Abstract
BackgroundAntibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). This phase Ib cohort of the JAVELIN Solid Tumor trial assessed the efficacy and safety of avelumab (anti–PD-L1) monotherapy in patients with mRCC as either first-line (1 L) or second-line (2 L) treatment.MethodsPatients with mRCC with a clear-cell component who were treatment naive (1 L subgroup) or had disease progression after one prior line of therapy (2 L subgroup) received avelumab 10 mg/kg intravenous infusion every 2 weeks. Endpoints included confirmed best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), PD-L1 expression, and safety.ResultsA total of 62 patients were enrolled in the 1 L subgroup, and 20 patients were enrolled in the 2 L subgroup. In the 1 L and 2 L subgroups, confirmed objective response rates were 16.1 and 10.0%, median DOR was 9.9 months (95% confidence interval [CI], 2.8–not evaluable) and not evaluable (95% CI, 6.9–not evaluable), median PFS was 8.3 months (95% CI, 5.5–9.5) and 5.6 months (95% CI, 2.3–9.6), and median OS was not evaluable (95% CI, not evaluable) and 16.9 months (95% CI, 8.3–not evaluable), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 51 patients in the 1 L subgroup (82.3%) and 14 patients in the 2 L subgroup (70.0%). Grade ≥ 3 TRAEs occurred in eight patients in the 1 L subgroup (12.9%) and one patient in the 2 L subgroup (5.0%). No treatment-related deaths occurred.ConclusionAvelumab showed clinical activity and a manageable safety profile in both the 1 L and 2 L treatment setting in patients with mRCC. These data support the use of avelumab in combination with other agents in mRCC.Trial registrationClinicalTrials.gov: NCT01772004; registered 21 January, 2013.
Highlights
Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma
Progress has been made in the treatment of advanced or metastatic Renal cell carcinoma (RCC) and multiple targeted therapies have been approved, including tyrosine kinase inhibitors (TKIs), mammalian target of rapamycin inhibitors), and the anti– vascular endothelial growth factor antibody bevacizumab in combination with interferon alpha [5]
These targeted therapies have shown clinical activity and prolonged survival in patients with metastatic renal cell carcinoma (mRCC) [6]; responses are generally short-lived, development of treatment resistance is common [5, 7], and different classes of targeted therapy are associated with characteristic toxicity profiles that have implications for patient treatment selection [5]
Summary
Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). Progress has been made in the treatment of advanced or metastatic RCC and multiple targeted therapies have been approved, including tyrosine kinase inhibitors (TKIs), mammalian target of rapamycin inhibitors), and the anti– vascular endothelial growth factor antibody bevacizumab in combination with interferon alpha [5] These targeted therapies have shown clinical activity and prolonged survival in patients with mRCC [6]; responses are generally short-lived, development of treatment resistance is common [5, 7], and different classes of targeted therapy are associated with characteristic toxicity profiles that have implications for patient treatment selection [5]. Nivolumab in combination with ipilimumab (anti–cytotoxic T-lymphocyte protein 4) was approved for patients with previously untreated, intermediate- or poor-risk, advanced RCC, based on OS data from the phase III CheckMate 214 trial of nivolumab plus ipilimumab compared with sunitinib [14]
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