Dr Matthew Gubens Highlights Immunotherapy Advances and Combinations for Lung Cancer

Recent research has shown the potential of immunotherapy treatments for treating lung cancer, explained Matthew Gubens, MD, MS, assistant clinical professor of thoracic oncology at the University of California, San Francisco. Dr Gubens also spoke about oncologists’ hopes for using immuno-oncology (IO) agents in combination with one another or with chemotherapy.

Transcript (slightly modified)

What are some recent advances in immunotherapy treatments for lung cancer?

Two years ago, of course, we got the information that led to the approval of nivolumab, pembrolizumab, and then later atezolizumab for the second-line use in non-small cell lung cancer. Last year at ESMO, we heard about Keynote-024, which told us that for those who have PD-L1 expression over 50%, pembrolizumab actually is superior to chemo, not just in terms of PFS [progression-free survival], but also overall survival for that subset of patients.

That has really changed practice. It makes it incumbent upon us to look for PD-L1 expression in all of our patients up front, and to treat accordingly. I think that’s probably the most exciting thing that’s happened in the last year, and now we really have opportunity for patients either to get PD-1 or PD-L1 therapy in the first line, as appropriate, and for everybody else in the second line.

What is the role of combination immunotherapies in lung cancer?

To be determined. This is really an exciting area, and as I said, a couple years ago we got second-line use, then we got first-line use single agent, but we still know that even as exciting as first-line pembrolizumab is, response rates are still under 50%. How can we augment that? How can we help responders respond better and more durably, but also, how can we help the non-responders respond? As exciting as it is to have the second-line use, response rates are still 15% to 20% in all comers.

So I think these combination studies, first of all, are coming fast and furious. There are literally dozens you can find on ClinicalTrials.gov. The couple that are maturing the fastest are chemo and PD-1 combinations, and certainly at ESMO we saw some updated information from a phase 2 trial that looked at carboplatin pemetrexed with or without pembrolizumab, and really showed improved response rate in this randomized trial, as well as prolonged PFS. There are phase 3 data coming, so obviously I think all of us want to see the more rigorous data before we make decisions about that, but this idea that maybe chemo and PD-1 inhibition may work together, something that maybe you wouldn’t have thought about a few years ago, but certainly this kind of antigen release from cancer therapy may actually help.

The other piece we’re really excited about are IO/IO combinations. Certainly melanoma has led the way, and we know that using PD-1 or PD-L1 plus CTLA-4 inhibition really has been almost synergistic in that patient population. So now we’re waiting very eagerly for some of the phase 3 results to report out for either ipilimumab and nivolumab, or tremelimumab and durvalumab. At ASCO last year we saw some very provocative data that for PD-1 expression, there seemed to be a higher response rate when you added the CTLA-4 inhibitor. So I think we’re very eager to see the really rigorous phase 3 randomized data come through.

Then of course, both of these issues of combinations raise even more the issue of toxicity. One drug has a certain amount of toxicity, but the compound toxicity really will be a problem, and as we start using some of these combinations we really have to be very much looking out for these toxicities and engaging our multidisciplinary teams to manage those. So I think that’s really where we’re going in the next year of data that unfolds.

Aside from that, of course, there’s the whole next generation. Those were the first to the table because chemo was on the table and ipilimumab was already being used in melanoma. There’s all these other dozens of compound treatments that are very exciting, but the question will be: how do we separate the wheat from the chaff? How do we assign patients and how do we follow through to make sure that we choose combinations that are sensical and that actually have efficacy?