Abstract
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).
Keywords
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Article Info
Publication History
Published online: May 04, 2022
Accepted:
April 29,
2022
Received in revised form:
April 27,
2022
Received:
April 13,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
