Multimodality Treatment Approach Necessary in Stage III NSCLC

David P. Mason, MD

Immunotherapy has reinvigorated the once stagnant space of unresectable stage III lung cancer, but for eligible patients, surgery remains a core aspect of care in this setting, said David P. Mason, MD.

“I don't think surgery will ever go away,” added Mason, chief of thoracic surgery and lung transplantation, Baylor Scott & White Healthcare System. “Patients with stage III lung cancer who weren't being considered for surgery before, because it didn't seem like there was a significant additive benefit to justify the increased morbidity, may, [in fact], benefit from it and have better outcomes.”

In terms of patients with unresectable disease, the use of the checkpoint inhibitor durvalumab (Imfinzi) following concurrent chemoradiotherapy is now widely recognized as the preferred standard of care. The movement away from standard CCRT was based on data from the pivotal phase III PACIFIC trial, in which the addition of durvalumab to chemoradiation nearly tripled median progression-free survival and reduced the risk of progression or death by 49% compared with placebo.

“Immunotherapy as an adjunct to all of those modalities excites all of us,” said Mason. “It’s going to open up even more treatment [options] for patients.” However, he cautioned that the robust improvement in survival should not keep physicians from investigating additional approaches with the potential to prolong survival even further.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Non—Small Cell Lung Cancer, Mason, who is also the chief of lung transplantation, head of the Department of Thoracic Surgery, Baylor University Medical Center, discussed the available treatment approaches for patients with locally advanced non–small cell lung cancer (NSCLC).

OncLive: How far has stage III lung cancer treatment come?

Mason: Over the last few decades, not much has changed in the treatment of stage III lung cancer from both a surgical and medical perspective. However, over the last few years, we've seen a lot of progress made in stage III lung cancer. There are several therapies on the horizon that have the opportunity to change things for the better.

What is the standard approach now?

There are really two treatment modalities. One is chemotherapy and radiation, and the other is chemoradiation with surgery. It's hard to compare those two therapies because the patients who are selected for each approach often have different overall medical cross-sections. Typically, the patients who are selected for surgery are more fit; they may have more localized disease and are potentially more motivated to have surgery. There have been few randomized trials comparing the two treatments, and there is not a huge difference in the overall outcomes. However, in selected patients, there does seem to be some survival advantage for those who undergo surgery.

How do you determine if patients are eligible for surgery?

Often, the surgeon doesn't have the opportunity to meet certain patients because medical oncologists or radiation oncologists have a particular bias. Those patients may never be referred for surgery at all. Probably one-third to half of all patients with lung cancer need multimodality treatment. Patients who are in between the group of early-stage patients who typically proceed to surgery, stage II patients who receive adjuvant therapy, and stage IV patients, might potentially benefit from surgical therapy. In terms of the discussion I have with patients, I like to get a sense of their overall fitness and motivation to go through a challenging therapy on top of chemotherapy and radiation, which, in and of themselves, can be challenging.

What are some of the drawbacks with chemoradiation?

There are all of the secondary adverse events (AEs) of chemotherapy, which include nausea, vomiting, drop in blood counts, susceptibility to infection, admission to the hospitals, etc. With radiation, patients may experience esophagitis, discomfort, and lung injury; those are all downsides of chemoradiation. If you add surgery on top of that, it can be a particularly challenging regimen for patients.

What has the impact of immunotherapy been in the space for patients with unresectable disease?

We're still learning that. All of us realize that there is opportunity to improve overall outcomes. Even with the most aggressive therapies that we have, including surgery, higher-dose radiation, and new chemotherapy agents, survival is still disappointing. We would like to see better.

What would you like to see accomplished in the next 5 years in this space?

As a surgeon, I have a strong bias towards the value of surgery. There's probably an expanding role for surgery in patients with oligometastatic disease.

As chair of the meeting, could you speak to the value of holding these State of the Science Summits™?

This forum provides a space to ask questions. It’s an excellent way to build relationships. Stage III lung cancer holds the most opportunity and necessity for multidisciplinary interactions. A multimodality treatment approach is critical in this setting in order to determine who to treat and in which fashion. The ability to meet and interact with other oncologists and gain an understanding of what's important to them, their priorities, is very important.

Antonia SJ, Villegas A, Daniel D, et al; PACIFIC Investigators. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350. doi: 10.1056/ NEJMoa1809697.