Abstract IA24: Lung cancer: Disparities and implications for immunotherapy
Authors: Ramalingam Suresh S. 
Published: May 2016

Lung cancer is diagnosed in nearly 225,000 patients each year in the United States. Majority of the patients present with advanced stage of the disease at the time of diagnosis. This is a major impediment to improving cure rates for patients with lung cancer. Lung cancer incidence rate is higher in African American (AA) patients compared to Caucasian patients. In addition, AA patients have certain important differences from Caucasian patients with lung cancer. They are more likely to be diagnosed at a younger age with lung cancer and also have a higher prevalence of smoking-related lung cancer. AA patients are more likely to present with poorer prognostic features, have advanced stage disease, and experience delays in receiving therapy. Consequently, the improved outcomes achieved with various novel therapeutic modalities in lung cancer have not fully benefitted the AA patient population.

Systemic therapy is utilized for the treatment of nearly every stage of lung cancer. Platinum-based chemotherapy regimens have been used in all histological sub-types of lung cancer as cornerstone of therapy. In recent years, a greater understanding of molecular characteristics of lung cancer have led to the adoption of targeted therapies for certain patient subsets. Patients with an activating mutation in the epidermal growth factor receptor (EGFR) pathway are treated with specific tyrosine kinase inhibitors. Similarly, patients with the anaplastic lymphoma kinase gene rearrangement are treated with ALK inhibitors. The prevalence of EGFR mutation is variable based on racial background. Asian patients have higher mutation prevalence compared to Caucasian or AA patient population. We recently demonstrated that AA patients are less likely to harbor a driver mutation compared to Caucasian patients with lung adenocarcinoma. However, survival outcomes were similar for AA and Caucasian patients that were treated with a targeted agent for the specific mutation. Therefore, it is critical to conduct molecular testing in AA patients according to standard guidelines.

In 2015, the US FDA approved nivolumab, an immune checkpoint inhibitor for the treatment of advanced squamous cell lung cancer. In a phase III study, Nivolumab demonstrated an improvement in response rate, progression-free survival and overall survival compared to docetaxel in patients with advanced squamous cell lung cancer that had progressed on prior therapy with a platinum-based regimen. Improved efficacy was also observed with nivolumab in non-squamous histology relative to docetaxel. Pembrolizumab, another checkpoint inhibitor, has received approval for the treatment of advanced NSCLC in patients with PDL-1 expressing tumors. The advent of immune checkpoint inhibitors has provided an entirely new therapeutic tool for lung cancer. While this class of agents benefit patients with lung cancer, the response rate is approximately 20%, suggesting that biomarkers are needed for proper patient selection. Recent studies have suggested a higher likelihood of response to immune checkpoint inhibitors in patients with a higher mutation burden. The burden of somatic mutations appears to be different in AA patients with lung cancer. This is likely to have an impact on outcomes with immune checkpoint inhibitors in AA patients. Access to this new class of agents is also likely to be influenced by socioeconomic status, which will have a bearing on AA patients. Taken together, it is important to study the outcomes of AA patients with immune checkpoint inhibitors and overcome potential barriers that could limit their ability to derive maximal clinical benefit.

Citation Format: Suresh S. Ramalingam. Lung cancer: Disparities and implications for immunotherapy. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA24.