Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST). After activity was found in cell cultures, a Phase II study of refractory non-small-cell lung cancer found that “Sunitinib has provocative single-agent activity in previously treated pts with recurrent and advanced NSCLC, with the level of activity similar to currently approved agents.

A recent phase II study, resurrected interest in this drug. The Cancer and Leukemia Group B (CALGB) 30504 (ALLIANCE) study enrolled 144 patients with extensive stage (ES) SCLC, which is characterized by extrathoracic metastatic disease, malignant pleural effusion, contralateral supraclavicular adenopathy, or contralateral hilar adenopathy.

All patients were first treated with cisplatin or carboplatin and etoposide on days 1 through 3 every 3 weeks for four to six cycles. Patients achieving a complete response (CR) or a partial response (PR) then went on to receive prophylactic cranial irradiation (PCI), the standard of care in SCLC.

Patients who achieved a CR, a PR, or stable disease (SD) were randomly assigned in a double-blinded manner to maintenance sunitinib (a loading dose of 150 mg on day 1, then 37.5 mg daily) or placebo. Maintenance therapy was initiated anytime between week 3 and week 8 after day 1 of the last chemotherapy cycle.

The results show that PFS was significantly longer for patients receiving maintenance sunitinib: 3.7 months vs 2.1 months for those receiving placebo (P = .022). With a hazard ratio of 1.62 (placebo vs sunitinib), patients receiving maintenance sunitinib had a 62% lower risk for progression (95% confidence interval: 1.02 – 2.60).

Median OS was also longer for patients receiving maintenance sunitinib (9.0 months vs 6.9 months for placebo); however, OS did not achieve significance (P = 0.16); 1-year OS was 63% for patients receiving sunitinib and 44% for those receiving placebo.

However, this was for maintenance and not for treatment as in this case. There are no guidelines or phase III studies that support sunitininb for use in small cell lung cancer.

Natasha B. Leigh Sunitinib: The Next Advance in Small-Cell Lung Cancer? JCO April 13, 2015

Neal E. Ready 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) JCO March 2, 2015

Socinski MA et al. (2006). “Efficacy and safety of sunitinib in previously treated, advanced non-small cell lung cancer (NSCLC): preliminary results of a multicenter phase II trial”. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I 24 (18S (June 20 suppl)).