No benefit observed after resection in early stage cancer

Post-operative radiotherapy does not appear to benefit non-small-cell lung cancer patients who have undeergone complete resection of the cancer but still have mediastinal nodal involvement, researchers suggested at the 2020 virtual meeting of the European Society for Medical Oncology (ESMO)

Over the course of 3 years, disease-free survival was achieved by 47.1% of patients who underwent the radiation treatment compared with 43.8% disease-free survival in patients who did not receive radiation therapy after their definitive surgery (P=0.16), reported Cécile Le Pechoux, MD, professor of medicine at the Institute Gustave Roussy, Paris.

At a press conference sponsored by ESMO, Le Pechoux said that translated to a median disease-free survival of 22.8 months among the 249 patients who were assigned to the control arm of the so-called PORT ART study compared with a median survival of 30.5 months in the 252 patients who were assigned to receive conformal radiation.

There was no statistically significant difference in overall survival, she reported. The overall survival among the patients who received radiation was 66.5% at 3 years, and was 68.5% in the patients who did not undergo radiation, she said.

“Based on these studies,” Le Pechoux said, “conformal post-operative radiotherapy cannot be recommended as a standard of care in all completely resected Stage IIIAN2 non-small-cell lung cancer. More toxicities were observed in the post-operative radiation arm, especially cardio-pulmonary toxicity – 11% in the post-operative radiation arm versus 5% in the control arm – that need to be further explored.”

In commenting on the study at the press conference, Rafal Dziadziuszko, MD, PhD, professor of oncology at the Medical University of Gdansk, Poland, said, “Radiotherapy to the mediastinum after surgery, after adjuvant chemotherapy shouldn’t be recommended as standard of care. This will change the practice of many institutions that adopted standard use of radiotherapy in these patients. We can safely say there is no net benefit from such treatment but there is also potential harm, which we see from this study, so any potential benefits in some patients are offset by the predominantly higher risk of cardiopulmonary toxicities.”

Le Pechoux said that whether to use post-operative radiation in the population study has been controversial. To answer that controversy, the Phase III trial enrolled patients who had been diagnosed with non-small-cell lung cancer that had been completely resected, but the patients were also found to have N2 involvement proven by histo-cytology, she said. The aim of the trial was to show at least a 12% improvement in disease-free survival for those receiving radiation at 3 years — but the study was far short of reaching that milestone.

The researchers were concerned about the toxicities observed in the trial, especially the excess toxicity that emerged among the patients who received radiotherapy.

At least one toxicity was reported in 81.3% of the patients in the control arm who just underwent surgery, but Le Pechoux reported that 92.1% of the patients who received radiation had at least one toxicity. Serious adverse events – Grade 3 or Grade 4 occurred in 15% of the control patients and in 23.7% of the patients who received radiation. The radiation dose in the study was 54 Gray delivered over 5.5 weeks.

The first event in the disease-free survival analysis was most often recurrence of disease in the mediastinum. Of the 152 events that occurred in the control arm, 46.1% were mediastinal recurrence in that group compared with 25% of the 144 patients with disease-free survival events in the radiation arm. Brain metastases occurred more often in the radiotherapy arm – 23.6% compared with 17.6% among the control arm patients. Death, as a first event. Occurred in 21 radiation patients and 8 control arm patients, the researchers reported.

“Possibly, however, for some patients post-operative radiotherapy might be useful because it does decrease the rate of mediastinal relapse by 50%,” Le Pechoux said. “This must be put into balance with the risk of over-added cardio-pulmonary toxicity. We need to do further analysis to determine if certain patients could benefit from it.”

Edward Susman, Contributing Writer, BreakingMED™

Le Pechoux disclosed relationships with Amgen, AstraZeneca, Lilly, Medscape, Roche and Nanobiotix.

Dziadziuszko disclosed relationships with Pfizer, Novartis, Roche, Clovis, Boehringer-Ingelheim and Tesaro.

 

Cat ID: 24

Topic ID: 78,24,728,791,730,24,192,65,925,482,159,492,696