Analysis from a phase III trial confirmed the prognostic value of a 16-gene recurrence score (RS) in patients with high-risk renal cell carcinoma (RCC) undergoing adjuvant sunitinib therapy. Though the score cannot yet be used to select patients for adjuvant therapy, it could be used to identify those who will derive the greatest benefit.
Risk assessment in RCC is currently done using models such as the UCLA Integrated Staging System and the Mayo Clinic System (known as the Leibovich Score). “The markers we actually use do not capture the underlying tumor biology, and certainly do not adequately discriminate the recurrence risk,” said Bernard J. Escudier, MD, of Gustave Roussy Cancer Campus in France. “The addition of a prognostic gene expression signature may facilitate the identification of patients with high risk of recurrence.”
Escudier presented results of an analysis (abstract 4508) testing a previously developed 16-gene RS during the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, held June 2–6 in Chicago. The study included a total evaluable population of 193 patients with high-risk, stage III RCC included in the S-TRAC study; 90 patients were treated with placebo, and 103 were treated with sunitinib.
In the placebo patients, each 25-unit increase in RS was associated with a hazard ratio (HR) for recurrence of 4.24 (95% CI, 2.31–7.80; P < .0001). In sunitinib patients, the HR per 25-unit increase in the score was 2.53 (95% CI, 1.29–4.97; P = .008). Escudier noted that a small total number of recurrences (63 in total) provided low power for an interaction test.
The investigators also divided patients into low-, intermediate-, and high-risk groups based on RS. Compared with the low-risk group, the high-risk group who received placebo had an HR for recurrence of 9.18 (95% CI, 2.15–39.24; P < .001). In the sunitinib patients, this HR was 1.86 (95% CI, 0.68–5.06; P = .20).
With regard to disease-free survival, the HR per 25-unit increase in RS was 3.75 (95% CI, 2.13–6.60; P < .001) for placebo, and 2.31 (95% CI, 1.20–4.43; P = .014) for sunitinib. For renal cancer–specific survival, the HR for placebo patients was 7.21 (95% CI, 2.85–18.21; P < .001), and for sunitinib patients it was 3.33 (95% CI, 1.48–7.49; P = .005).
Escudier concluded that the associations between the RS and time to recurrence, disease-free survival, and renal cancer–specific survival confirm the prognostic value of this assay, though its predictive value to select patients for adjuvant sunitinib therapy has not been demonstrated. “Our RS score results may help identify patients with clear-cell stage III RCC which could benefit from adjuvant treatment, especially sunitinib, if this drug is approved in this setting here.”
Daniel Y. C. Heng, MD, MPH, of the Tom Baker Cancer Centre in Calgary, Canada, was the discussant for the session, and agreed that the RS is now externally validated. He pointed out that this analysis included only 34% of the patients in the S-TRAC trial, because most did not have tissue available for analysis. Clinicians, he said, “should encourage patients and investigators to donate tissue to important causes like this.”