COMMENTARY

An Important Negative Study for Post-op RT in Lung Cancer

Mark G. Kris, MD

Disclosures

October 08, 2020

This transcript has been edited for clarity.

Hello. This is Mark Kris from Memorial Sloan Kettering Cancer Center, speaking today about a presentation at the recent virtual meeting of the European Society for Medical Oncology (ESMO).

A clinical trial looking at the role of postoperative radiotherapy (PORT), the so-called Lung ART, was presented by European investigators. Approximately 500 patients were randomized to receive PORT (conformal type) or no radiotherapy after people had a complete resection from stage IIIA lung cancer and also received pre- or postoperative chemotherapy.

For the primary endpoint of the study, which was 3-year disease-free survival, there was only a 4% improvement with PORT. That was less than the amount of benefit that would be needed to declare this a positive trial. They were seeking 12%.

But then, of course, things get a little bit more complicated.

The median disease-free survival was improved by 9 months, from 22 months to 31 months, favoring PORT. Also, the degree of relapse in the mediastinum was decreased by more than 20%, from 46% down to 25%. Although PORT did not substantially improve overall survival, it did have some benefits in terms of improving the median [disease-free survival] and improving control in the chest.

They additionally found no difference in the amount of metastatic recurrences. That's what you would expect by giving a local therapy.

When they looked at overall deaths from the study, there were more deaths in the PORT arm from cardiopulmonary complications.

How does this change care? First, the amount of benefit from PORT is not huge. We can argue exactly how much it is, but it's not huge. That's exactly what this study showed. Second, there is a clear benefit in terms of local control but no benefit in terms of metastatic control.

The devil, of course, will be in the details. There may have been some patient groups within the patients studied that had more benefit, but that was not reported in this particular presentation. There will be more information as the trial is presented again and also published.

So the truth is that it doesn't change therapy at all.

The current ASCO guidelines on the use of PORT say, "Adjuvant radiotherapy is not recommended for routine use. A postoperative multimodality evaluation, including a consultation with a radiation oncologist, is recommended to assess the benefits and risks of adjuvant radiotherapy for each patient with N2 disease."

I think that remains the standard of care. It's important to have a radiation oncologist involved in these multimodality decisions to see what role, if any, there is for radiation. Clearly, there is benefit for some but not all. Plus, there is additional toxicity associated with it, which has to be offset by the benefit.

The other point is that patients with N2 disease still have a very difficult clinical course. Again, the disease-free survival for the PORT arm (the better arm) was only about 3 years — 33 months. We can do better. We need more research to find ways to benefit these patients and to improve the cure rate.

When you look at where they recur, the big area of recurrence is systemic. We need better systemic therapies.

Also, there is a dramatic improvement in disease-free survival when patients with EGFR-mutant disease receive adjuvant osimertinib. That is one step forward.

We now have more information about how to use PORT and whether or not PORT is a potential treatment for each and every patient with resected stage IIIA lung cancer.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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