Pembrolizumab +/- Chemotherapy in Lung Cancer: Reading Between the Studies

Mark G. Kris, MD


December 30, 2021

This transcript has been edited for clarity.

This is Mark Kris from Memorial Sloan Kettering. I'm making the first of, hopefully, an ongoing series of presentations entitled "Reading Between the Studies."

What do you do when you need information and you look to clinical trials to give you that information to care for an individual patient, but you don't find a trial that is exactly on point?

One of these situations is a common one: [What is the role] of chemotherapy with a checkpoint inhibitor in patients with lung cancers that have programmed death-ligand 1 (PD-L1) expression greater than 50%? There is universal agreement that these patients, unless there's a contraindication, should receive a checkpoint inhibitor. But who in that group could also benefit from chemotherapy?

I was kind of surprised to note that there are no clinical trial data that are available to guide this decision. What we're really forced to do is to look at the trials that exist now, including trials of chemotherapy vs pembrolizumab alone and also trials of chemotherapy vs the combination of chemotherapy and checkpoint inhibitor — in this case, pembrolizumab. I know this is not an ideal comparison, obviously it's cross-trial comparison and you don't want to do that, but this is a situation we're all faced with on an almost daily basis. We need to take the information that's out there. What does the information from the two trials show?

Looking at, number one, what I think is most important — progression-free survival. Getting a checkpoint inhibitor alone led to a median progression-free survival of approximately 8 months and progression-free survival at 2 years of 23%.

In a related trial looking at chemotherapy and a checkpoint inhibitor in the same group of patients with high PD-L1 expression, the median progression-free survival was 11 months and the 2-year progression-free survival was 31%. There was clearly an improvement in both median and 2-year progression-free survival.

I like progression-free survival because those are the patients who are going to derive the most benefit. Progression free generally means symptom free, or new symptom free, and also, that puts them in the population of patients that can have very long survival, or perhaps even cure. To me, that's the most important criteria — progression-free survival or variations on that such as event-free survival.

What about overall survival? Well, there, the results are pretty comparable, actually. The median overall survival in the trial giving pembrolizumab alone vs chemotherapy was 30 months, and it was 28 months in the, I'll call it, parallel trial giving chemotherapy plus the checkpoint inhibitor in that group. The 2-year survival was 52% — actually the exact number in both trials — in chemo plus and pembrolizumab alone.

What about the response rate? There, too, was a clear improvement. It was 45% with pembrolizumab alone and 62% [with the combo].

How do you handle these data? Well, I think first off, either approach is correct. It's data driven. It's in guidelines. There's FDA approval for both of these approaches. I think either of them is fine.

There is clear benefit, though, to me in progression-free survival and in rates of response. That translates into use in two groups of patients: those patients who want the maximum treatment that can be given to try to give them the longest progression-free survival and the best chance of being cured of their cancer. For those patients who choose that, in those patients where it's safe, I'll give both drugs. Also, for patients who have a greater degree of symptoms, clearly having a higher rate of response means better control of symptoms.

When we don't have direct clinical trial data to guide us, we do have to interpolate, extrapolate, and we do have to, I'll call it, read between the lines of trials where the data are not there to guide us. This is the best we can do.

Eventually, I think we're going to have clinical trial data here, but I hope this analysis of these data helps you in making the choice of giving a checkpoint inhibitor alone or a checkpoint inhibitor plus chemotherapy for patients with lung cancers and high PD-L1 expression.

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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