COMMENTARY

When to Add Chemotherapy to IO in Lung Cancer? New Data from ASCO 2020

Mark G. Kris, MD

Disclosures

July 22, 2020

This transcript has been edited for clarity.

I am Mark Kris from Memorial Sloan Kettering Cancer Center in New York, commenting on some of the abstracts from the 2020 virtual meeting of the American Society of Clinical Oncology (ASCO). I want to focus on studies on immunotherapeutics in lung cancer.

Here in the United States, if you have a lung cancer that does not have a molecular target, you get a checkpoint inhibitor, usually an anti–PD-1 or anti–PD-L1 drug. It doesn't matter if you have squamous cell, adeno-, or small cell lung carcinoma; everyone gets a checkpoint inhibitor, with or without chemotherapy. A number of trials presented this year give us additional information to inform our decision-making.

Ramalingam and colleagues reported data from a trial of ipilimumab (IPI) and nivolumab (NIVO) vs chemotherapy in the upfront setting. The outcomes with IPI/NIVO were better vs chemotherapy, but the important message from this trial is that the deep and persisting benefits you see with those agents continue to 3 years. Clearly, these drugs make a huge impact in patients in terms of the depth and permanence of responses. In my mind, this is the path to cure. I do believe some of these people can be cured.

A study by Reck and colleagues added chemotherapy to this IPI-NIVO combination. Overall survival was significantly better in patients who received the IPI-NIVO plus chemotherapy combination compared with chemo alone. How exactly that will be taken forward is unclear. We're still working our way through the decision about who receives chemotherapy in addition to checkpoint inhibitor therapy. But we now know that added chemotherapy improves outcomes.

The third study appears to be a negative trial, but the same message is there. Leighl and colleagues looked at the combination of durvalumab and tremelimumab plus chemotherapy versus chemotherapy alone. Folks that got the checkpoint inhibitor saw benefit that increased with the addition of chemotherapy. It is difficult to make cross-trial comparisons, but I can clearly see activity in this regimen. Is it the same as, better than, or worse than the combination of ipilimumab and nivolumab? It is difficult to say without a head-to-head comparison, but we can see activity here. This may give us the opportunity to use these new immunotherapeutic combinations and, with more data, learn how to make decisions about what to use for individual patients.

Again, there are no definitive answers from any of these trials, but they provide more information to help guide our decision-making. It is clear to me that adding chemotherapy improves outcomes somewhat; however, it also clearly adds toxicity. How you choose what to use becomes very patient-specific. In general, the more symptomatic the patient is and the greater their disease burden, the more it makes sense to add chemotherapy to the regimen. People need a response when they're having a lot of symptoms, and this is one way of achieving that.

The last presentation I want to mention is the study of the anti-TIGIT antibody tiragolumab by Rodriguez-Abreu and colleagues. There's been a quest for another immunotherapeutic agent that can be added to ipilimumab, nivolumab, tremelimumab, or the other checkpoint inhibitors. Many agents have been tried, but unfortunately, we've seen few successes. This trial appears to show a higher rate of response and a longer time to disease recurrence in those patients who received initial therapy with the anti-TIGIT antibody plus atezolizumab vs atezolizumab alone. I see a glimmer of hope that additional checkpoint inhibition can improve outcomes. Clearly, tiragolumab will be taken forward in future studies.

In summary, for immunotherapeutics from ASCO 2020, we received confirmation that we can make a significant impact on people's lives. These treatments can give them deep, durable responses that we hope will one day translate to cure. Our research effort to find additional immunotherapeutic agents is bearing fruit and hopefully will add drugs to our armamentarium.

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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