My takeaways: 2022 AACR Annual Meeting

Authors Dr. Kimberly Blackwell, Tempus Chief Medical Officer

The American Association for Cancer Research (AACR) Annual Meeting brings together some of the brightest minds in oncology to share critical knowledge and cutting edge scientific research. It’s an event that many of us in the cancer community look forward to each year, and with the return of an in-person meeting for the first time since 2019, this year’s event felt that much more momentous. But two years of virtual convenings never diminished this group’s commitment to driving progress against cancer, as evidenced by one of the themes of the 2022 AACR Annual Meeting: “Transforming Patient Outcomes.” 

The focus on patient outcomes resonated with me and my fellow colleagues attending AACR throughout the week. Tempus is on a mission to significantly improve patient outcomes, across disease areas, by applying data and AI to both therapeutic discovery and development as well as diagnostics. I’m proud to share that our team presented two posters demonstrating how Tempus’ comprehensive genomic sequencing capabilities generate high-quality DNA and RNA data that in turn empower clinicians to make informed, data-driven treatment treatment decisions. Additionally, our Chief Scientific Officer Joel Dudley PhD and Ameen Salahudeen MD, PhD, Scientific Director of Tempus’ modeling lab, delivered a product theater to a standing room-only crowd on applying real-world data and 3-D biological tumor modeling to translational research. 

The AACR Annual Meeting is a wonderful reminder of the oncology research community’s unwavering dedication to advancing science, treatments, and care for the 1 in 3 people who will be diagnosed with cancer in their lifetime. As I look back at the symposium, here are my key takeaways from some of the more impactful presentations:

The pathogenesis of cancer susceptibility due to inherited DNA repair defects

Dr. Michael R. Stratton, Wellcome Trust Sanger Institute | Cambridge, United Kingdom

In the first plenary presentation, Dr. Stratton highlighted how sequencing somatic mutations in normal cells led to discoveries in Colorectal Cancer (CRC) and CRC predisposition syndromes. His team sequenced colon tissue from a large number of individuals, then cataloged and summarized their findings into a landscape of somatic mutations. Stratton showed that in non-cancerous colon tissue, almost everyone accumulates ~50 mutations a year throughout their life, which is high among cell types. A deeper dive into the landscape of somatic mutations showed that some mutational signatures and processes are ubiquitous, while others are sporadic; i.e., they will either affect some but not all people, or some but not all cell clones. The results highlight how somatic mutation rates – here caused by DNA repair deficiencies – can lead to cancer, and suggest that measuring mutation rates may aid in clinical management. 

Multi-cancer early detection: opportunity and challenges

Dr. Nickolas Papadopoulos, Sidney Kimmel Comprehensive Cancer Center | Baltimore, Maryland, United States of America

In another plenary session, Dr. Papadopoulos discussed early cancer detection using liquid biopsies. Using the example of immunotherapies, which have a better chance of achieving successful outcomes if they’re given early on, his group highlighted the clinical benefit of early detection to facilitate diagnoses while there’s still opportunity for treatment. Papadopoulos then described the range of biomarkers present in blood (DNA, RNA, proteins, exosomes, methylation, metabolites, etc.) while reiterating that the large number of non-tumor cells presents a challenge, especially for “non-shedding” cancers which are notoriously hard to detect with liquid biopsies. He then described several recent studies making use of combined ctDNA and protein data that showed increased detection rates compared with standard of care, highlighting the clinical benefit of next generation liquid biopsy technologies. 

Liquid biopsies in lung cancer

Dr. Caroline Dive, Cancer Research UK, Manchester Institute | Manchester, United Kingdom

In a talk focused on liquid biopsies in lung cancer, Dr. Dive presented her lab’s work on Small Cell Lung Cancer (SCLC), highlighting the need for biomarkers for response to chemotherapy – despite the heterogeneous pattern of mutations in SCLC, current treatment options are largely homogeneous. Dr. Dive then explained the rationale for her focus on subtype-focused clinical trials in SCLC, which can be defined based on various modalities such as ctDNA, circulating tumor cells (CTCs) and CTC derived patient explants (CDX). She then described how differentially methylated regions (DMRs) in ctDNA can be used to subtype SCLC. Using DMRs, Dive demonstrated the high sensitivity of the classifier she and her team built.

A practice changing study 

Dr. Nicolas Girard, Institute Curie | Paris, France 

CheckMate 816, a phase 3 study, found that neoadjuvant nivolumab plus chemotherapy demonstrated a statistically significant improvement in the primary endpoint of Pathological Complete Response (pCR) versus chemotherapy alone in patients with Stage IB-IIIA NSCLC. In this follow up analysis, the co-primary endpoint of Event Free Survival (EFS) was assessed. Nivolumab plus chemotherapy demonstrated improved EFS versus chemotherapy alone in patients with Stage IB-IIIA NSCLC (HR 0.63, 95%CI 0.43-0.91). Median EFS was 31.6 months and 20.8 months for nivolumab plus chemotherapy and chemotherapy alone, respectively. These findings support this recently FDA approved combination and a new potential standard of care for patients with resectable NSCLC. 

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