I have a huge soft spot for the annual AACR meeting. Back in my graduate school days, the annual AACR meeting was the largest global gathering of basic cancer researchers. With over 23,000 attendees this year, it still is—except that the meeting has evolved over the years to include more and more clinical research to answer the fundamental question: How can we truly build upon our knowledge of basic science to impact patient care? The 2019 annual meeting takes this question a step forward, as evident from this year’s meeting theme.
With immunotherapy becoming mainstream over the past few years, we are now learning more and more about which populations benefit from it. Research from Dr. John Heymach’s group at MD Anderson shows that mutations in a gene called LKB1/STK11 predict which patients may respond to immunotherapy. The group had previously shown that lung cancers with both KRAS and LKB1/STK11 mutations do not respond well to immunotherapy. Building on these findings, the team presented data that showed that mutations in the LKB1/STK11 gene predict which patients will respond to chemotherapy-immunotherapy combinations. New research presented at AACR shows that tumor mutational burden, or TMB (the total number of mutations found in the DNA of cancer cells), is emerging as a possible predictor of response in patients who have received either monotherapy or combination immunotherapy (anti-PD-L1 and anti-CTLA4 immunotherapies) in the 1st-line setting. Last but not least, we saw new data that demonstrates that chemotherapy-immunotherapy combinations may provide benefit to patients with liver or brain metastases whose cancers do not have any targetable mutations. This is an important finding, given that these patients have limited treatment options.
Lots happening on the targeted therapies front as well. The meeting included presentations by Dr. Alice Shaw from Massachusetts General Hospital and Dr. Lecia Sequist from Harvard Medical School and Massachusetts General Hospital Cancer Center on what’s next for ALK and EGFR targeted therapies. ALK-positive lung cancer patients now have access to 3rd-generation ALK therapies. However, the cancer inevitably recurs because cancer cells figure out ways to escape the effects of these therapies. Comprehensive biomarker testing of resistant tumors has helped us understand that cancer cells outsmart ALK inhibitors either by developing additional mutations in the ALK gene or switching on other pathways. Now that this is understood, scientists are working to develop 4th-generation inhibitors that block these new mutations and are testing new combinations of drugs that can block these new pathways. The same is true for EGFR-positive lung cancer. A new drug, savolitinib, is showing promise in patients who have progressed on EGFR-blocking drugs. Savolitinib works by blocking the MET gene that is often turned on in cells treated with EGFR tyrosine kinase inhibitors. Around twenty-five percent of patients who progress on drugs such as osimertinib may have changes in the MET gene. We are also seeing progress in treatment development for other mutations, such as ROS1. The current standard of care for ROS1 is crizotinib. This drug does not enter the brain. Newer drugs, such as entrectinib, are showing promise in ROS1 patients who have never received a treatment or have progressed on crizotinib. Entrectinib is effective in patients with brain metastases.
We are also making progress in using liquid biopsies as well. Liquid biopsies, non-invasive blood tests that check for the presence of cancer DNA or cancer cells in the blood, are being used to check for the presence of actionable mutations in situations in which tissue biopsies are not an option. At this meeting, we saw data from a clinical trial specifically designed to check whether tissue and liquid biopsies are comparable. Preliminary results from the trial indicate that liquid biopsies correctly detect mutations, such as EGFR and ALK, for which drugs exists. These findings are especially important because they clearly establish that liquid biopsies may be accurate enough to decide treatment for patients with metastatic non-small cell lung cancer.
The icing on the cake at AACR was seeing more and more patient-founded and patient-driven oncogene-specific groups presenting. Both the EGFR Resisters and ALK Positive presented their work on how their groups are driving research by educating patients, informing clinicians and researchers, and helping identify unmet needs specific to their communities. I anticipate these groups playing more and more of a central role to lung cancer research.
Dr. Basu Roy is LUNGevity's Senior Director of Research.