Current Standards and Emerging Options for Pancreatic Cancer

At the 2023 World Congress on Gastrointestinal Cancers, Eileen O’Reilly, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses the existing standards and upcoming options for the treatment of pancreatic cancer.

Dr O'Reilly reviewed the recent findings from the NAPOLI-3 and FOOTPATH trials, regarding chemotherapy for pancreas cancer, as well as targeted treatments, in particular for KRAS-mutated disease, and the potential of a vaccine targeting KRAS. 

Transcript:

Hello, everyone. I'm Eileen O'Reilly from Memorial Sloan Kettering Cancer Center in New York, here today to summarize the highlights from the 2023 World Congress on GI Cancers meeting in Barcelona, reviewing the current standards and where the field is headed in pancreas cancer. To start the summary, I think it's exciting times in pancreas cancer, we're seeing a lot of interest in drug development in this disease, and some emerging, promising, new targeted approaches that we'll briefly touch upon.

Going initially to the standard approaches, for now, in 2023 cytotoxic chemotherapy remains the mainstay for this disease. We reviewed results from the NAPOLI-3 trial. This was updated from the presentation at the 2023 ASCO Symposium on GI Cancers earlier in the year, reporting on 12- and 18-month survivals, both progression-free, and overall survivals, and confirming that NALIRIFOX was superior to gemcitabine and nab-paclitaxel with regard to progression-free and overall survival, and numerically increased response rates. This addresses definitively the question of a 4-drug combination being superior to gemcitabine and nab-paclitaxel in untreated, advanced disease.

The second point to note, with regard to standard therapies in the frontline advanced pancreas cancer setting, is we saw additional data at the 2023 ASCO Annual Meeting from the FOOTPATH study, which looked at sequencing chemotherapy using the NAPOLI-1 regimen followed by 5-FU-based therapy versus gemcitabine and nab-paclitaxel. And there were some surprising outcomes for that, in that we saw neither the NAPOLI-1 regimen nor the sequenced treatment met progression-free survival superiority relative to gemcitabine and nab-paclitaxel. But the sequential strategy suggested maybe less toxicity.

Moving to targeted treatment. In pancreas cancer we now have a number of targeted opportunities, first in BRCA-related disease, secondly, mismatch repair deficiency, and thirdly, the KRAS wild-type actionable fusion alterations. And these are established, although relatively rare, subsets of patients for which there are targeted opportunities available.

I think the big news in the pancreas cancer world is in the KRAS-mutated space. There has been clear proof of principle with KRAS G12C targeting. We've had 2 different therapeutic agents, sotorasib and adagrasib, indicating benefit in previously-treated KRAS G12C-mutated pancreas cancer. And we're now in the era of G12D and pan-RAS or all-RAS and multi-RAS untargeted approaches which are being evaluated, and we'll look forward at this meeting, hopefully in 2024, and beyond, to discuss some of the updates as those studies begin to mature.

We also reviewed some data on an encouraging vaccine, also targeting KRAS, building on a platform approach which combines a KRAS G12R- and G12D-targeted vaccine, ELI-002P, with a template where it is delivered subcutaneously to lymph nodes and can induce a specific and potent T-cell response in an MRD-positive pancreas cancer and colorectal cancer cohort. We saw that this was safe, we saw that this was feasible. We saw that it induced high magnitude T-cell CD4 and CD8 responses, and that this led to ctDNA and tumor marker clearance in these diseases. This product, and an expanded one which covers 7 common KRAS mutated variants, will be evaluated in a randomized Phase 2 later this year.

These are some of the highlights from the World GI Cancer Symposium 2023. Please stay tuned, a lot happening in pancreas cancer. And thank you for listening today.

Source:

O’Reilly EM. Current Standards & New Emerging Options for Pancreatic Cancer. Presented at 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain.