In a National Cancer Institute phase II trial reported in The New England Journal of Medicine, Srinivasan et al investigated whether the monoclonal antibody bevacizumab in combination with the EGFR inhibitor erlotinib showed activity in patients with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) and sporadic papillary kidney cancer.
Study Details
In the open-label trial, 43 patients with HLRCC-associated papillary renal cell carcinoma and 40 patients with sporadic papillary renal cell carcinoma were enrolled between May 2010 and May 2019. Patients received bevacizumab at 10 mg/kg every 2 weeks and erlotinib at 150 mg once daily in 28-day cycles. The primary outcome measure was objective response.
Key Findings
Median follow-up was 71.9 months in the HLRCC-associated papillary renal cell carcinoma group and 63.6 months in the sporadic papillary renal cell carcinoma group.
In the HLRCC-associated papillary renal cell carcinoma group, objective responses were observed in 31 patients (72%, 95% confidence interval [CI] = 57%–83%), with complete response in 2 patients (5%). Median duration of response was 19.3 months (95% CI = 12.9–35.9 months). Median progression-free survival was 21.1 months (95% CI = 15.6–26.6 months). Median overall survival was 44.6 months (95% CI = 32.7 months to not estimable).
In the sporadic papillary renal cell carcinoma group, objective responses (all partial) were observed in 14 patients (35%, 95% CI = 22%–51%). Median duration of response was 18.4 months (95% CI = 13.8–49.7 months). Median progression-free survival was 8.9 months (95% CI = 5.5–18.3 months). Median overall survival was 18.2 months (95% CI = 12.6–29.3 months).
The most common treatment-related adverse events of any grade among all patients were acneiform rash (93%), diarrhea (89%), and proteinuria (78%). Treatment-related adverse events of grade ≥ 3 occurred in 52% of patients, most commonly hypertension (34%), proteinuria (17%), diarrhea (5%), and acneiform rash (5%). Adverse events led to the discontinuation of bevacizumab in three patients and erlotinib in one patient.
The investigators concluded: “The combination of bevacizumab and erlotinib showed antitumor activity in patients with HLRCC-associated or sporadic papillary renal cell carcinoma. Toxic effects were those known to be associated with this combination.”
Ramaprasad Srinivasan, MD, PhD, of the Center for Cancer Research, National Cancer Institute, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the National Cancer Institute and others. For full disclosures of all study authors, visit The New England Journal of Medicine.
