Hematology/Oncology Fellow Memorial Sloan Kettering Cancer Center New York, NY, United States
Background: First-line treatment options for clear cell renal cell carcinoma (ccRCC) include ipilimumab with nivolumab (IO/IO) or several VEGFR-targeted therapies in combination with a PD-1 inhibitor (TKI/IO). Depth of response (DpR) has been proposed as a predicter of sustained benefit from IO-based therapies. Here, we examine the relationship between DpR and OS in patients receiving 1st line IO/IO vs TKI/IO for metastatic ccRCC.
Methods: A retrospective analysis was performed on patients treated for ccRCC with 1st line IO/IO or TKI/IO at MSKCC between 1/1/2014 and 12/30/2020. DpR is defined as the nadir of tumor shrinkage by RECIST 1.1 criteria. Partial response groups were defined as PR1 (80-99%), PR2 (60-79%), and PR3 (30-59%). Overall survival (OS) from start of 1st line therapy to death or last follow-up is estimated with the Kaplan-Meier method and reported for each DpR group.
Results: One hundred seventy-three patients received 1st line IO/IO (N=90) or TKI/IO (N=83). Differences in the IO/IO group versus TKI/IO include more patients with brain metastases (9% vs 0, p=0.007) and intermediate-poor IMDC risk (88% vs 68%, p=0.007), and fewer with prior nephrectomy (67% vs 86%, p=0.005). Objective response rates for IO/IO and TKI/IO groups were respectively 38% (95% CI: 28, 49) and 65% (95% CI: 54, 75; P< 0.001). Patient distribution across response groups is shown in Table 1; the difference in distribution was significantly different between IO/IO and TKI/IO treatment groups; P=0.002. Twenty four-month survival estimates for response groups are shown in Table 1.
Conclusions: Patients receiving first-line IO/IO or TKI/IO therapies had a significant difference in the distribution of radiographic DpR groups, with more CR and PR seen in the TKI/IO group and more SD and PD seen with IO/IO. Patients whose best response was CR, PR1, or PR2 had higher 24-month OS than patients with PR3, SD, or PD.
