During a WCLC 2022 session titled, “Clinical Issues with Immunotherapy in Non-Small Cell Lung Cancer,” four experts discussed some of the issues clinicians face when making prescribing decisions related to immunotherapy in patients with non-small cell lung cancer (NSCLC).
Filiz Oezkan, MD, of the West German Lung Center, Essen, Germany, started the session with a discussion of first-line choices in patients with PD-L1 positive disease. Dr. Oezkan walked attendees through data from several trials exploring chemotherapy versus immunotherapy, immunotherapy plus chemotherapy, and immunotherapy combined with other therapies.
Currently, single-agent immunotherapy has been approved for patients with NSCLC with a PD-L1 expression of 50% or greater, Dr. Oezkan said. Approved checkpoint inhibitors in the first line include pembrolizumab, atezolizumab, cemiplimab, and, in combination in patients with PD-L1 expression of > 1%, nivolumab plus ipilimumab.
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Studies have shown that the higher the PD-L1 expression, the better the reduction in the target tumor size, progression-free survival (PFS), and overall response rate (ORR) in patients treated with cemiplimab monotherapy. Intriguingly, he added, there is a higher mortality observed in the first year of single-agent immunotherapy, which is even higher in patients with <50% PD-L1 expression.
Median overall survival, PFS, and ORR are higher in patients with NSCLC with PD-L1 expression of 50% or greater treated with chemo-immunotherapy compared with single-agent immunotherapy. In addition, for patients with PD-L1 expression between 1% to 49%, chemo-immunotherapy is preferable.
“When we do our clinical decision making in first-line treatment, we should also consider renal insufficiency, liver insufficiency, and pre-existing autoimmune conditions, which may limit treatment options for both chemotherapy and immunotherapy treatments,” Dr. Oezkan said.
Next, Delvys Rodriguez Abreu, MD, PhD, of Hospital Universitario Insular de Gran Canaria, Spain, discussed first-line choices in patients with PD-L1 negative disease, which is estimated to occur in about 30% of patients with NSCLC.
Dr. Rodriguez-Abreu discussed the large number of trials exploring treatment options in this patient population. He summarized their findings by saying that for those with PD-L1 expression below 1%, chemotherapy combined with anti-PD-(L)1 or a combinatorial approach using anti-PD-(L)1/CTLA-4 immunotherapy is standard of care.
There is an ongoing need for new immunotherapy combinations based on translational science and new academic clinical trials to answer clinical questions, Dr. Rodriguez-Abreu said.
Next, Keunchil Park, MD, PhD, of Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, discussed second-line options in immune-pretreated patients.
“With increasing use of immune checkpoint inhibitors in the clinic, we all know that the majority of patients will develop resistance and progress over time,” Dr. Park said.
National Comprehensive Cancer Network (NCCN) recommended therapies in this patient population include only chemotherapeutic agents. There are currently no monotherapy or combination immunotherapies recommended by the NCCN.
Looking ahead, there are several hundred trials looking at this patient population, but none of them are biomarker-based, Dr. Park said. Instead, they use an “agnostic” approach with limited effect.
“To achieve real precision oncology, we need robust biomarkers with better understanding of specific resistance mechanisms including comprehensive genomic profiling and immune gene signatures,” Dr. Park said, adding that this research should also include continued monitoring of immune markers.
Finally, Francesco Passiglia, MD, PhD, of University of Turin, Italy, discussed immunotherapy in oncogene-addicted NSCLC.
“The use of next-generation sequencing molecular testing in advanced NSCLC has dramatically increased the number of targetable molecular alterations,” Passiglia said. “There is no doubt that for those patients with a driver mutation, if we have an approved targeted therapy, we want to give that upfront.”
Most oncogene-addicted tumors are associated with a tumor suppressive microenvironment that limits activity of immunotherapy. Because of that, clinicians must consider how to sequence immunotherapy and targeted agents.
“An immune checkpoint inhibitor given before a targeted therapy may increase the risk of high-grade toxicities in our patients,” Dr. Passiglia said. “The key message here is that we should always await molecular testing results before we start immunotherapy in our patients and then prioritize targeted therapy over immunotherapy any time we find an alteration that has a targeted agent available in clinical practice or in the context of a clinical trial.”
Single-agent immunotherapy should be reserved for later lines of treatment in most of these patients.
“We are waiting for the final results of prospective, ongoing clinical trials that—in the next month or year—will provide high-quality evidence to define the specific role of immunotherapy in the treatment of oncogene-addicted NSCLC patients,” Dr. Passiglia said.