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The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.
More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.
The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.
“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.
The study, known as JAVELIN Renal 100, was a phase 1b investigation that included 55 patients with advanced clear-cell RCC. A total of 6 patients were enrolled in a smaller dose-finding cohort, and 49 were enrolled in a dose-expansion cohort.
In the dose-finding phase, patients received oral axitinib 5 mg twice a day for 7 days, at which point they started intravenous avelumab 10 mg/kg every 2 weeks, according to the study description. In the dose-expansion phase, patients were directly started on the combination.
Out of 55 patients enrolled, 26 (53%) had a response on the axitinib-avelumab combination, including 3 (6%) who had complete responses, investigators reported.
Grade 3 or greater treatment-related adverse events were reported in 32 patients (58%). The most common of those was hypertension, occurring in 16 patients (29%), followed by ALT increase and palmar-plantar erythrodysesthesia syndrome in 4 patients each (7%), Dr. Choueiri and colleagues wrote.
In the dose-finding phase, investigators reported one dose-limiting toxicity, which was grade 3 proteinuria due to axitinib.
. In that randomized trial, the axitinib-avelumab combination is being compared to sunitinib as a first-line approach in patients with advanced RCC.
“The combination of an antibody that inhibits PD-L1 and PD-1 interactions with a targeted antiangiogenic agent might take advantage of complementary mechanisms of action to provide clinical benefit in patients with advanced renal-cell carcinoma that exceeds the effects of the respective drugs alone without increasing associated toxicity,” Dr. Choueiri and colleagues wrote.
Pfizer and Merck funded the study. Dr. Choueiri declared interests related to several companies, including AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, Peloton, and Roche/Genentech.
SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.
The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.
More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.
The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.
“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.
The study, known as JAVELIN Renal 100, was a phase 1b investigation that included 55 patients with advanced clear-cell RCC. A total of 6 patients were enrolled in a smaller dose-finding cohort, and 49 were enrolled in a dose-expansion cohort.
In the dose-finding phase, patients received oral axitinib 5 mg twice a day for 7 days, at which point they started intravenous avelumab 10 mg/kg every 2 weeks, according to the study description. In the dose-expansion phase, patients were directly started on the combination.
Out of 55 patients enrolled, 26 (53%) had a response on the axitinib-avelumab combination, including 3 (6%) who had complete responses, investigators reported.
Grade 3 or greater treatment-related adverse events were reported in 32 patients (58%). The most common of those was hypertension, occurring in 16 patients (29%), followed by ALT increase and palmar-plantar erythrodysesthesia syndrome in 4 patients each (7%), Dr. Choueiri and colleagues wrote.
In the dose-finding phase, investigators reported one dose-limiting toxicity, which was grade 3 proteinuria due to axitinib.
. In that randomized trial, the axitinib-avelumab combination is being compared to sunitinib as a first-line approach in patients with advanced RCC.
“The combination of an antibody that inhibits PD-L1 and PD-1 interactions with a targeted antiangiogenic agent might take advantage of complementary mechanisms of action to provide clinical benefit in patients with advanced renal-cell carcinoma that exceeds the effects of the respective drugs alone without increasing associated toxicity,” Dr. Choueiri and colleagues wrote.
Pfizer and Merck funded the study. Dr. Choueiri declared interests related to several companies, including AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, Peloton, and Roche/Genentech.
SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.
The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.
More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.
The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.
“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.
The study, known as JAVELIN Renal 100, was a phase 1b investigation that included 55 patients with advanced clear-cell RCC. A total of 6 patients were enrolled in a smaller dose-finding cohort, and 49 were enrolled in a dose-expansion cohort.
In the dose-finding phase, patients received oral axitinib 5 mg twice a day for 7 days, at which point they started intravenous avelumab 10 mg/kg every 2 weeks, according to the study description. In the dose-expansion phase, patients were directly started on the combination.
Out of 55 patients enrolled, 26 (53%) had a response on the axitinib-avelumab combination, including 3 (6%) who had complete responses, investigators reported.
Grade 3 or greater treatment-related adverse events were reported in 32 patients (58%). The most common of those was hypertension, occurring in 16 patients (29%), followed by ALT increase and palmar-plantar erythrodysesthesia syndrome in 4 patients each (7%), Dr. Choueiri and colleagues wrote.
In the dose-finding phase, investigators reported one dose-limiting toxicity, which was grade 3 proteinuria due to axitinib.
. In that randomized trial, the axitinib-avelumab combination is being compared to sunitinib as a first-line approach in patients with advanced RCC.
“The combination of an antibody that inhibits PD-L1 and PD-1 interactions with a targeted antiangiogenic agent might take advantage of complementary mechanisms of action to provide clinical benefit in patients with advanced renal-cell carcinoma that exceeds the effects of the respective drugs alone without increasing associated toxicity,” Dr. Choueiri and colleagues wrote.
Pfizer and Merck funded the study. Dr. Choueiri declared interests related to several companies, including AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, Peloton, and Roche/Genentech.
SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.
FROM THE LANCET ONCOLOGY
Key clinical point: The targeted-immune combination of axitinib and avelumab had manageable toxicity and encouraging preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC).
Major finding: Out of 55 patients enrolled, 26 (53%) had a response, including 3 (6%) who had complete responses.
Study details: A dose-expansion and dose-finding phase 1b study including 55 patients with advanced clear-cell RCC.
Disclosures: Funding for the study came from Pfizer and Merck. Study authors declared interests related to several companies, including Pfizer, Merck, Bristol-Myers Squibb, Novartis, Roche/Genentech.
Source: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.
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The antitumor activity of axitinib and avelumab in this study indicate the potential clinical benefit of targeted-immune combinations for advanced renal cell carcinoma (RCC), according to Viktor Grünwald, MD, PhD.
“Further studies are warranted to explore whether a first-line targeted-immune combination might overcome the standard of sequential targeted and immune therapies,” Dr. Grünwald said in an editorial.
The current absence of long-term safety data for the combination approach is limiting in terms of making definitive conclusions about the toxicity of axitinib and avelumab as a first line combination therapy for advanced clear-cell RCC, Dr. Grünwald wrote.
Even so, axitinib has a “low” incidence of hepatic toxicity, making it a “preferable” agent to evaluate in targeted-immune combination trials such as JAVELIN Renal 100, he added.
Objective responses in JAVELIN Renal 100 were seen in 32 out of 55 patients (58%), of which 3 patients (6%) were complete responses, according to reported data.
Similar findings previously reported for the immune-immune combination of ipilimumab and nivolumab versus sunitinib. In that study, patients receiving the immune-immune combination had an overall response rate of 42% and complete response rate of 9%, while the group patients receiving sunitinib had overall and complete response rates of 27% and 1%, respectively, he said.
“With the dawn of immune-immune and targeted-immune combinations, for the first time in a decade, major progress towards improving the median overall survival and possibly delivering cure to some of our patients with metastatic renal-cell carcinoma seems to have been made,” Dr. Grünwald said.
Viktor Grünwald, MD, PhD, is with the department of hematology, haemostasis, oncology, and stem cell transplantation at Hannover Medical School, Germany. These comments are based on an editorial accompanying the report (Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045[18]30126-8). Dr. Grünwald disclosed ties to Bristol-Myers Squibb, Merck Sharp and Dohme, Ipsen, Novartis, Roche, AstraZeneca, Pfizer, Cerulean, Eisai, and EUSA Pharma.