This is the first trial evaluating an antiangiogenic agent as maintenance therapy in advanced NSCLC.
—Mark A. Socinski, MD
Progression-free survival was significantly improved among patients with advanced non–small cell lung cancer (NSCLC) receiving sunitinib (Sutent) as switch maintenance compared to placebo, according to results of an Alliance phase III trial (Cancer and Leukemia Group B [CALGB] 3067). The effect of sunitinib as switch maintenance on progression-free survival was seen independent of histology, the trials lead investigator, Mark A. Socinski, MD, reported at the Plenary Session of the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. No effect was seen on overall survival. Dr. Socinski is Director, Lung Cancer Section, Division of Hematology Oncology, at the University of Pittsburgh Cancer Institute.
Sunitinib, an oral tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor and other kinases, “has shown single-agent activity in advanced NSCLC,” Dr. Socinski noted, and an acceptable toxicity profile. “This is the first trial evaluating an antiangiogenic agent as maintenance therapy in advanced NSCLC,” he added.
First-Line Platinum-Based Doublet
In CALGB 3067, “similar to all the maintenance trials, patients received four cycles of a first-line platinum-based doublet,” Dr. Socinski said. Patients with nonprogressive disease were randomly assigned to sunitinib at 37.5 mg daily (106 patients) or placebo (104 patients) until disease progression. Bevacizumab (Avastin) “was allowed during first-line treatment but the treating physician had to be willing to discontinue it after the fourth cycle,” Dr. Socinski noted.
Stratification factors included stage of disease (IIIB vs IV), performance status (0 and 1 vs 2), prior use of bevacizumab (yes or no), and gender. Fewer than half the patients were female in the sunitinib group (46.2%) and the placebo group (42.3%). The average age was 65 in the sunitinib group and 67 in the placebo group. Patients could have no cavitary lesions or symptomatic or untreated brain metastases.
“The dominant histology was adenocarcinoma,” Dr. Socinski reported. “Squamous cell carcinoma was second.” Most patients were past smokers, and about 25% were current smokers.
Primary Endpoint Met
The study “met its primary endpoint, showing a significant improvement in [progression-free survival] for sunitinib as switch maintenance in advanced NSCLC,” Dr. Socinski observed. Median progression-free survival was 4.3 months with sunitinib vs 2.6 months with placebo (hazard ratio [HR] = 0.61, P = .0005). The secondary endpoint of overall survival was not met, being 11.7 months in both groups.
“The toxicity was different, as one would expect,” Dr. Socinski noted, consistent with known sunitinib side effects and with no new toxicity signals identified. There were increases in all grades of neutropenia, thrombocytopenia, and anemia, which occurred in 1% of placebo recipients but 12%, 18%, and 14%, respectively, of sunitinib recipients. Most of the differences in nonhematologic toxicities occurred in all grades, but patients receiving sunitinib were more likely to have grade 3/4 mucositis, rash, hypertension, and fatigue.
Results in Context
In addition to achieving its goal of increasing progression-free survival, “the overall response rate was actually numerically better for sunitinib than placebo, 11.3% vs 5%, noted Plenary Session discussant Vassiliki A. Papadimitrakopoulou, MD, Jay and Lori Eisenberg Endowed Professor of Medicine at The University of Texas MD Anderson Cancer Center in Houston.
“To put this in context,” Dr. Papadimitrakopoulou presented data from other maintenance trials. Those data showed median a progression-free survival of 3.9 and 4 months from maintenance trials with pemetrexed (Alimta), comparable to the 4.3 months in the sunitinib trial results presented by Dr. Socinski. “This is a little better than we have seen with erlotinib,” she added, with median progression-free survival of 2.9 month, and “inferior to what we have seen with the combination of therapy with bevacizumab and erlotinib,” with median progression-free survival of 4.8 months.
While the effect of sunitinib was seen independent of histology, Dr. Papadimitrakopoulou cautioned that this was “at the expense of toxicity, with myelosuppression, mucositis, hypertension, fatigue, and rash. There were three deaths on study and no improvement in overall survival.”
Dr. Papadimitrakopoulou added, “bevacizumab remains a standard practice option for patients with nonsquamous NSCLC,” but noted that predictive biomarkers and selection strategies are still unavailable for both bevacizumab and sunitinib. ■
Disclosure: Dr. Socinski’s institution receives research funding from Pfizer. Dr. Papadimitrakopoulou is a consultant for Merck, Biothera, Genentech, ACEA Biosciences, Clovis, Janssen, Gensignia Life Sciences, AstraZeneca, and Lilly, and has received research support from Merck, Medimmune, BMS, AstraZeneca, Janssen, Clovis, Novartis, Astellas, and Celgene.
1. Socinski MA, Wang X, Baggstrom M, et al: Sunitinib (S) switch maintenance in advanced non-small cell lung cancer (NSCLC): An Alliance (CALGB 30607), randomized, placebo-controlled phase III trial. Chicago Multidisciplinary Symposium in Thoracic Oncology. Abstract 1. Presented October 31, 2014.
2. Papadimitrakopoulou V: What is new in NSCLC in 2014. Chicago Multidisciplinary Symposium in Thoracic Oncology. Presented October 31, 2014.