Utilization and sequencing of targeted therapy and cytoreductive nephrectomy in non–clear cell metastatic kidney cancer.
615 Background: Many patients with metastatic kidney cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age < 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results: Of 1,326 mRCC cases, 528 met inclusion criteria of whom 433 (82%) received targeted agents and 172 (33%) underwent CN. Of those not having CN, 74% were diagnosed by biopsy, 10% by cytology, and 16% radiographically (confirmed at autopsy). Thirteen percent received CN then targeted therapy (OS 14 mos, IQR 9-25), 2.5% received targeted therapy then CN (OS 14 mos, IQR 9-26), 18% received CN only (OS 14 mos, IQR5-40), 67% received targeted therapy only (OS 9 mos, IQR 4-19). On multivariable Cox proportional hazards regression upfront CN (regardless of post-CN therapy) was associated with improved OS (HR 0.54,95% CI 0.41,0.72). Using propensity scores, upfront CN patients (N = 161) were matched to upfront targeted therapy patient (N = 111) and the average treatment effect of CN was 8.3 months survival improvement (95% CI 4.0, 13.2). Conclusions: Although utilization of targeted agents in non-clear cell mRCC exceeds 80%, those with greatest OS received CN either upfront or after targeted therapy, though the latter was rare (2.5%). The variety of sequencing strategies observed is evidence of uncertainty regarding the best care for non-clear cell mRCC patients given limited options.