Brian Henick, MD, associate director, Experimental Therapeutics, director, Translational Research in Aerodigestive Cancers in Medical Oncology, Columbia University Herbert Irving Comprehensive Cancer Center, discusses the 3-year updated data from a phase 2 trial (NCT02716038) investigating treatment with neoadjuvant atezolizumab (Tecentriq) plus chemotherapy in patients with resectable non–small cell lung cancer (NSCLC).

 focused on the 3-year updated survival data, Henick begins, adding that the pathological end points had already been reported in 

 in May 2020. Data showed neoadjuvant atezolizumab plus chemotherapy elicited a 3-year disease-free survival (DFS) rate of 49% and a 3-year overall survival (OS) rate of 77% in the 30 patients treated on the study, Henick explains. These outcomes compare similarly, if not favorably, to some of the previous findings from other studies that investigated the early administration of immunotherapy before or after the surgery for patients with NSCLC, Henick says.

Additional findings showed that there was a correlation between radiographic response and pathologic response, which was expected Henick continues. Although investigators observed major pathologic responses (MPRs) in 17 patients, there was not a statistically significant correlation between MPR and DFS and OS, Henick says. However, there was a significant association for pathologic complete response and survival, Henick adds.

Notably, of the 6 patients who developed brain metastases, 5 of these patients ultimately died with a median time to recurrence of 12.4 months and a median time to death of 45.3 months, Henick concludes.

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Brian Henick, MD, discusses the 3-year updated data from a phase 2 trial investigating treatment with neoadjuvant atezolizumab plus chemotherapy in patients with resectable non–small cell lung cancer.

Dr Henick on the Use of Neoadjuvant Atezolizumab Plus Chemotherapy in NSCLC

Brian Henick, MD, associate director, Experimental Therapeutics, director, Translational Research in Aerodigestive Cancers in Medical Oncology, Columbia University Herbert Irving Comprehensive Cancer Center, discusses the different ways to identify biomarkers of immunotherapy response in patients with lung cancer and how refining these approaches may improve individualized treatment approaches in the future.

Currently, the methods for localizing PD-L1 in tumors vary depending on the tumor type, Henick says. For instance, in lung cancer, the tumor proportion score (TPS), which focuses on identifying PD-L1–expressing tumor cells, is a common method, although some lung cancer immunotherapy biomarkers can also be found using a combined positive score (CPS) that localizes PD-L1 among other biomarkers, Henick explains. Additionally, atezolizumab (Tecentriq) is often administered to patients with lung cancer based on a score combining PD-L1 expression in both tumor cells and immune cells, Henick notes. Although lung cancer has several effective biomarker identification strategies, in tumor types beyond lung cancer, such as esophageal cancer and head and neck cancer, the CPS is the most useful for identifying biomarkers, Henick emphasizes.

A better understanding of the implications of PD-L1 expression in different immune cell subsets may allow for more refined biomarker identification processes across PD-L1–expressing tumor types, Henick says. For example, a study that measured PD-L1 expression through multiple methods found that most PD-L1 expression in patients with non–small cell lung cancer occurred in tumor-associated macrophages. In that cohort of patients, the level of PD-L1 expression in CD68+ macrophages was associated with PD-L1 levels in tumor cells and may be predictive of response, indicating a connection between high PD-L1 levels in the macrophages and patient response to immunotherapy.

In addition, novel biomarkers, such as a PD-L1 tumor infiltrating lymphocyte subset that can predict immunotherapy response independently of PD-L1 status, may be useful for predicting immunotherapy response going forward, Henick notes. As clinicians and researchers gain a clearer understanding of PD-L1 and other biomarkers, they may be able to use them to determine optimal treatments for individual patients, Henick explains. However, this is still an ongoing research field, and many of these biomarkers and detection methods need to be validated with prospective data, Henick concludes.

Brian Henick, MD, discusses the different ways to identify biomarkers of immunotherapy response in patients with lung cancer and how refining these approaches may improve individualized treatment approaches in the future.

Dr Henick on Biomarker Detection in Lung Cancer

Brian Henick, MD, medical oncologist, associate director of Experimental Therapeutics, director of Translational Research in Aerodigestive Cancers in Medical Oncology, the Columbia University Herbert Irving Comprehensive Cancer Center, discusses the importance of further exploring biomarkers in the immune microenvironment for immunotherapy in patients with lung cancer.

Although there has been a plethora of research and discourse surrounding PD-L1’s role in the use of immunotherapy in patients with lung cancer, given that it is the only go-to biomarker currently available, it is important to expand on the knowledge of biomarkers in the tumor microenvironment to get to the next level of understanding, predicting, and improving upon current treatments that are available for patients, Henick explains. Levering the knowledge of immunology currently available could help create research paths to better understand how these treatments could best be applied to patients, Henick adds.

The context of biomarkers also needs to be taken into consideration in future research, Henick continues. Context can include the patient-specific factors, such as race and ethnicity, that can impact how the immune system responds to a tumor, Henick notes. Important context to consider also includes tumor histology and the driver mutation status, Henick says, noting that differences can be observed with respect to immune cell composition and tumor type.

Immune cells are present within the tumor and their functional capacity also need to be considered, since there is likely a degree of interplay between these 2 aspects of the biology, Henick says. Taking into account what cells are present, who the patient is, and the tumor type can all play roles in determining the timing and choice of therapy. Understanding the relationship between these complex factors could help lead to an improved predictive and prognostic capacity for immune cell subsets, Henick concludes.

Brian Henick, MD, discusses the importance of further exploring biomarkers in the immune microenvironment for immunotherapy in patients with lung cancer.

Brian Henick, MD

Articles

Dr Henick on the Use of Neoadjuvant Atezolizumab Plus Chemotherapy in NSCLC

Dr Henick on Biomarker Detection in Lung Cancer

Dr. Henick on Further Exploring the Immune Microenvironment in Lung Cancer