In a real-world retrospective propensity-matched cohort study reported in JAMA Network Open, Chakiryan et al found that both first-line immunotherapy and combined treatment with targeted therapy plus immunotherapy were associated with improved overall survival vs targeted therapy alone in patients with metastatic clear cell renal cell carcinoma (RCC), supporting findings made in comparative clinical trials.
As stated by the investigators, “Clinical trials have shown an overall survival benefit associated with first-line immunotherapy and combination targeted therapy and immunotherapy regimens compared with targeted therapy among patients with metastatic clear cell RCC. Generalizability of these findings in a real-world cohort outside of a clinical trial setting is unclear.”
Study Details
The study included 5,872 patients with metastatic clear cell RCC in the National Cancer Database from January 2015 to December 2017 who received first-line targeted therapy (n = 4,755), immunotherapy (n = 638), or targeted therapy plus immunotherapy (n = 479). Propensity score-matching was performed for each patient in the targeted therapy plus immunotherapy group with a counterpart from each of the other two groups. The post-matching population consisted of 1,437 patients, with 479 in each group. The primary outcome measure was overall survival from date of diagnosis to death or censoring at last follow-up. Bonferroni correction was used to account for multiple comparisons, with P = .0167 defined as significant.
This study suggests that both first-line immunotherapy and combination targeted therapy and immunotherapy were associated with improved overall survival compared with first-line targeted therapy for patients with metastatic clear cell RCC.— Chakiryan et al
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Key Findings
Since none of the post-matching patient or tumor demographic variables exhibited differences between groups with P ≤ .10, a univariate Cox proportional hazards regression was performed as the primary outcome. This analysis showed that both immunotherapy alone (hazard ratio [HR]= 0.60, 95% confidence interval [CI] = 0.48–0.75, P < .001) and targeted therapy plus immunotherapy (HR = 0.74, 95% CI = 0.60–0.91, P = .005) were associated with significantly improved overall survival vs targeted therapy alone. Compared with the immunotherapy alone group, overall survival was not significantly poorer in the targeted therapy plus immunotherapy group (HR = 1.24, 95% CI = 0.98–1.56, P = .08).
In a sensitivity analysis, a multivariate Cox proportional hazards regression was performed including all patient and tumor demographic variables as covariates. In this analysis, both immunotherapy alone (HR = 0.70, 95% CI = 0.57–0.91, P = .006) and immunotherapy plus targeted therapy (HR = 0.76, 95% CI = 0.61–0.94, P = .01) were associated with significantly improved overall survival vs targeted therapy alone. No significant difference was observed for immunotherapy plus targeted therapy vs immunotherapy alone (HR = 1.06, 95% CI = 0.85–1.36, P = .60).
On Kaplan-Meier analysis, 12-month overall survival was 73% in the immunotherapy group, 68% in the immunotherapy plus targeted therapy group, and 59% in the targeted therapy group.
The investigators concluded, “This study suggests that both first-line immunotherapy and combination targeted therapy and immunotherapy were associated with improved overall survival compared with first-line targeted therapy for patients with metastatic clear cell RCC. These findings are similar to those identified in recently reported clinical trials, lending confidence to the broader applicability of these findings outside of a clinical trial setting.”
Nicholas H. Chakiryan, MD, of the Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, is the corresponding author for the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
