Last weekend, close to 40,000 oncology professionals, including superstar lung cancer researchers (many of whom are members of LUNGevity’s Scientific Advisory Board), gathered in Chicago to attend the annual meeting of the American Society of Clinical Oncology, or ASCO.
This year, the conference was dominated by studies focused on immunotherapy, disease treatments that leverage the body’s natural immune response. The field of immunotherapy is bursting with options. The breakthroughs from this new approach to disease management flow into research for the treatment of lung cancer. Below I have summarized highlights from the 2018 ASCO conference.
Immunotherapy has been found to be effective in tumor cells expressing high levels of the protein PD-L1. However, PD-L1 is not always a reliable biomarker because it tends to fluctuate over time, and some areas of the tumor may express more PD-L1 than other areas. Also, tumors that do not make PD-L1 protein can still respond to immunotherapy.
With this in mind, researchers have been working to optimize the biomarkers used to predict which patients will benefit from immunotherapy. They found that measuring the tumor mutational burden (TMB), the number of mutations in the tumor DNA, may be a promising approach to predicting patients’ responses to immunotherapy. Sometimes TMB may be used in conjunction with PD-L1 levels to provide guidance for cancer treatment.
One important phase 3 clinical trial looked at bevacizumab (an anti-cancer drug known to reduce the tumor’s ability to promote blood vessel growth required to feed the cancer) in patients with advanced non-squamous non-small cell lung cancer (NSCLC). The initial results showed that adding atezolizumab, an immunotherapy drug, to bevacizumab and carboplatin/paclitaxel (two chemotherapy drugs often used as doublet treatment) decreased cancer progression and increased overall survival, compared with the same regimen without the immunotherapy. While more research is needed, this study also raises hope for patients with EGFR-positive and ALK-positive NSCLC. The trial results note that patients who have shown progression on an EGFR tyrosine kinase inhibitor (TKI) or an ALK TKI responded well to the combination approach of bevacizumab with doublet chemotherapy and atezolizumab.
Another key phase 3 clinical trial studied the effect of adding an immunotherapy agent to the current recommendation for first-line treatment of advanced squamous NSCLC. Researchers found that when the immunotherapy drug pembrolizumab was added to doublet chemotherapy, the patients saw a significant increase in overall survival. This study is likely to result in a change in the current guidelines for first-line treatment of patients with advanced squamous NSCLC.
Many different clinical studies are underway to determine the optimal combination of lung cancer treatments (including immunotherapy, chemotherapy, targeted therapy, and radiation). Also, research is being conducted to identify the optimized sequence of treatments to enhance patients’ survival rates and quality of life.
Non-Small Cell Lung Cancer with driver mutations
Lots of progress is also happening for NSCLC with driver mutations! In a phase 1 clinical trial, patients with advanced NSCLC who were positive for RET-fusions had very promising results with the drug LOXO-292, which selectively targets RET-fusion proteins. Additional studies are planned to further develop this treatment option.
Small Cell Lung Cancer
Excitement around Rova-T continues. LUNGevity’s Scientific Advisory Board member David Carbone, MD, PhD, at Ohio State University, presented phase 2 clinical trial results showing that the protein DLL-3, which is found at high levels only in small cell lung cancer (SCLC) tissue and not in healthy tissue, could be the first targeted therapy for advanced SCLC. The results showed that Rova-T, which binds to DLL-3, improved overall survival for SCLC patients whose cancer had returned after chemotherapy. In addition, scientists are exploring the potential of immunotherapy in SCLC. Data from a phase 2 clinical trial suggests that pembrolizumab may be effective in SCLC patients who have progressed on chemotherapy and whose tumors are positive for the PD-L1 protein.
And finally, progress with liquid biopsies continues in the field of early detection. When someone develops cancer, their blood often contains pieces of the mutated DNA that escape from dying tumor cells. Tumor DNA found in the blood is often called circulating DNA (ctDNA) or plasma cell-free DNA (plasma cfDNA). Recently, liquid biopsy tests have become available to analyze ctDNA and determine whether a patient has cancer and, if so, what type of cancer. The results of a study presented at ASCO suggest the technique may also be used for detecting early-stage lung cancer. The researchers are developing the Circulating Cell-free Genome Atlas (CCGA) aimed at understanding how liquid biopsies can be used for early detection and complement CT screening. More research is underway in the hopes of developing this technique into a useful, lifesaving tool for the early detection of lung cancer.
In his presidential address, ASCO President Dr. Bruce Johnson mentioned that “we are close to being able to treat half of our patients with NSCLC with targeted therapy or immunotherapy as their initial treatment.” We are encouraged by the progress we saw at ASCO this year, and we are confident that the next year will bring even more.
Juhi Kunde, MA, is a science writer for LUNGevity.