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A Phase II, Single-arm Trial of Sunitinib and Erlotinib in Advanced Renal Cell Carcinoma
Zizhen Feng1, Brendan D Curti2, David I Quinn3
1Oregon Health and Science University Knight Cancer Institute, Portland, OR.
Background:
Overexpression of the epidermal growth factor receptor (EGFR) and its ligands occur frequently in renal cell carcinoma (RCC). Combined vascular endothelial growth factor receptor (VEGF-R) and EGFR inhibition may overcome resistance to VEGF-R inhibitor monotherapy. We performed a dose-escalation phase II study of sunitinib plus erlotinib in advanced renal cell carcinoma.
Patients And Methods:
Patients with metastatic clear cell or papillary RCC were eligible. Prior therapy was allowed except sunitinib or erlotinib. Three dose levels of erlotinib (50, 100, 150 mg daily) were evaluated in combination with sunitinib 50 mg. Thirty-seven patients were treated at maximum tolerated dose to determine efficacy. The primary endpoint was 8-month progression-free survival (PFS) rate. The trial was powered to assess for a difference between a median PFS of less than 50% with a targeted 70% PFS for the combination.
Results:
The 8-month PFS rate was 40% (95% CI: 23-56). Median PFS was 5.8 months (95% CI: 4.1-9.7) and median overall survival (OS) was 26.3 months (95% CI: 16.1-34.0). The objective response rate was 22% and an additional 59% of patients had stable disease for at least 6 weeks. The most common adverse events for all grades were diarrhea, rash, fatigue, and dysgeusia. Dose reduction in 1 or both of the drugs was undertaken in 17 (46%) patients, while 5 (14%) discontinued study therapy due to toxicity.
Conclusion:
While sunitinib and erlotinib are combinable,the 8-month PFS rate did not suggest efficacy improvement over sunitinib monotherapy (NCT00425386).
Insights
Combining sunitinib with erlotinib did not improve progression-free survival in advanced renal cell carcinoma (RCC) patients. The 8-month PFS rate was 40%, indicating no significant efficacy benefit over sunitinib alone.
Area of Science:
- Oncology
- Medical Research
Background:
- Renal cell carcinoma (RCC) frequently exhibits overexpression of epidermal growth factor receptor (EGFR) and its ligands.
- Combined inhibition of vascular endothelial growth factor receptor (VEGF-R) and EGFR may overcome resistance to VEGF-R inhibitor monotherapy.
Purpose of the Study:
- To evaluate the efficacy and safety of combining sunitinib with erlotinib in advanced renal cell carcinoma.
- To determine if this combination therapy improves progression-free survival compared to monotherapy.
Main Methods:
- A dose-escalation phase II study was conducted involving patients with metastatic clear cell or papillary RCC.
- Patients received sunitinib (50 mg daily) combined with escalating doses of erlotinib (50, 100, or 150 mg daily).
- The primary endpoint was the 8-month progression-free survival (PFS) rate, with a target of 70%.
Main Results:
- The 8-month PFS rate was 40% (95% CI: 23-56), falling short of the target.
- Median PFS was 5.8 months, and median overall survival (OS) was 26.3 months.
- The objective response rate was 22%, with 59% experiencing stable disease; common adverse events included diarrhea and rash.
Conclusions:
- Sunitinib and erlotinib are combinable in advanced RCC.
- The combination did not demonstrate improved efficacy over sunitinib monotherapy based on the 8-month PFS rate.
