Loading...
Patients with small-cell lung cancer (SCLC) who receive chemotherapy usually experience relapse within 6 months and are often refractory to subsequent chemotherapy.
To test the efficacy of maintenance therapy with the small-molecule tyrosine kinase inhibitor sunitinib in this setting, investigators conducted a randomized, double-blind, placebo-controlled phase II trial (CALGB 30504) involving patients with extensive-stage SCLC. A total of 85 patients received maintenance sunitinib (37.5 mg daily) or placebo after four to six cycles of platinum-etoposide until disease progression. Placebo patients could cross over to sunitinib after progression.
Median progression-free survival (PFS) was significantly longer with maintenance sunitinib versus placebo (3.7 vs. 2.1 months; P=0.02); median overall survival was nonsignificantly longer with sunitinib (9.0 and 6.9 months). Three sunitinib recipients achieved a complete response. Of 13 placebo recipients who crossed over to sunitinib, 10 (77%) had disease stabilization. The main grade 3 adverse effects of sunitinib included fatigue (19% of recipients), neutropenia (14%), leukopenia (7%), and thrombocytopenia (7%). One sunitinib patient experienced a grade 4 gastrointestinal hemorrhage, and another experienced grade 4 pancreatitis, hypocalcemia, and elevated lipase. Of the 43 sunitinib recipients, 21 (49%) required dose modification.
Ready NE et al. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study — CALGB 30504 (Alliance). J Clin Oncol 2015 May 20; 33:1660. (http://dx.doi.org/10.1200/JCO.2014.57.3105)
Comment
This trial provides evidence that the angiogenic pathway in SCLC is a viable target for therapy. However, the toxicity associated with sunitinib was high, with nearly half of the recipients requiring dose modification. This trial began as a phase IB study, in which concurrent dose-escalation sunitinib was combined with chemotherapy. However, two of six patients died from fatal neutropenic sepsis, and the trial was redesigned into a phase II maintenance trial. Other anti-angiogenic agents with less toxicity may be better options. A randomized trial of nintedanib combined with front-line chemotherapy is currently under development by the Southwest Oncology Group.