How to Handle Patients With PD-L1 >50% Non-Small Cell Lung Cancer

Leena Gandhi, MD, PhD, Dana-Farber Cancer Institute, discusses first-line treatment for patients with non-small cell lung cancer and PD-L1 > 50%, a topic she debated at the 2022 Great Debates & Updates in Lung Cancers meeting in New York.

In this debate, Dr Gandhi took the position that a combination of chemotherapy and an immune checkpoint inhibitor is currently the best treatment for this patient population and outlined the rationale for that position.

Transcript

I'm Leena Gandhi. I'm a thoracic oncologist and I direct the Center for Cancer Therapeutic Innovation at Dana-Farber Cancer Institute. I spoke today at the 2022 Great Debates and Updates in Lung Cancer meeting about the use of chemotherapy, along with immune checkpoint inhibitor therapy in first-line treatment of non-small cell lung cancer. We debated the relative benefit of pembrolizumab monotherapy or immune checkpoint inhibitor monotherapy versus combinations with chemotherapy and immune checkpoint inhibitor therapy.

Unfortunately, we don't have direct comparative data to not have those kinds of debates, but I think there is certainly a concern that immune checkpoint inhibitor monotherapy, even in high PD-L1 expressing patients, may not be sufficient for the group. We know that the response rates are less than 50% overall and that many patients experience disease progression early in the course of that therapy. In fact, the patient data shows that they perform worse than chemotherapy, at least initially.

Understanding which patients are most likely to benefit from the combination and which patients should receive monotherapy is the holy grail for our field. However, until we have that data, there are certain risk groups of concern that may not benefit from pembrolizumab monotherapy, including those who have nonsmoking-related oncogenic drivers, those who have STK11 mutations, and those who have large symptomatic burden or large tumor burden. The risk for those latter groups occurs if patients don't go on to receive second- or third-line therapy, because they've missed the chance for long-term benefit from initial therapy if we don't include what we hope will produce the maximum potential benefit.

There are a lot of reasons to consider combining chemotherapy with immune checkpoint inhibitor therapy. Chemotherapy can, we know, increase antigen presentation, increase T-cell inflammation, decrease – in some circumstances – regulatory negative factors, and increase innate immunity. There is a lot of rationale to think about with that combination. Certainly, we have seen from those combinations not only good response rates, but also long-term durable response rates for many patients. Until we know more about which groups and which specific kinds of patients can forego chemotherapy and receive monotherapy, I think we'd all rather get as much benefit to as many patients as we can. I think we should try to think more along the lines of combination therapy until we have more data.

Source

Gandhi L. Debate: How to Handle PD-L1 > 50% - Use pembrolizumab + Histology Specific Chemo. Presented at: Great Debates & Updates in Lung Cancer; October 14-15, 2022; Brooklyn, New York.