Based on data from the phase III S-TRAC trial,<span style="font-size:10.8333px"> </span>the European Medicines Agency’s Committee for Medicinal Products for Human Use recently recommended against approving sunitinib for use as an adjuvant therapy in patients with renal cell carcinoma who have received nephrectomy and are high risk for recurrence.
Mace Rothenberg, MD
Based on data from the phase III S-TRAC trial,1,2the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recently recommended against approving sunitinib (Sutent) for use as an adjuvant therapy in patients with renal cell carcinoma (RCC) who have received nephrectomy and are high risk for recurrence.
The CHMP opinion will now be reviewed by the European Commission for a final regulatory decision.
In results from the S-TRAC trial, adjuvant sunitinib prolonged disease-free survival (DFS) by 1.2 years compared with placebo following nephrectomy for patients with high-risk clear cell RCC.
“We remain confident in the potential of Sutent for RCC patients at high risk of their cancer returning after surgery who today are restricted to a wait and see, or more accurately, a wait and worry approach,” Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development, said in a statement. “We will continue to work closely with the European Medicines Agency as they complete their review and render a decision on this application.”
The S-TRAC study randomized 615 patients with clear cell RCC to receive sunitinib (n = 309) or placebo (n = 306). Patient characteristics were well balanced between the arms. The median age of patients in the sunitinib arm was 57 years, and most were males (71.8%). Most patients had an ECOG performance score of 0 (73.8%).
Overall, 90.6% of those in the sunitinib arm had a stage 3 tumor, with no nodal involvement and no metastasis. Of these patients, 37.2% were considered low-risk (any Fuhrman grade and ECOG score of 0 or Fuhrman grade 1 and ECOG score of ≥1) and 53.4% were high-risk (Fuhrman grade ≥2 and ECOG score of ≥1).
Sunitinib was administered at 50 mg daily for 4 weeks followed by 2 weeks without treatment. One dose reduction was allowed in the study, to 37.5 mg per day. Overall, more than half of patients (54.2%) were able to maintain treatment with the starting dose of 50 mg per day. The median daily dose was 45.9 mg.
After a median follow-up duration of 5.4 years, the median DFS was 6.8 years in the sunitinib arm compared with 5.6 years with placebo (HR, 0.76; 95% CI, 0.59-0.98;P= .03). In higher risk patients, the median DFS was 6.2 versus 4.0 years for sunitinib and placebo, respectively (HR, 0.74; 95% CI, 0.55-0.99; P= .04). Grade 3/4 adverse events (AEs) were experienced by 63.4% of patients in the sunitinib group compared with 21.7% in the placebo arm.
After 3 years, 64.9% of those in the sunitinib group were alive and remained disease-free compared with 59.5% in the placebo arm. At 5 years, the DFS rate was 59.3% with sunitinib versus 51.3% for placebo. Median overall survival findings were not yet mature at the time of the analysis; however, the hazard ratio between the two arms for survival was 1.01 (95% CI, 0.72-1.44;P= .94).
The investigator assessed median DFS in the sunitinib arm was 6.5 years compared with 4.5 years with placebo (HR, 0.81; 95% CI, 0.64-1.02;P= .08). In higher risk patients, the median DFS by investigator assessment was 5.9 versus 3.9 years for sunitinib and placebo, respectively (HR, 0.76; 95% CI, 0.58-1.01; P= .06).
Treatment-emergent AEs were experienced by 99.7% of patients treated with sunitinib versus 88.5% in the placebo arm. Treatment-emergent AEs by investigator assessment occurred in 98.4% of those treated with sunitinib versus 75.7% with placebo. AEs led to discontinuation for 28.1% of patients in the sunitinib arm versus 5.6% of those in the placebo group.
The most common AEs in the sunitinib arm were diarrhea (56.9%), palmarplantar erythrodysesthesia (50.3%), hypertension (36.9%), fatigue (36.9%), and nausea (34.3%). The most common grade 3/4 AEs were palmar–plantar erythrodysesthesia (16%), neutropenia (8.5%), hypertension (7.8%), and thrombocytopenia (6.2%). The rate of serious adverse events AEs was similar for sunitinib (21.9%) versus placebo (17.1%).