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ESMO GI 2025 | Second-line treatment decisions in advanced pancreatic cancer
Benjamin Adam Weinberg, MD, Georgetown University, Washington, DC, discusses second-line treatment options for patients with progressive pancreatic cancer who cannot tolerate frontline chemotherapy. The standard approach involves switching between FOLFIRINOX/NALIRIFOX and gemcitabine-nabpaclitaxel regimens. While promising targeted therapies like KRAS inhibitors and treatments for specific biomarkers (MTAP deletion, NRG1 fusions, BRAF mutations) are emerging, most patients still rely on standard second-line chemotherapy. Research continues to explore making immunotherapy effective for this historically immune-resistant tumor. This interview took place at the European Society for Medical Oncology (ESMO) Gastrointestinal Cancer 2025 Congress in Barcelona, Spain.
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Transcript
So for patients who have a progressive become intolerant to frontline chemotherapy which is typically a FOLFORINOX or NALIRIFOX or gemcitabine nabpaclitaxel regimen we typically go with the converse. So if they receive gemcitabine nabpaclitaxel in the first line setting they’re typically getting either FOLFORINOX or NALIRIFOX or they’re typically getting gemcitabine, nabpaclitaxel in the second line setting, outside of folks who have specifically active biomarkers...
So for patients who have a progressive become intolerant to frontline chemotherapy which is typically a FOLFORINOX or NALIRIFOX or gemcitabine nabpaclitaxel regimen we typically go with the converse. So if they receive gemcitabine nabpaclitaxel in the first line setting they’re typically getting either FOLFORINOX or NALIRIFOX or they’re typically getting gemcitabine, nabpaclitaxel in the second line setting, outside of folks who have specifically active biomarkers. So obviously there’s been a revolution in KRAS targeting, not yet approved, but we hope in the newer future to have approved KRAS inhibitors in the second line setting. Again, if we can find things like MTAP deletion, we published recently NRG1 fusions with zenocutuzumab, especially for the KRAS wild type group. We also see, you know, rarely things like BRAF, V600E mutations, and a variety of rare but potentially actionable target mutations. But unfortunately, we’re still stuck mostly with our standard second-line chemo, which is why we’re doing studies like this to try to make immunotherapy work for a tumor that’s been historically immune-cold and resistant to immunotherapy.
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