Maintenance Sunitinib Improves Progression-Free Survival in Phase II Trial in Untreated Extensive-Stage Small Cell Lung Cancer
In the randomized phase II Cancer and Leukemia Group B (CALGB) 30504/Alliance trial reported in the Journal of Clinical Oncology, Ready et al found that sunitinib (Sutent) vs placebo maintenance following chemotherapy improved progression-free survival in patients with previously untreated extensive-stage small cell lung cancer.
Study Details
In the study, 138 patients received chemotherapy consisting of cisplatin 80 mg/m2 or carboplatin AUC 5 on day 1 plus etoposide 100 mg/m2 per day on days 1 to 3 every 21 days for four to six cycles. Patients without disease progression were randomly assigned to receive maintenance sunitinib 37.5 mg or placebo daily until disease progression. Crossover after disease progression was allowed. The primary endpoint was progression-free survival from randomization for maintenance.
Improved Progression-Free Survival
Of 95 patients without disease progression who were randomly assigned to sunitinib vs placebo, 85 received maintenance sunitinib (n = 44) or placebo (n = 41). Prophylactic cranial irradiation had been received by 36% of sunitinib patients and 44% of placebo patients. Median progression-free survival was 3.7 months with sunitinib vs 2.1 months for placebo (hazard ratio [HR] = 1.62, P = .02, for placebo vs sunitinib). Median overall survival from randomization was 9.0 vs 6.9 months (HR = 1.28, P = .16, for placebo vs sunitinib). Complete response was observed during maintenance in three patients in the sunitinib group.
A total of 18 placebo patients crossed over to sunitinib after disease progression. Of the 13 who were evaluable for response, 10 (77%) had stable disease for 6 to 27 weeks. An unplanned analysis showed that among these 13 patients, median progression-free survival was 2.6 months during placebo treatment and 4.9 months after crossover to sunitinib.
Adverse Events
The most common grade 3 adverse events were fatigue (19%), neutropenia (14%), leukopenia (7%), and thrombocytopenia (7%) in sunitinib patients and fatigue (10%) in placebo patients. Grade 4 adverse events consisted of gastrointestinal hemorrhage in one patient and pancreatitis, hypocalcemia, and elevated lipase in one patient in the sunitinib group and thrombocytopenia in one patient and hypernatremia in one patient in the placebo group.
The investigators concluded: “Maintenance sunitinib was safe and improved [progression-free survival] in extensive-stage [small cell lung cancer].”
They noted: “A randomized phase II trial studying maintenance sunitinib with [overall survival] as the primary endpoint would be an appropriate next step, especially if the trial design incorporated a candidate sunitinib benefit predictive biomarker for retrospective validation. These results support the future study of multitargeted VEGFR inhibitors in [small cell lung cancer], especially as candidate predictive biomarkers are identified and in combination with new therapeutic strategies.”
Neal E. Ready, PhD, MD, of Duke University Medical Center, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by grants from the National Cancer Institute. 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®.
