Postoperative Radiotherapy Not Associated With Improved DFS in NSCLC

In patients with completely resected non–small cell lung cancer with mediastinal N2 involvement, postoperative radiotherapy was not associated with an increase in disease-free survival.

Treatment with postoperative radiotherapy (PORT) was not associated with a better disease-free survival (DFS) than those who did not receive PORT in patients with completely resected non–small cell lung cancer with proven mediastinal N2 involvement, according to findings from the LUNG ART phase 3 trial (NCT00410683) published in The Lancet Oncology.

The 3-year DFS rate in the PORT group was 47% (95% CI, 40%-54%) compared with 44% (95% CI, 37%-51%) in the group that did not receive PORT. The median DFS qA 30.5 months (95% CI, 24-49) vs 22.8 months (95% CI, 17-37) in each group, respectively (HR, 0.86; 95% CI, 0.68-1.08; P = .18).

A total of 501 patients were enrolled ON the study after having completed surgery or adjuvant chemotherapy, 252 of whom were randomized to the PORT group and 249 in the control group. Patients had a median age of 61 years, and 6 patients had a performance status of 2 across both arms. Additionally, 46 patients were never smokers, 398 were former smokers, and 54 were current smokers.

Patients had a median interval of 4.2 months from surgery to random assignment. Furthermore, the median time from adjuvant chemotherapy to PORT was 36 days, translating to a median interval of 19 days from random assignment to the PORT. As investigators wanted to evaluate locoregional treatment via the International Association for the Study of Lunch Cancer, 139 patients had R0 resection, 203 had uncertain resection, and 149 had R1 resection.

In total, 480 patients received preoperative or postoperative chemotherapy or both, and 67 were treated with preoperative chemotherapy alone. Eleven patients in the PORT group did not receive radiotherapy, 201 had 3D conformal radiotherapy, and 25 had intensity modulated radiotherapy. Additionally, 230 patients were treated at a prescribed dose of 54 Gy.. The median heart and lung dose was 13 Gy, and investigators noted a 23% median percentage of the normal lung receiving at least 20 Gy.

The median follow-up was 4.8 years at the data analysis cutoff, and 18 patients were lost to follow-up. Investigators found that 296 patients experienced a recurrence or had died, including 144 in the PORT group and 152 in the control group. As a first event, 267 patients relapsed, 296 experienced DFS events, 106 experienced mediastinal relapse, 61 had brain failure, and 142 had extracranial metastatic failure. In addition, 29 patients had death as a first event.

A total of 201 patients died, including 99 in the PORT cohort and 102 in the control cohort. Most deaths were attributed to disease recurrence, including 87 in the control group and 68 in the PORT group. Additionally, 18 patients died from cardiopulmonary disease, 6 died from second primary cancer, 3 died from causes related to chemotherapy toxicity, and 19 died from pulmonary infection, vascular, or other causes.

The 3-year overall survival rate in the control group was 69% (95% CI, 61%-75%) and 67% (95% CI, 59%-73%) in the PORT group. Findings from an early analysis indicated that similar occurrences of death took place across groups (adjusted HR, 0.97; 95% CI, 0.73-1.28).

Early adverse effects (AEs) were observed in 398 patients, most of which were grade 1 or 2. Grade 3 or 4 early AEs were seen in 28 patients in the PORT group and 19 in the control group. Late toxicities were seen in 341 patients, which were also mostly grade 1 and 2. Additionally, 26 patients in the PORT group and 12 in the control group had late grade 3/4 cardiopulmonary toxicities. The most common grade 3/4 AEs were pneumonitis in 13 patients in the PORT group and 1 in the control group, lymphopenia in 9 patients from the PORT group and 0 in the control group, and fatigue including 6 in the PORT group and 1 in the control group.

Reference

Le Pechoux C, Pourel N, Barlesi F, et al. Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022;23(1):104-114. doi:10.1016/S1470-2045(21)00606-9