No Difference Between Temsirolimus/Bevacizumab vs Interferon Alfa/Bevacizumab in First-Line Therapy for Metastatic Renal Cell Carcinoma
In the phase III INTORACT trial reported in the Journal of Clinical Oncology, Rini et al compared temsirolimus (Torisel)/bevacizumab (Avastin) vs interferon alfa/bevacizumab in first-line treatment of metastatic renal cell carcinoma. There were no significant differences between the two regimens in progression-free survival, overall survival, or objective response rate.
Study Details
In this open-label international trial, 791 patients with previously untreated predominantly clear cell metastatic renal cell carcinoma were randomly assigned to receive intravenous temsirolimus at 25 mg weekly (n = 400) or subcutaneous interferon alfa at 9 MIU thrice weekly (n = 391) along with intravenous bevacizumab at 10 mg/kg every 2 weeks. The primary endpoint was progression-free survival.
The temsirolimus/bevacizumab and interferon alfa/bevacizumab groups were well matched for age (median, 59 and 58 years), sex (72% and 69% male), race (82% and 85% white), Karnofsky performance status (70% and 74% ≥ 90), prior nephrectomy (85% and 86%), prior radiotherapy (11% and 9%), and Memorial Sloan-Kettering Cancer Center prognostic group (58% and 61% intermediate, 12% and 10% poor).
No Efficacy Differences
Median progression-free survival was 9.1 months in the temsirolimus/bevacizumab group and 9.3 months in the interferon alfa/bevacizumab group (hazard ratio [HR] = 1.1, P = .8). There were no significant differences between treatments in subgroup analysis according to prior nephrectomy, Memorial Sloan-Kettering Cancer Center prognostic group, age, sex, race, or geographic region. There were no significant differences between groups in overall survival (median, 25.8 vs 25.5 months, HR = 1.0, P = .6) or objective response rate (27.0% vs 27.4%).
Adverse Events
Adverse events led to discontinuation of treatment in 22% of the temsirolimus/bevacizumab group vs 19% of the interferon alfa/bevacizumab group, dose reduction in 30% vs 38% (most common reason, mucosal inflammation in 5% vs asthenia in 8%), and treatment delay in 70% and 62% (most common reason, proteinuria in 17% vs 14%).
Adverse events of any grade that were significantly more common (all P < .05) in the temsirolimus group were hypercholesterolemia (32% vs 10%), rash (32% vs 8%), mucosal inflammation (27% vs 10%), stomatitis (26% vs 10%), hyperglycemia (22% vs 5%), and peripheral edema (17% vs 8%); those significantly more common in the interferon alfa group were pyrexia (39% vs 21%), neutropenia (17% vs 5%), and myalgia (15% vs 5%).
Grade 3 or higher adverse events occurred in 80% of the temsirolimus/bevacizumab group vs 76% of the interferon alfa/bevacizumab group and serious adverse events occurred in 45% vs 38%. Grade 3 or higher adverse events that were significantly more common (all P < .05) in the temsirolimus/bevacizumab group were mucosal inflammation (8% vs < 1%), stomatitis (7% vs 2%), hypophosphatemia, hyperglycemia (6% vs 1%), and hypercholesterolemia (6% vs 1%); those significantly more common in the interferon alfa/bevacizumab group were neutropenia (8% vs 2%) and myalgia (3% vs 0%). Pneumonitis, mostly grade 1 or 2, occurred in 5% of the temsirolimus group.
Death due to treatment-related adverse events occurred in 1.0% of the temsirolimus/bevacizumab group and 1.8% of the interferon alfa/bevacizumab group.
Patient-Reported Outcomes
Patients in the temsirolimus/bevacizumab group had statistically significantly higher mean scores on the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI)-15 (P = .002)and FKSI-Disease Related Symptoms subscale (P < .001), but the differences did not meet predefined criteria for clinical significance. There were no differences between groups in global health outcomes assessed by the European Quality of Life-5 Dimensions score (EQ-5D) or the EQ-5D visual analog scale.
The investigators concluded: “[T]emsirolimus/bevacizumab was not superior to [interferon alfa]/bevacizumab as first-line therapy for patients with clear cell [metastatic renal cell carcinoma]. Safety data were consistent with known profiles of these agents when given as monotherapy. [Interferon alfa]/bevacizumab remains the only combination regimen with demonstrated benefit for first-line treatment of advanced [renal cell carcinoma].”
Brian I. Rini, MD, of the Cleveland Clinic Taussig Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
The study was sponsored by Wyeth Research, which is owned by Pfizer. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
