval of ICIs) as identified from the Texas Cancer Registry (TCR) database. The main exposure was metastatic melanoma diagnosis. The outcomes examined were overall survival (OS) and cause-specific survival (CSS). Kaplan-Meier analysis was used to characterize the unadjusted OS and CSS of patients who received immunotherapy as first-line agents (treatment group) and those who received other treatments (alternative treatment group). Propensity score (PS) analysis using inverse probability treatment weighting (IPTW) was used to balance measured baseline covariates between the two groups. The effect of immunotherapy as first-course therapy on OS and CSS was then assessed with a PS-adjusted Cox proportional hazard model. To assess the robustness of our findings, analyses were repeated using regression adjustment, PS matching to adjust for covariates, and testing for informative censoring and immortal time bias using landmark analysis.
Results
Of the 1,372 patients with metastatic melanoma, 429 (31.30%) received immunotherapy. Immunotherapy group was younger [Median (Q1-Q3): 62 (52-71) vs 65 (55-76) years]. The median (IQR) follow-up time for the cohort was 67.2 (39.61-98.47) months. IPTW balanced baseline characteristics across comparison groups (standardized mean difference <±0.25). Patients receiving immunotherapy had significantly longer median (interquartile range) survival [CSS: 27.00 (21.00-42.00) months versus 16.00 (14.00-19.00) months; OS: 22.00 (17.00-27.00) months versus 12.00 (11.00-14.00) months] and reduced mortality risk (HR for CSS: 0.80; 95%CI: 0.73-0.88; p<0.0001; HR for OS: 0.76; 95%CI: 0.69-0.83; p<0.0001). Results of the sensitivity analyses corroborated our main findings.
Conclusion
Immunotherapy utilization as first-course therapy for metastatic melanoma was associated with improved survival in the Texan population. We added to previous studies by generating robust evidence to support immunotherapy effectiveness using real-world data. The proportion of patients receiving first-line immunotherapy was, however, low, suggesting the need for efforts to improve their adoption in clinical practice.