Sunitinib, an oral multitargeted tyrosine kinase inhibitor with antiangiogenic activity, may help improve progression-free survival (PFS) in patients with small-cell lung cancer (SCLC) and should be studied in a phase III trial, according to Natasha Leighl, MD, of Princess Margaret Cancer Center at the University of Toronto in Toronto, Canada.
Dr. Leighl has been studying the available agents for treating SCLC patients and recently published an editorial published in the Journal of Clinical Oncology, writing that a phase II study has demonstrated a clear signal of benefit with sunitinib and further trials are warranted to determine whether this agent could extend patient survival.1
“SCLC remains an important disease in which we have not made major progress. The current study of sunitinib maintenance is interesting and may merit further study. There are many potential targets that we need to consider, and we should also reconsider whether SCLC should be treated as a single entity or whether there are molecular subgroups of the disease, as we have learned in non-small cell lung cancer. Drug development in SCLC may need to consider both paradigms and better treatments are urgently needed,” Dr. Leighl told Cancer Therapy Advisor.
The current 5-year survival rate for SCLC is estimated to be 6% and it is less than 3% in patients with extensive disease.
Approximately 100 drugs are in development for treating lung cancer but only a small fraction are being studied in patients with SCLC. Some of the agents now under investigation include immune checkpoint inhibitors, aurora kinase inhibitors, temozolomide maintenance, and VEGF/VEGFR inhibitors and cancer vaccines.
In a study published with Dr. Leighl’s editorial, researchers conducted a phase II trial that included 85 SCLC patients and found that that maintenance sunitinib was safe and improved PFS in extensive-stage SCLC.2 In this trial, 44 patients were treated with sunitinib and 41 were given placebo.
The researchers found that the median PFS survival was 2.1 months for placebo and 3.7 months for sunitinib (HR: 1.62). The median overall survival (OS) was 6.9 months for placebo compared to 9.0 months for sunitinib (HR: 1.28).
The researchers also reported that 3 patients who received sunitinib achieved a complete response and 13 patients evaluable after cross-over (77%) had stable disease on sunitinib (6 to 27 weeks).
In this study, the most common grade 3 adverse events (AEs) included fatigue (19%), decreased neutrophils (14%), decreased leukocytes (7%), and decreased platelets (7%) for patients treated with sunitinib.
RELATED: Maintenance Sunitinib Safe, Effective for Extensive-Stage Small-Cell Lung Cancer
The grade 4 adverse events reported in the sunitinib arm of the study were GI hemorrhage in one patient and pancreatitis, hypocalcemia, and elevated lipase in another patient.
“The biggest hurdle remains the aggressive course of the disease and our lack of understanding of the major drivers of SCLC, treatment resistance, and how to overcome these. There is also a lack of enthusiasm and investment from industry. More research funding would lead to greater understanding of the biology of SCLC, more trials, and hopefully more breakthroughs in therapy,” said Dr. Leighl.
She noted that VEGF and VEGF receptor inhibitor trials in patients with lung cancer have been disappointing. The standard systemic treatment of SCLC has not changed in decades even though new agents have been developed as alternatives.
Daniel Morgensztern, MD, of the Department of Medical Oncology at Washington University School of Medicine in St. Louis, MO, said the best hope for a substantial improvement in outcomes in patients with SCLC is the transition from empirical therapy to rationally designed studies with predictive biomarkers.
“We need better treatments to make some significant advances in SCLC. We need to have some new drugs. Sunitinib is just an old drug in a new role,” Dr. Morgensztern said in an interview with Cancer Therapy Advisor. “We have a long a way go. This is hardly a reason to celebrate. We have made a small step with sunitinib, but we need to make a big step.”
- Leighl NB. Sunitinib: the next advance in small-cell lung cancer? J Clin Oncol. April 13, 2015. [Epub ahead of print] pii: JCO.2014.60.1815.
- Ready NE, Pang HH, Gu L, 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. March 2, 2015. [Epub ahead of print] pii: JCO.2014.57.3105.