Cetuximab combined with chemoradiotherapy increases lung cancer survival while inducing side effects comparable to chemotherapy alone, offering promising phase II results that clinicians hope will roll over to an ongoing phase III trial.
The Radiation Therapy Oncology Group (RTOG) has conducted several trials aimed at optimizing treatment regimens for lung cancer, which is the leading cause of cancer deaths in the U.S., killing an estimated 157,300 people annually, primarily from non-small cell lung cancer (NSCLC). RTOG trials have examined the effectiveness and side effects of radiation therapy combined with chemotherapy.
In the present study, published June 10 in the Journal of Clinical Oncology, 93 patients with unresectable NSCLC underwent chemoradiotherapy plus cetuximab. The antibody is a molecularly targeted therapy that binds to the epidermal growth factor receptor (EGFR) to inhibit tumor growth and increase chemoradiosensitivity. Results were available for 87 participants.
Eighty-one patients successfully completed the cetuximab protocol, while 68 patients completed both the entire cetuximab and chemoradiotherapy regimens. Median survival was 22.7 months and two-year overall survival was 49.3 percent. These represented the strongest results of any previous RTOG trial to date, according to George R. Blumenschein Jr., MD, from the University of Texas MD Anderson Cancer Center in Houston, and colleagues.
Fifty-nine patients experienced grade three or higher adverse events, including six deaths that were potentially attributable to treatment. The authors noted that compared with standard chemoradiotherapy, the addition of cetuximab did not increase toxicity.
“Results from this trial demonstrate that cetuximab in combination with chemoradiation is well tolerated by patients with inoperable Stage III NSCLC,” Blumenschein stated. “The rate of severe side effects experienced by the study participants was commensurate with what has been widely reported for patients treated with the same chemoradiotherapy regimen alone.”
“This study was an important step in the pursuit to find the optimal regimen for the treatment of advanced NSCLC,” added co-researcher Walter J. Curran, MD, from Thomas Jefferson University Hospital in Philadelphia. “The improved survival rates seen with the addition of cetuximab to chemoradiotherapy in this phase II study are very promising and confirm the importance of further evaluation in a phase III setting.”
The phase III RTOG trial, which will likewise be a multi-institution study, has enrolled 90 percent of the planned 500 study participants to further evaluate the efficacy and safety of cetuximab with radiochemotherapy, according to the American College of Radiology-administered RTOG.