Daniel J. George, MD
Findings from the phase III S-TRAC trial led to the FDA approval of sunitinib (Sutent) in November 2017 as an adjuvant therapy for patients with renal cell carcinoma (RCC) who are at high risk for recurrence. In a prospective study presented at the 2018 ASCO Annual Meeting, Daniel J. George, MD, reported on the disease-free survival (DFS) of patients at the highest risk of recurrence from S-TRAC.1
DFS analyses showed that the treatment benefit by independent review for sunitinib versus placebo in this group (HR, 0.73; 95% CI, 0.54-0.97; P
= .03) was consistent with the hazard ratio previously reported in the S-TRAC trial for patients with T3 or higher disease. The hazard ratio for T3 or higher was (HR, 0.74; 95% CI, 0.55-0.99; P
George said that these findings, paired with a consistent safety profile between the groups, support the assessment of sunitinib as a viable adjuvant treatment option for patients with RCC who are at high risk of recurrence following nephrectomy.
In another analysis on S-TRAC presented at the 2018 ASCO Annual Meeting, investigators evaluated neutrophil-to-lymphocyte ratio as a prognostic factor of DFS in patients with high-risk RCC.2
George said that a lower neutrophil-to-lymphocyte ratio may be a prognostic factor of shorter DFS.
In an interview with OncLive
, George, professor of Medicine at Duke Cancer Center, discussed the analysis of RCC patients in the S-TRAC trial with the highest risk of recurrence, and potential prognostic factors of DFS that emerged from the study.
OncLive: Can you share some background on the rationale for the S-TRAC study?
S-TRAC was a phase III, prospective, multicenter study looking at the effectiveness of sunitinib versus placebo in patients at high risk for disease recurrence, particularly T3 or node-positive kidney cancer. In that prospective study, what we found [in the overall population] was that treatment with sunitinib for up to 1 year delayed DFS by about 24% with a hazard ratio of 0.76 and a P
value of .03. This was a 615-patient study.
We wanted to look at higher-risk patients because these patients are more likely to relapse sooner, and because those at higher risk may benefit by a greater proportion to adjuvant therapy. We identified high-risk as patients with T3 or higher grade, node-positive T4, or a decreased performance status of 1 or less. In those subgroups, we saw a greater overall benefit associated with 1 year of sunitinib with a hazard ratio of 0.73, so a 27% reduction in the risk of disease recurrence. Like the overall population, that was a sustained benefit up to 5 years or more.
As we enrich for patients at greater risk for disease recurrence, the benefit of sunitinib doesn't go away—if anything, it increases. To me, it reinforces that in our high-risk patients, particularly those T4 node-positive patients, we see a benefit. Even though those numbers are decreased, the statistical significance was sustained. That is really important.
What is the significance of these findings?
Clinically, when we are thinking about who to treat with sunitinib, we want to pick the patients who we think are most likely to benefit. By enriching for these highest-risk patients, we can focus further on the patients wo are most likely to benefit. When I see a patient in my clinic who has node-positive disease, T4 disease, or poor-performance status, that is going to be a patient who I am more inclined to offer sunitinib to, even if I think they might be on the fence medically. This means that they are older, or have other issues that question whether they can tolerate sunitinib for 1 year. That is a patient who I still want to have a conversation with, because there is a greater risk of them recurring and a greater benefit associated with that adjuvant therapy.
Were these findings expected?
[It was only expected in] that this is consistent with the overall population. We are not saying that this is the only subset that is benefitting—we are seeing the overall population benefit—but we are seeing an enrichment in the higher-risk patients. We're not pigeonholing the drug to only those patients, we are saying especially
in those patients.