Cetuximab (Erbitux) added no survival benefit to chemoradiation in stage III non–small cell lung cancer (NSCLC), according to results reported in a Plenary Session of the 2013 World Conference on Lung Cancer in Sydney, Australia.1
It was the second surprise result from the Radiation Therapy Oncology Group (RTOG) 0617 trial. Two years ago, investigators reported that contrary to expectation, a higher dose of radiation therapy (74 Gy) reduced, rather than increased, overall survival and local control compared to the standard 60 Gy. The findings reported in Sydney showed that the addition of cetuximab had no effect on survival in either arm and increased the number of grade 3 and higher adverse events.
Several possible reasons for the surprising results are under review, including cardiac toxicity, said Maria Werner-Wasik, MD, Director of Clinical Research in the Department of Radiation Oncology at Thomas Jefferson University, Philadelphia. Dr. Werner-Wasik discussed highlights of the Sydney meeting in a live webinar organized by the International Association for the Study of Lung Cancer (IASLC). The webinar also covered radiation oncology highlights from the 2014 ASCO Annual Meeting (see page 35). The recorded webinar is available on the IASLC website.2
Smart Dose Escalation
Despite the RTOG 0617 results, the study of dose escalation in stage III NSCLC is not over, said Dr. Werner-Wasik. Studies are now looking at other strategies to increase the total dose of radiation to the lung tumor without harming surrounding tissues.
“Smart dose escalation is in,” she said. One kind of smart dosing is isotoxic dose escalation, in which dose is personalized for each patient. In the UK’s Isotoxic Dose Escalation and Acceleration in Lung Cancer (IDEAL) trial, for example, doses are adjusted based on computed tomography (CT) scan monitoring of the heart, spinal cord, and brachial plexus.
Other ways to increase dose, such as hypofractionation (higher doses in fewer radiation sessions) or use of protons/charged particles, are also under study.
Recurrence After SBRT
Dr. Werner-Wasik also focused on several studies with stereotactic body radiation therapy (SBRT), a technique that precisely locates tumors in the body to avoid damage to surrounding tissue and delivers few (1–5) large radiation doses or fractions. RTOG 0915, for example, a randomized phase II trial, compared SBRT delivered with a single 34-Gy fraction to 48 Gy given with four fractions of 12 Gy each, in patients with inoperable stage I peripheral NSCLC.3
The results favored the more convenient one-dose regimen, showing no difference between the two arms in grade 3 and higher adverse events, the primary endpoint of the trial. There was also no difference in overall survival or local control at 1 year. Plans are underway for a phase III trial, once longer follow-up confirms the same local control in both groups.
One of the issues with stereotactic body radiotherapy is that it produces fibrosis, which can make it difficult to monitor for local recurrence. “Evaluation of recurrence after SBRT,” Dr. Werner-Wasik said, “remains an unresolved and vexing issue for all of us in clinical practice.”
An important study used CT scans to assess potential high-risk features associated with biopsy-confirmed recurrences, finding that the presence of three or more factors was highly sensitive and specific for recurrence.5 The most predictive single feature was enlarging opacity after 12 months.
Another concern with stereotactic body radiotherapy is that toxicity may limit its use for central tumors. But in a large multinational data set, patients treated with SBRT had the same overall survival and the same rate of grade 3 and higher adverse events, regardless of whether they had central or peripheral tumors.6 The conclusion, Dr. Werner-Wasik said, was that SBRT is safe for both central and peripheral tumors, although optimal SBRT dose for central tumors remains to be established. ■
Disclosure: Dr. Werner-Wasik reported no potential conflicts of interest.
References
1. Bradley J, Masters G, Hu C, et al: An intergroup randomized phase III comparison of standard-dose (60 gy) versus high-dose (74 gy) chemoradiotherapy (CRT) +/- cetuximab (cetux) for stage III non-small cell lung cancer (NSCLC): Results on cetux from RTOG 0617. World Conference on Lung Cancer. Abstract PL03.05. Presented October 29, 2013.
2. Updates on Radiation Oncology: WCLC 2013 AND ASCO 2014. July 18, 2014. Available at www.iaslc.org/webinars/updates-radiation-oncology-wclc-2013-and-asco-2014. Accessed August 25, 2014.
3. Videtic G, Hu C, Anurag Singh A, et al: Radiation Therapy Oncology Group (RTOG) protocol 0915: A randomized phase II study comparing 2 stereotactic body radiation therapy (SBRT) schedules for medically inoperable patients (pts) with stage I peripheral non-small cell lung cancer. World Conference on Lung Cancer. Abstract O10.02. Presented October 28, 2013.
4. Dosimetric predictors of esophageal toxicity after stereotactic body radiotherapy for central lung tumors. World Conference on Lung Cancer. Abstract MO17.09. Presented October 29, 2013.
5. Senthi S, Huang K, Palma D, et al: Blinded assessment of radiological changes after stereotactic ablative radiotherapy for early-stage lung cancer: Local recurrences versus fibrosis. World Conference on Lung Cancer. Abstract O10.05. Presented October 28, 2013.
6. Grills IS, Mangona VS, Hope A, et al: Recurrence, survival, and toxicity after stereotactic lung radiotherapy (SBRT) for central versus peripheral stage I non-small cell lung cancer (NSCLC): Results from an international collaborative research group. World Conference on Lung Cancer. Abstract MO17.05. Presented October 29, 2013.
