The Lung ART trial was designed to demonstrate whether there was any benefit to the routine use of modern mediastinal postoperative radiotherapy in patients with non–small cell lung cancer (NSCLC) following complete resection and (neo)adjuvant chemotherapy. No difference in disease-free survival was observed between patients who received postoperative radiotherapy and those who did not in this large randomized phase III trial. These results were reported at a Presidential Symposium during the ESMO Virtual Congress 2020 (Abstract LBA3_PR).
“This study provides a long-awaited answer for the oncology community,” said lead study author Cécile Le Pechoux, MD, a radiation oncologist at Institut Gustav Roussy, Paris. “Our study shows that postoperative radiotherapy cannot be recommended for all patients with stage II and III NSCLC with mediastinal nodal involvement. Possibly, however, for some patients, it might be useful, because it does decrease the rate of mediastinal relapse by 50%. This must be put in balance with the risk of over-added cardiopulmonary toxicity. We need to do further analysis to determine if certain patients, in particular, could benefit from postoperative radiotherapy,” she noted.
Cécile Le Pechoux, MD
“Adjuvant chemotherapy following complete resection has been the standard of care for patients with NSCLC. The addition of postoperative radiotherapy has been debated for many years in patients with mediastinal nodal involvement. The question has remained open, since the risk of locoregional recurrence [for these patients] is between 30% and 60%,” she said.
Study Details
Lung ART was designed as a phase III randomized trial in patients with NSCLC and mediastinal nodal involvement treated with surgery and (neo)adjuvant chemotherapy. Patients (n = 501) were randomly assigned 1:1 to receive conformal postoperative radiotherapy at 54 Gy for 5.5 weeks or no treatment after chemotherapy and surgery (control group). The primary endpoint was disease-free survival. Secondary endpoints were overall survival, patterns of relapse, local failure, and treatment-related toxicity. The investigators prespecified that a 12% improvement in disease-free survival was needed to show significance.
The difference in disease-free survival was not statistically significant. Median disease-free survival was 30.5 months for the postoperative radiotherapy arm and 22.8 months for the control arm. The 3-year disease-free survival was 47.1% in the postoperative radiotherapy arm vs 43.8% in the control arm. Slightly more first disease-free survival events were reported in the controls. Mediastinal relapse was significantly reduced with postoperative radiotherapy: 25% vs 46.1% in the control arm.
The rate of 3-year overall survival was 66.5% in the postoperative radiotherapy arm vs 68.5% in the control arm. There was no difference in overall survival between the two arms. Death as the first disease-free survival event was reported in 21 patients in the postoperative radiotherapy arm (14.6%) and 8 patients in the control arm (5.3%).
“These results are good in terms of outcome, since these are high-risk patients. More than two-thirds are [still] living at 3 years,” said Dr. Le Pechoux.
Safety was assessed in 422 patients. Almost one-quarter (23.7%) of patients in the postoperative radiotherapy arm experienced at least one grade 3 or 4 adverse event vs 15% of the control arm. The rate of at least one early toxicity was higher in the postoperative radiotherapy arm: 11.6% vs 7.7% for the control group. The rate of at least one late toxicity was also higher among patients in the postoperative radiotherapy arm: 14.6% vs 8.9% for the control arm.
"At the moment, conformal postoperative radiotherapy cannot be recommended as standard of care for all [patients with] completely resected stage III mediastinal node-positive NSCLC."— Cécile Le Pechoux, MD
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Commentary
“Lung ART is the first European randomized study evaluating modern postoperative radiotherapy after complete resection in patients selected having received (neo)adjuvant chemotherapy. Three-year disease-free survival and overall survival were higher than expected in both arms. Mediastinal relapse was reduced by half in the postoperative radiotherapy arm. There was more toxicity in the postoperative radiotherapy arm, especially cardiopulmonary toxicity. This needs to be further explored,” stated Dr. Le Pechoux.
“At the moment, conformal postoperative radiotherapy cannot be recommended as standard of care for all [patients with] completely resected stage III mediastinal node-positive NSCLC. Further analyses are planned to determine patterns of failure and predictive factors of efficacy and toxicity,” she said. “We don’t know yet which patients would benefit from postoperative radiotherapy. This is the reason why we do further studies. We collected a lot of data, and it may be that postoperative radiotherapy would be more toxic to patients with [a] tumor located closer to the heart or interior nodes. For the moment, based on stratification factors, we don’t have anything that will give us a clue. We will do more digging…. There is a lot to investigate.”
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
