Locally Advanced Lung Cancer: No Longer 'One Size Fits All'

Mark G. Kris, MD


July 08, 2022

This transcript has been edited for clarity.

I'm Mark Kris from Memorial Sloan Kettering, talking today about a topic that everybody seems to want to talk about, which is how to approach patients with locally advanced lung cancers and early-stage lung cancers who are candidates for surgery.

We suddenly have many different types of approved therapies, and folks just want to know what to use for each individual patient. Unfortunately, there's no quick answer to this. It is a large amount of hard work and talking to figure out what to do. You absolutely need to spend the effort to work with all the different specialists in the field to decide what is best for an individual patient. It's hard. Anybody in the medical field knows how difficult it is to have a quiet, thoughtful conversation with a colleague now. You just have to make that happen, though.

My first recommendation to everybody dealing with these patients is to do your best to get all the best minds available in your facility to make a good decision. It's critical and central to have the surgeon lead because only the surgeon can truly decide if a person is operable and resectable, and those are kind of the entry criteria to these discussions. Is the patient operable? Is the patient resectable? Let the surgeon decide. We can take part in that decision, but the surgeon has to decide.

From the patient's standpoint, it's absolutely critical to achieve a complete resection. When you look at all the data about how people do with early-stage lung cancer, the ones that have complete resections are the patients with long survival and cure. You have to get a complete resection. Anything that can be done to achieve that, you must take that step to have a complete resection.

We know that even with complete resections, patients recur. Nowadays, with great surgery and better technique, the recurrence is almost always metastatic and systemic. To improve upon the results with a successful surgery, we must add a systemic therapy. Suddenly, we have chemotherapy, targeted therapy, and immunotherapy all on the table, and they all are approved for patients with early-stage lung cancers. What do we do?

It's important that we understand that chemotherapy is part of the mix for virtually every patient where it's safe. For all but the tiniest lung cancers, cisplatin-based chemotherapy is on the table. When you look at these recent trials of adjuvant immunotherapeutics and targeted therapies, all patients were planned to get chemotherapy. Not all did, but cisplatin-based chemotherapy was planned. That's part of the mix, and we need to find a way to try to get cisplatin-based chemotherapy into the patients.

When it comes to immunotherapeutics, I think it's pretty clear when you look at the available data, particularly in the adjuvant setting, that these are patients who have expression of programmed death ligand 1 (PD-L1). The other thing is that they don't have a target. The trials of immunotherapeutics in the perioperative setting generally excluded people who had EGFR and ALK mutations, and I would extrapolate from that, probably any target other than KRAS G12C.

If you have a target, immunotherapy is probably not the best thing for you. When you look at the data in the subgroups, it show that with targeted therapies, immunotherapeutics are of limited or very small benefit, even in the setting of high PD-L1.

What I'm getting at is the need to test patients. You need to know whether they have a target. If they have a target, in addition to chemotherapy, you have to think of a targeted therapy. If they don't have a target and have expression of PD-L1, you have to think of an immunotherapeutic.

What's the order? I'm a huge proponent of neoadjuvant therapy. I think it's critically important to be able to assess whether a treatment is helping and to decide whether to continue it or discontinue it. Now, we have regimens of neoadjuvant therapies, particularly for immunotherapeutics, with the recent approval of nivolumab and chemotherapy.

Please don't forget postoperative radiation therapy. It clearly cuts down on recurrence in the mediastinum, and it's twice as good as not receiving postoperative radiotherapy. It also plays a role in improving outcomes. It's not a huge role. It's less than a 12% improvement in disease-free survival at 3 years, but it's a significant one. Please remember, chemotherapy is a 5% improvement in 5-year survival and we routinely use that.

In summary, there is no one-size-fits-all anymore. It's important to put your team together. It's important to have a really good dialogue about what's best for the individual patient. It's important to test patients. You need to know if they have a driver because that sets the stage for either an immunotherapeutic or a targeted therapy.

Don't forget postoperative radiation therapy. Get your radiation oncologist involved to see if a plan can help that patient with mediastinal disease. Obviously, it's for N2 disease, not for others.

We have many new tools now. There are several questions remaining, but there is a huge opportunity to do better for our patients with locally advanced lung cancers.

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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