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MUNICH – The combination of avelumab and axitinib has dramatically improved SSP compared to standard sunitinib in patients with advanced and untreated renal cell carcinoma, according to the results of the randomized phase 3 study presented at the congress of the European Society of Medical Oncology.
The association also had a favorable safety profile.
"These findings confirm that avelumab and axitinib constitute a new front-line treatment for patients with advanced renal cell carcinoma," said study author . Robert J. Motzer, MD, A medical oncologist and a chair in oncology at the Memorial Sloan Kettering Cancer Center, said at a press conference.
About 65,000 kidney cancer cases are diagnosed each year in the United States. Early treatment usually consists of surgical resection, but since there are few warning signs of the disease, approximately 50% of patients will have metastases at the time of initial diagnosis or after nephrectomy.
Sunitinib (Sutent, Pfizer), a multi-target tyrosine kinase inhibitor, has been a standard treatment for kidney cancer since it was approved by the FDA in 2006.
Several compounds are now similar to sunitinib. One of these is axitinib (Inlyta, Pfizer), a small molecule tyrosine kinase inhibitor approved for the second-line treatment of kidney cancer.
"Axitinib has an advantage over sunitinib in that it has less toxicity, particularly liver toxicity, so it combines better with other drugs," Motzer said.
Inhibitors of immune control points have also become a primary treatment option.
In the JAVELIN Renal 101 trial, Motzer and his colleagues compared the association of axitinib and avelumab (Bavencio; EMD Serono, Pfizer), a fully human monoclonal antibody targeting PD- L1, with sunitinib for the first-line treatment of advanced clear cell renal cells. carcinoma.
The analysis involved 886 patients with an ECOG performance index of 0 or 1 and no previous systemic treatment. All prognostic risk groups were included (21% favorable risk, 62% intermediate risk, 16% low risk, <1% not reported).
The researchers randomized 442 patients on IV avelumab at 10 mg / kg every two weeks, with 5 mg axitinib orally twice daily per 6-week cycle. The other 444 patients received 50 mg of sunitinib daily orally every 4 weeks without interruption.
The primary endpoints included PFS – assessed by independent central blind review – and OS in patients with PD-L1 positive tumors (n = 560), defined by 1% or greater expression on immune cells. . Secondary endpoints included PFS and OS regardless of PD-L1 expression, as well as objective response and safety.
The axitinib-avelumab combination appeared associated with longer median PFS in the subgroup of patients with PD-L1 positive disease (13.8 months vs. 7.2 months, HR = 0). , 61; P <0.001), as well as across the entire cohort, regardless of PD-L1 expression (13.8 months vs. 8.4 months, HR = 0.69; P = 0.0001).
The researchers also reported higher objective response rates in patients assigned to the experimental combination in the two PD-L1 positive subgroups (55.2% vs. 25.5%, stratified OR = 3.73; P <0.0001) and the entire cohort (51.4% vs. 25.7%, stratified OR = 3.09; P <.0001).
Less than 16% of patients experienced events by the data submission deadline. The data relating to SG were therefore not mature.
The safety profiles of axitinib and avelumab appeared to match previous studies on each drug.
"Safety is of paramount importance when evaluating a new combination," Motzer said.
A similar percentage of patients treated with axitinib-avelumab and sunitinib monotherapy had treatment-related grade 3 or greater adverse events (71.2% vs. 71.5%).
The most common grade 3 / grade 4 toxicities were diarrhea (55% vs. 55%) and hypertension (24% vs. 15%). A higher percentage of patients treated with sunitinib had Grade 3 neutropenia (7 vs <1), anemia (5 vs <1) or thrombocytopenia (5 vs <1).
A higher percentage of patients assigned to the association stopped the study drug due to adverse events (22.8% vs. 13.4%). Less than 1% of patients in each treatment group died from treatment toxicity (0.7% for the combination versus 0.2% for sunitinib).
"The results are catchy," Thomas Powles, MD, Oncologist consultant Barts Health NHS Trust in London, said in a press release.
"Response rates are twice the previous standards of care, and unprofessional survival is becoming a very impressive area for a randomized trial," added Powles, who did not participate in the study. 39; study. "This approach consists in immediately giving the combinations of the most active agents; therefore, there is uncertainty as to whether this will result in a survival signal as impressive as that seen with other combinations of immunotherapy. "- Mark Leiser
Reference:
Motzer RJ et al. Abstract LBA6_PR. Presented at: Congress of the European Society of Medical Oncology; October 19-23, 2018; Munich.
Disclosures: Pfizer sponsored the lawsuit, which is part of an alliance between Pfizer and Merck KGaA, based in Darmstadt, Germany. Motzer announces research funding or consulting / consulting positions with Bristol-Myers Squibb, Eisai, Exelixis, Genentech / Roche, GlaxoSmithKline, Incyte, Merck Sharpe & Dohme, Novartis and Pfizer.
