Lung ART Rules Out Postoperative Radiation For Completely Resected Stage IIIA N2 NSCLC

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Mediastinal postoperative radiotherapy (PORT) does not significantly improve disease-free survival (DFS) for stage III non-small-cell lung cancer (NSCLC) patients with proven N2 involvement, indicates research reported at the ESMO Virtual Congress 2020. 

Lung ART investigator Cécile Le Péchoux, from Institut Gustave Roussy in Villejuif, France, told delegates that the results mean “conformal PORT cannot be recommended as standard of care in all completely resected stage IIIA N2 NSCLC patients.” 

The phase III trial’s PORT and control treatment patient groups were “well balanced” in terms of sex, age, smoking status and histology, with most (96%) having received (neo)adjuvant chemotherapy, the presenter said. 

Similarly, around 40% of both groups had clinically unforeseen N2 status, with pathological (p) or post-neoadjuvant chemotherapy pathological staging indicating that 45% of patients had a single N2 station involved and 52% had two or more. The majority (78–81%) of patients underwent lobectomy and had confirmed pN2 disease at surgery, and 96% of the PORT arm completed their planned 54 Gy of radiation. 

However, the primary endpoint of DFS did not significantly differ between the 252 patients who were randomly assigned to receive conformal PORT and the 249 controls not given radiation, at a median 30.5 versus 22.8 months and a hazard ratio (HR) of 0.85. Three-year DFS was achieved by a comparable 47.1% and 43.8% of the groups, respectively. 

Further analysis revealed that PORT patients were less likely to experience mediastinal relapse as a first DFS event than controls (25.0 vs 46.1%) but were more likely to die as a first event (14.6 vs 5.3%). 

Overall survival (OS) was also similar between the PORT and control arms, with median 3-year rates of 66.5% and 68.5%, respectively. 

Although the mortality rates were comparable in the PORT and control groups (39.6 vs 41.5%), the causes of death differed; PORT was associated with higher rates of death from cardiopulmonary causes (16.2 vs 2.0%) and radiotherapy or chemotherapy toxicity (3.0 vs 0.0%), and a lower rate of death from disease progression or recurrence (69.4 vs 86.1%). 

Safety analysis indicated that, as expected, PORT patients were more likely to experience grade 3–4 early toxicity than controls (11.6 vs 7.7%) and at least one late toxicity at this severity (14.6 vs 8.9%), Cécile Le Péchoux said. 

PORT was also associated with an increased rate of late cardiopulmonary toxicity at grade 3–4 (10.8 vs 4.9%) or a second primary tumour (11.1 vs 7.2%), including second lung cancers (39.3 vs 22.2%). 

“These issues clearly need further analysis” and this is now planned, especially for the cardiopulmonary toxicity, the presenter commented. 

Discussing the Lung ART results at the session, Rafal Dziadziuszko, from the Medical University of Gdańsk in Poland, agreed that PORT cannot be recommended after completely resected NSCLC with mediastinal lymph node involvement, but remarked that patients with incomplete resection “should be treated with adjuvant radiotherapy as the local relapse rate is even higher in these patients.” 

He also stressed that the OS outcomes of both arms of the study were “impressive” and noted that “further improvements are expected from better systemic therapies”, such as adjuvant use of immune checkpoint inhibitors. 

Rafal Dziadziuszko concluded that the high risk of mediastinal relapse without PORT in this patient population “warrants careful follow-up with CT […], PET–CT and [endobronchial ultrasound] to allow for curative treatment with isolated nodal relapses”. 

Reference 

Le Péchoux C, Pourel N, Barlesi F, et al. An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement. Primary end-point analysis of LungART (IFCT-0503, UK NCRI, SAKK) NCT00410683. Ann Oncol 2020; 31 (Suppl 4): S1142–S1215. DOI:10.1016/annonc/annonc325