Maintenance Sunitinib for Extensive-Stage Lung Cancer

Summary and Comment |
June 11, 2015

Maintenance Sunitinib for Extensive-Stage Lung Cancer

  1. Anne S. Tsao, MD

Progression-free survival was significantly longer with this tyrosine kinase inhibitor than with placebo.

  1. Anne S. Tsao, MD

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.

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.

Editor Disclosures at Time of Publication

  • Disclosures for Anne S. Tsao, MD at time of publication Consultant / Advisory board Genetech; Roche; Medimmune; Novartis; Astellas; Boehringer-Ingelheim; Eli Lilly Speaker’s bureau Genetech; Roche; Medimmune; Novartis; Astellas; Boehringer-Ingelheim; Eli Lilly Grant / Research support Department of Defense; SWOG Leadership positions in professional societies American Medical Association (Member); American Association of Cancer Research (Member); American Society of Clinical Oncology (Member); AACR-Women in Cancer Research (Member); International Mesothelioma Interest Group (Member); SWOG (Member); International Association for the Study of Lung Cancer (Communications Committee Chair); American Radium Society (Chair); RTOG (Member)

Citation(s):

Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
CAPTCHA
This question is for testing whether you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.