Checkpoint Inhibitors Have a Role for 'Virtually Every Patient'

Hello. I am Mark Kris from Memorial Sloan Kettering, reporting about an extraordinary week where the therapy of lung cancer has dominated the headlines, at least here in the eastern part of the United States.

This week, multiple trials were reported at the American Association for Cancer Research (AACR) 2018 Annual Meeting in Chicago. These trials included chemo plus pembrolizumab versus chemo,^[1,2] ipilimumab/nivolumab versus chemo,^[3] and atezolizumab plus bevacizumab plus chemo versus bevacizumab plus chemo.^[4] In all three trials there was a clear benefit with [use of] immune checkpoint blockers.

In a trial [published in the New England Journal of Medicine], a certain population of patients with high tumor mutation burden had a clear benefit for ipilimumab/nivolumab over chemotherapy.^[5] Another important trial also recently published in the New England Journal of Medicine was the use of neoadjuvant nivolumab.^[6]

These are extraordinary developments. I think, first and foremost, that there is now no patient with lung cancer in whom an immune checkpoint blocker does not have a role. Who would have thought that in just a few short years we would be saying that?

The other extraordinary observation is that there are virtually no patients with lung cancer who do not receive cell cycle-targeted cytotoxic chemotherapy in addition to an immune checkpoint blocker. Small cell adenocarcinoma, squamous cell carcinoma, early versus late stage—all of them get chemotherapy as well.

Choosing Optimal Combinations

I think that message number one from this week is that combinations are the cornerstone of our systemic therapies, and oncologists have to choose the best combinations for patients. That is our job. Here are a couple of thoughts on that choice.

You have all heard me say before that things have gotten so much better for our patients because there are many more therapies that can help them. But things have gotten so much harder for us because, not only are there more choices when making initial decisions, there are more decision points because our patients are living longer, and we have more medicines to offer them. That is a great thing and a challenge that I am very happy to take on.

The next point is that for all of these studies, there is more evidence of dependency on "immune mechanisms." The two that have been looked at most are PD-L1 expression and tumor mutation burden. The more you have, the more likely you will benefit from a checkpoint blocker. That makes sense because that is the mechanism of action of these drugs. When you make treatment choices, look for those determinants of benefit; the higher they are, the more likely you are going to have benefit.

A message from the IMpower150 study^[3] is: Do not forget bevacizumab. Bevacizumab clearly adds to benefit with chemotherapy. We have now shown that atezolizumab plus chemotherapy is improved by the addition of bevacizumab, at least in terms of overall benefit. Do not forget that drug.

Again, everybody gets chemotherapy. It may not be at the same time; it may be before and, perhaps in the case of small cell lung cancer, it could be after. It is incumbent upon us to use what we know about how best to treat patients with chemotherapy and refresh ourselves about optimal supportive care. The more modalities we give and the more drugs we put together in the treatment plan, the more complicated and complex supportive care and management of side effects will be. As oncologists, we have to be on our A game to make sure that we are doing the best for our patients. [We need to ensure] safe delivery of these agents, provide the best supportive care available to lessen adverse effects, and quickly identify and manage adverse effects.

We had a lot of developments this week in stage IV lung cancer. At another time, I want to spend a few moments talking about how we can take even further advantage of the immune checkpoint blockers. As for today, immune checkpoint blockers are part of the care of virtually every patient [with lung cancer]. We must work hard to find the best combinations for our patients and give them at the best time.

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