A welcome respite from the city heat and concern about the pandemic was sitting in my NYC apartment watching Part 2 (June 22-24) of the AACR 2020 Annual Meeting. This, as was Part 1, was a virtual meeting. I am warming up to the virtual meeting format because it enables people from all over the world to attend without paying exorbitant hotel fees and plane fares. AACR Part 2 had several interesting sessions, and I am summarizing them here in four main themes.
Early detection and Interception: LUNGevity Scientific Advisory Board Member Dr. Lecia Sequist chaired a fantastic session on how current low-dose CT screening for lung cancer is not adequate in capturing all lung cancers. Furthermore, Dr. Sequist pointed out that the current USPSTF screening guidelines may in turn not adequately capture all those at risk of developing lung cancer. Several groups are thinking of developing blood-based tests to complement LDCT. These blood tests could be used to identify those patients who would benefit from LDCT. One such test is the “lung cancer likelihood in plasma (Lung-CLiP)” test, which can detect circulating tumor DNA (ctDNA) in the blood. This test was found during its development to be able to distinguish between early-stage lung cancer patients and cancer-free control patients, but not always. This is because ctDNA from both early-stage NSCLC patients and non-cancer controls contain mutations. The Lung-CLiP ctDNA test is able to identify ONLY cancer-specific mutations for early detection.
We also heard from the laboratory of LUNGevity Career Development Awardee Dr. Jennifer Beane. They reported that whereas pre-cancerous lesions from both adenocarcinoma and squamous cell lung cancer (two different types of non-small cell lung cancer) show changes in two specific types of immune cells, neutrophils and macrophages, only squamous cell lung cancer showed changes in a specialized immune cell called dendritic cells. These cells are important parts of the anti-cancer immune response. Dr. Beane’s research shows that adenocarcinoma and squamous cell lung cancer may have different immune cell profiles, and this has implications for how we target these cancers with immunotherapy.
Understanding resistance to targeted therapies: There were several presentations dedicated to monitoring and understanding how lung cancer cells escape the effects of targeted therapies. Analysis of ctDNA from patients treated with a MET inhibitor (tepotinib) in the VISION trial showed that a liquid biopsy can be used to monitor the evolution of the disease. More importantly, the liquid biopsy accurately detected MET Exon 14 skipping mutations or MET amplifications in the plasma pf patients. This has potential implications in screening patients for participation in MET drug trials given that the MET patient population tends to be elderly; a liquid biopsy test may be more convenient to screen these patients.
Another trial that was discussed at AACR Part 2 is the TATTON trial: a combination therapy trial designed for those patients who become resistant to osimertinib (Tagrisso®) by developing a MET amplification, which can then be targeted by savolitinib. Results of ctDNA analysis from the TATTON trial showed that those patients who cleared the mutant EGFR DNA from their blood were more likely to respond to the combination, suggesting that this may be an effective way to monitor response to the combination.
I really enjoyed a presentation discussing mechanisms of resistance to MRTX849 – a drug that blocks a specific KRAS mutation, the G12C mutation. We finally have drugs in clinical development that can block the G12C mutation. It was exciting to see that scientists are proactively researching mechanisms of resistance to these drugs in order to stay one step ahead. As we know, resistance to targeted therapies is inevitable, so the more forward-thinking we are, the better it is for patient outcomes.
COVID-19: As expected, there were several sessions on COVID-19. One of the sessions focused on the immune aspects of the disease: what the SARS-CoV-2 virus does to the immune system and how the immune system responds to the infection. Studies conducted in patients infected with SARS-CoV-2 suggest that CD8 T-cells (specialized immune cells that fight virus infections and cancer cells) are reduced in COVID-19 patients. Interestingly, patients seem to produce large number of plasmablasts (specialized B-cells that produce antibodies). While these findings were not discovered in cancer patients per se, they have important implications in cancer immunotherapy because both T- and B-cells are involved in anti-tumor response.
The other COVID-19 session was on health disparities and how the pandemic has disproportionately affected people of color and the underserved. Lessons from NYC suggest that Black/African American patients and Hispanic/Latino patients are more likely to be hospitalized and more likely to succumb to COVID-19 than White patients. These disparities have also been documented in other states, such as Florida and California, with a high Hispanic/Latino population. The CDC notes that racial and ethnic minorities are especially vulnerable, given their living situations (such as residential segregation), work conditions (much lower likelihood of having the option to work from home), higher prevalence of chronic health conditions, and lower access to healthcare.
Health Disparities: These sessions were probably the highlight of AACR Part 2. I commend AACR for including discussions on several areas of health disparities, such as disparities in the healthcare/cancer researcher workforce and disparities in cancer care. AACR Part 2 brought together an outstanding panel of experts who represented diversity in the healthcare workforce, from industry to academia to medicine. The panelists discussed systemic barriers such as institutionalized racism that have traditionally impeded people of color from attaining admission into graduate programs and positions of leadership and authority in organizations. It was refreshing to hear such candid conversations about social justice and how it links to health equity and equal access to care for all. As Dr. Ned Sharpless pointed out, “Disparities in NIH funding for cancer researchers from underrepresented communities need to be fixed. Otherwise, we will miss out on their creative genius.”
I also appreciated the session on clinical research and inclusiveness. Clinical trials have not been successful at reaching communities of color. This is of concern for two reasons: the first is the issue of access (clinical trials are a source of life-saving anti-cancer therapies) and the second is a question of biology (whether the same drug acts differently in different populations). Lessons from multiple myeloma (a type of blood cancer) indicate that drugs may behave differently in African American community members, suggesting a different biology of the disease. While such studies have not been done in lung cancer, the same may hold true. In terms of recruitment to clinical trials, several institutions, such as the University of Texas Southwestern Medical Center, have done a great job in reaching the unreached. A take-home conclusion was that increasing awareness about clinical trials is NOT sufficient to increase enrollment of minority communities. We need to proactively promote facilitators (such as trust in the doctor and trust in the clinical trial center) and decrease barriers (such as travel cost/health insurance and lack of cultural sensitivity).
The past three months have been marked by three landmarks for me as a scientist and a patient advocate: a global pandemic, three virtual scientific meetings (AACR Part 1, ASCO, and AACR Part 2), and 10 drug approvals for lung cancer. All three have left me with one message: we need to work together to beat lung cancer, no matter the adversity we face! I am looking forward to the next virtual scientific meeting, dedicated exclusively to the impact of COVID-19 on cancer, the “COVID-19 and Cancer” meeting organized by AACR.
- Updates from the Annual American Association of Cancer Research Meeting, Part 1
- ASCO 2020 and recent lung cancer drug approvals: What it all means for patients
- Navigating the Cost of Comprehensive Biomarker Testing
Dr. Basu Roy is LUNGevity's Vice President of Research.