Immunotherapy plus sunitinib doubles survival in unfavorable-risk mRCC
Autologous dentritic cell immunotherapy (AGS-003) in combination with sunitinib nearly doubled overall survival (OS) in patients with unfavorable-risk metastatic renal cell carcinoma (mRCC) in a single-arm phase II study.
“While targeted therapies have yielded improved efficacy in treatment of advanced RCC, durable remissions are rare, particularly in unfavorable-risk subjects,” said lead author Dr. Asim Amin of the Carolinas Medical Center and Blumenthal Cancer Center in Charlotte, USA. “In a pivotal trial, sunitinib treatment yielded a median OS of 5.3 months for poor-risk patients and 20.7 months for intermediate-risk patients. Similarly, the validation dataset for the Heng risk model showed a median OS of 8 months for poor-risk and 21 months for intermediate-risk patients treated with VEGF targeted therapies.”
As immunotherapy has shown durable responses in RCC, Amin and colleagues treated 21 patients with poor- and intermediate-risk mRCC with standard 6-week cycles of sunitinib plus AGS-003 (once every 3 weeks x 5 doses, then every 12 weeks until disease progression) and followed them for progression-free survival (PFS) and OS. [Abstract 357]
In the study, tumor response was assessed based on the response evaluation criteria in solid tumors (RECIST). Samples for immune monitoring were taken at screening, baseline, and after the third and fifth doses of AGS-003, and analyzed by multiparametric flow cytometry.
“As reported previously, median PFS was 11.2 months, and the final median OS was 30.2 months,” Amin reported. “When analyzed by baseline Heng risk status, median PFS was 19.4 months for patients with intermediate risk [n=11] and 5.8 months for those with poor risk [n=10]. Median OS was >39.5 months for intermediate-risk patients, and 9.1 months for poor-risk patients. Eight of 21 patients are still alive and continue to be followed.”
“This novel combination therapy using patient-specific immunotherapy plus an oral agent showed significant benefits with a doubling of survival in patients with aggressive mRCC. This is very encouraging and will need to be confirmed in a larger number of patients,” commented Dr. Leonard Gomella of the US Society of Urologic Oncology.
According to Amin, a phase III trial is ongoing to validate the initial clinical and immunologic findings.