CHICAGO—Standard-dose radiation therapy (RT) is superior to high-dose RT in terms of overall survival (OS) and local-regional control in patients undergoing chemotherapy for locally advanced stage III non-small cell lung cancer (NSCLC), results of a study reported at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.
“This is a critical study in the field of radiation oncology,” said ASCO President Sandra M. Swain, MD, FACP. “After a decade of research, we can finally close the chapter on the high-dose versus standard-dose therapy debate in lung cancer therapy, using evidence-based data to improve care for our patients.”
The phase 3 Intergroup trial randomly assigned 464 patients to treatment with standard- or high-dose RT with concurrent weekly paclitaxel 45 mg/m2 and carboplatin AUC (area under the curve) 2 and cetuximab 400 mg/m2 loading dose on day 1 followed by weekly doses of 250 mg/m2 or no additional therapy.
Results showed the standard 60 Gy dose was safer and more effective than 74 Gy; patients on the high-dose arm had a 56% greater risk of death and a 37% increased risk of developing local failure. The high-dose arm was closed in June 2011 after an interim analysis showed it was not superior to the standard-dose arm. Use of the higher dose was based on results of phase 1 and 2 trials that suggested better outcomes.
“The biological reasons for failure of the high dose with respect to overall survival and local-regional control are not readily apparent,” said Jeffrey D. Bradley, MD, a professor of radiation oncology at the Washington University School of Medicine in St. Louis, MO. “Possible explanations are unreported toxicities, increased heart dose, extended therapy duration, grade 5 events, or likely a combination of these factors,” he added, The difference between arms in OS was also not accounted for by protocol deviations.
A total of 419 patients were evaluable for analysis. Median follow-up was 17.2 months. Median OS for patients in the standard-dose arm was 28.7 months compared with 19.5 months for the high-dose arm; estimated 18-month OS rates were 66.9% and 53.9%, respectively (hazard ratio [HR], 1.56; 95% CI: 1.19-2.06; P=0.0007). The 18-month progression-free survival rate was 36.6% versus 26.3% (HR, 1.3; 95% CI: 1.04-1.63; P=0.0116).
At 18 months, local recurrence rates were 34.3% in the high-dose arm versus 25.1% in the standard-dose arm (HR, 1.37; 95% CI: 0.99–1.89; P=0.0319); distant failure rates were 47.8% versus 42.4%, respectively.
The only significant difference in side effects was a slightly higher rate of esophagitis in the high-dose arm, 21% (7% in the standard-dose arm). Ten treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm.
The investigators noted that the effect of cetuximab awaits further follow-up.
This research was supported by the National Cancer Institute and Eli Lilly and Company.