2024 AACR Meeting Update

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The American Association of Cancer Research (AACR) Annual Meeting is the focal point of the cancer research community.

The meeting brings together scientists, clinicians, other healthcare professionals, survivors, patients, and advocates to share advances in the more than 100 diseases we call cancer.

The 2024 AACR conference was held April 5th through 10th in San Diego, California. The reports from pancreatic cancer researchers highlighted novel approaches in a broad range of areas, including earlier detection, clinical trials, and immunotherapy; there were also discovery science presentations that will help scientists uncover the secrets of the basic biology of pancreatic cancer.

Here are just a few of the highlights from this important conference. Let’s Win will cover several of these findings in more detail in the coming months. But for now, be assured: progress in pancreatic cancer, from the bench to the bedside, is a reality.

Cancer Vaccines: Ready for Prime Time?

One important question that was discussed is whether cancer vaccines are ready for prime time? Although vaccines are not ready to be standard of care, the approach may prove to be helpful in certain populations. In fact, three of seven presentations in this session were on pancreatic cancer. The research represents three different strategies and included talks on a peptide-based vaccine, a cell-based vaccine, and a personalized mRNA vaccine. Each of the vaccines are being studied in three different areas: prior to disease onset among high-risk groups, before surgery, and after surgery. All three studies are showing positive results, including positive immune responses in those at risk, shrinkage of tumors prior to surgery, and delaying recurrence after surgery.

Let’s Win published reports on the mRNA vaccine in August and September of 2023. However, new data was presented by surgical oncologist Vinod Balachandran, M.D., of the David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center (New York City). He reported three-year follow-up data from a phase I clinical trial that evaluated the postsurgical use of autogene cevumeran combined with immune checkpoint inhibition and chemotherapy for patients with resectable pancreatic cancer. 

This presentation built upon results reported at last year’s AACR Annual Meeting, which showed that patients who had vaccine-induced immune responses were less likely to experience disease recurrence during the first 18 months of follow-up compared with those who did not experience a response to the vaccine. This year, Balachandran reported that, after a median follow-up of three years, responding patients continued to have significantly longer median recurrence-free survival (not reached) compared with those who did not experience a vaccine-induced immune response (13.4 months).  

He also showed that the treatment led to the expansion of multiple CD8+ T cell clones, which, for most responding patients, persisted in the blood long-term and remained responsive in ex vivo rechallenge experiments.

Update on PRECEDE

Diane Simeone, M.D., director of Moores Cancer Center at UC San Diego Health (California), provided updates on the Pancreatic Early Detection (PRECEDE) Consortium, a platform for risk modeling and early detection of pancreatic adenocarcinoma. The goal is to enroll 10,000 individuals over five years across 100 centers and follow longitudinally for 10 years. The study, which opened May 2020, has enrolled 6,545 individuals to date, and continues to enroll about 150 participants per month. Currently, there are 51 active sites with more to come on board in the coming months.

New Liquid Biopsy Shows Promise for Early Detection

Early detection of pancreatic cancer remains challenging due to the nonspecific symptoms of the disease and because the pancreas is located deep within the abdomen, where it cannot be easily palpated during physical examination. Furthermore, existing biomarkers, such as CA19-9, are not reliable on their own to detect early-stage pancreatic cancer.

Ajay Goel, Ph.D., chair of the Department of Molecular Diagnostics and Experimental Therapeutics at City of Hope Cancer Center, Duarte, California, and colleagues explored the potential of an exosome-based liquid biopsy to detect pancreatic cancer at early stages. Liquid biopsies examine blood or other biological fluids for signs of cancer, such as genetic material or cells shed by tumors.

The researchers developed a novel liquid biopsy approach that analyzed specialized vesicles called exosomes, which are shed by cancerous and healthy cells into blood. The researchers previously tested the performance of their exosome-based liquid biopsy signature in a cohort of 95 individuals from either the United States or Japan, reporting a 98 percent pancreatic cancer detection rate. The latest study sought to evaluate the liquid biopsy in large, prospective cohorts from multiple institutions and countries. The study enrolled individuals from the following locations: Japan (150 with pancreatic cancer; 102 healthy donors); the United States (139 with pancreatic cancer; 193 healthy donors); South Korea (184 with pancreatic cancer; 86 healthy donors); and China (50 with pancreatic cancer; 80 healthy donors).

The liquid biopsy signature was trained on information from the Japanese cohort and validated in the cohorts from the United States, South Korea, and China.

The liquid biopsy approach detected: 93 percent of pancreatic cancers in the U.S. cohort; 91 percent of pancreatic cancers in the South Korean cohort; and 88 percent of pancreatic cancers in the Chinese cohort.

Further, when they combined their signature with the pancreatic cancer marker CA 19-9, the liquid biopsy test accurately detected 97 percent of stage I/II pancreatic cancers in the U.S. cohort. This is significant because stage I pancreatic cancers are confined to the pancreas; some stage II cancers have spread to nearby lymph nodes but have not spread to distant sites.

Chemotherapy and Immunotherapy for Surgically Removable Pancreatic Cancer

In this phase I/II trial, neoadjuvant treatment with modified FOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) plus nivolumab (Opdivo) was associated with favorable rates of surgery with no microscopic tumor on the margins. There was median progression-free survival of 21.9 months and median overall survival of 34.6 months, with longer survival for those who successfully went on to surgery, according to presenter Zev Wainberg, M.D., of the UCLA Health (Los Angeles, California).

The 28 patients in this study received modified FOLFIRINOX plus the PD-1 checkpoint inhibitor nivolumab for three to six months. If, after three months, patients were downstaged to resectable disease, they were eligible for an attempt at surgery to completely remove the tumor, with clean margins. If not, they continued treatment for another three months. Of the 28 patients, 22 underwent surgery, with 21 achieving clean margin surgeries and one that had microscopic tumor presence in the surgical margins. Surgery resulted in two pathologic complete responses, two near complete responses, and 15 partial responses.