MUNICH – The combination of avelumab and axitinib has dramatically improved SSP compared to standard sunitinib in patients with advanced and untreated renal cell carcinoma, according to the results of the randomized phase 3 study presented at the congress of the European Society of Medical Oncology.
The association also had a favorable safety profile.
"These findings confirm that avelumab and axitinib constitute a new front-line treatment for patients with advanced renal cell carcinoma," said study author . Robert J. Motzer, MD, A medical oncologist and a chair in oncology at the Memorial Sloan Kettering Cancer Center, said at a press conference.
About 65,000 kidney cancer cases are diagnosed each year in the United States. Early treatment usually consists of surgical resection, but since there are few warning signs of the disease, approximately 50% of patients will have metastases at the time of initial diagnosis or after nephrectomy.
Sunitinib (Sutent, Pfizer), a multi-target tyrosine kinase inhibitor, has been a standard treatment for kidney cancer since it was approved by the FDA in 2006.
Several compounds are now similar to sunitinib. One of these is axitinib (Inlyta, Pfizer), a small molecule tyrosine kinase inhibitor approved for the second-line treatment of kidney cancer.
"Axitinib has an advantage over sunitinib in that it has less toxicity, particularly liver toxicity, so it combines better with other drugs," Motzer said.
Inhibitors of immune control points have also become a primary treatment option.
In the JAVELIN Renal 101 trial, Motzer and his colleagues compared the association of axitinib and avelumab (Bavencio; EMD Serono, Pfizer), a fully human monoclonal antibody targeting PD- L1, with sunitinib for the first-line treatment of advanced clear cell renal cells. carcinoma.
The analysis involved 886 patients with an ECOG performance index of 0 or 1 and no previous systemic treatment. All prognostic risk groups were included (21% favorable risk, 62% intermediate risk, 16% low risk, <1% not reported).
The researchers randomized 442 patients on IV avelumab at 10 mg / kg every two weeks, with 5 mg axitinib orally twice daily per 6-week cycle. The other 444 patients received 50 mg of sunitinib daily orally every 4 weeks without interruption.
The primary endpoints included PFS – assessed by independent central blind review – and OS in patients with PD-L1 positive tumors (n = 560), defined by 1% or greater expression on immune cells. . Secondary endpoints included PFS and OS regardless of PD-L1 expression, as well as objective response and safety.
The axitinib-avelumab combination appeared associated with longer median PFS in the subgroup of patients with PD-L1 positive disease (13.8 months vs. 7.2 months, HR = 0). , 61; P <0.001), as well as across the entire cohort, regardless of PD-L1 expression (13.8 months vs. 8.4 months, HR = 0.69; P = 0.0001).
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The researchers also reported higher objective response rates in patients assigned to the experimental combination in the two PD-L1 positive subgroups (55.2% vs. 25.5%, stratified OR = 3.73; P <0.0001) and the entire cohort (51.4% vs. 25.7%, stratified OR = 3.09; P <.0001).
Less than 16% of patients experienced events by the data submission deadline. The data relating to SG were therefore not mature.
The safety profiles of axitinib and avelumab appeared to match previous studies on each drug.
"Safety is of paramount importance when evaluating a new combination," Motzer said.
A similar percentage of patients treated with axitinib-avelumab and sunitinib monotherapy had treatment-related grade 3 or greater adverse events (71.2% vs. 71.5%).
The most common grade 3 / grade 4 toxicities were diarrhea (55% vs. 55%) and hypertension (24% vs. 15%). A higher percentage of patients treated with sunitinib had Grade 3 neutropenia (7 vs <1), anemia (5 vs <1) or thrombocytopenia (5 vs <1).
A higher percentage of patients assigned to the association stopped the study drug due to adverse events (22.8% vs. 13.4%). Less than 1% of patients in each treatment group died from treatment toxicity (0.7% for combination versus 0.2% for sunitinib).
"The results are catchy," Thomas Powles, MD, Oncologist consultant Barts Health NHS Trust in London, said in a press release.
"Response rates are twice the previous standards of care, and unprofessional survival is becoming a very impressive area for a randomized trial," added Powles, who did not participate in the study. 39; study. "This approach consists in immediately giving the combinations of the most active agents; therefore, there is uncertainty as to whether this will result in a survival signal as impressive as that seen with other combinations of immunotherapy. "- Mark Leiser
Reference:
Motzer RJ et al. Abstract LBA6_PR. Presented at: Congress of the European Society of Medical Oncology; October 19-23, 2018; Munich.
Disclosures: Pfizer sponsored the lawsuit, which is part of an alliance between Pfizer and Merck KGaA, based in Darmstadt, Germany. Motzer announces research funding or consulting / consulting positions with Bristol-Myers Squibb, Eisai, Exelixis, Genentech / Roche, GlaxoSmithKline, Incyte, Merck Sharpe & Dohme, Novartis and Pfizer.
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