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Results From a Randomized Phase II Trial of Sunitinib and Gemcitabine or Sunitinib in Advanced Renal Cell Carcinoma
Bradley C Carthon1, Se Eun Kim2, David F McDermott3
1Department of Medicine, Winship Cancer Institute, Emory University, Atlanta, GA.
Introduction:
Sarcomatoid renal cancer (sRCC) patients have poor outcomes. EA1808 evaluated sunitinib and gemcitabine (SG) and sunitinib alone (S) in sRCC in a randomized cooperative group phase II trial (NCT01164228).
Patients And Methods:
Pts were aggregated 1:1 to SG (45 pts) or S (40 pts) using a 2-stage design. sRCC pts with ≤ 1 prior nonvascular endothelial growth factor tyrosine kinase inhibitor were stratified into prognostic groups: good (clear cell, < 20% sarcomatoid, PS 0), intermediate (20%-50% sarcomatoid, PS 0), and poor (nonclear cell or > 50% sarcomatoid or PS 1). The primary endpoint was response rate (RR). For SG, the null RR was 15% and a 30% RR was of interest. For S, a 20% RR was of interest vs. a 5% null rate. Secondary endpoints were progression-free survival, overall survival, and safety.
Results:
Both arms met protocol criteria for stage 2 of accrual. A total of 47 pts were randomized to SG and 40 to S. The SG arm had 9 of 45 evaluable patient responses (RR of 20%; CI = [13%-31%]) not meeting the predetermined threshold for success. The sunitinib arm met its endpoint with 6/37 (RR of 16%; CI = [9%-27%]) evaluable responses. Grade ≥ 3 events were experienced by 36 in the SG arm and 17 in the sunitinib arm CONCLUSIONS: EA1808 was the largest and first randomized cytotoxic trial for sarcomatoid RCC. Sunitinib alone but not the SG met the preset threshold of success. Cytotoxic chemotherapy is only useful in limited clinical scenarios for sRCC.
Insights
Sunitinib alone showed promise in treating sarcomatoid renal cancer (sRCC), meeting its endpoint in a phase II trial. Combination therapy with gemcitabine did not meet success criteria, suggesting limited roles for cytotoxic chemotherapy in sRCC.
Area of Science:
- Oncology
- Nephrology
- Clinical Trials
Background:
- Sarcomatoid renal cancer (sRCC) is an aggressive subtype of kidney cancer with poor patient outcomes.
- Limited randomized trials have investigated treatment options for sRCC, highlighting a need for effective therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of sunitinib alone versus sunitinib plus gemcitabine in patients with sarcomatoid renal cancer.
- To determine if the combination therapy could achieve a higher response rate compared to sunitinib monotherapy.
Main Methods:
- A randomized cooperative group phase II trial (EA1808) involving patients with sRCC.
- Patients were stratified into prognostic groups and randomized 1:1 to receive either sunitinib plus gemcitabine (SG) or sunitinib alone (S).
- Primary endpoint was response rate (RR); secondary endpoints included progression-free survival, overall survival, and safety.
Main Results:
- The sunitinib arm met its primary endpoint with a response rate of 16% (CI [9%-27%]).
- The sunitinib plus gemcitabine arm showed a response rate of 20% (CI [13%-31%]), which did not meet the predetermined threshold for success.
- Higher rates of grade ≥ 3 adverse events were observed in the SG arm (36 patients) compared to the sunitinib arm (17 patients).
Conclusions:
- Sunitinib monotherapy met its preset success threshold in this trial for sarcomatoid renal cancer.
- The combination of sunitinib and gemcitabine did not demonstrate sufficient efficacy to meet its target response rate.
- These findings suggest that cytotoxic chemotherapy may have a limited role in the treatment of sRCC, with sunitinib alone showing more promise.
