Two experimental drugs for pancreatic cancer showed significant survival benefits in separate clinical trials, offering latest hope for a disease with historically poor outcomes.
In a Phase 2 trial published in Nature, the combination of elraglusib and gemcitabine plus nab-paclitaxel (GnP) extended median overall survival by 2.9 months compared to GnP alone, with patients living 10.1 months versus 7.2 months. The one-year survival rate was 44.1% in the elraglusib/GnP arm versus 22.3% in the control group.
Meanwhile, Revolution Medicines reported that its Phase 3 trial of daraxonrasib, a daily oral pill targeting RAS mutations, nearly doubled survival for patients whose cancer had progressed after prior treatment. Patients taking daraxonrasib lived a median of 13.2 months compared to 6.7 months on chemotherapy, a 6.5-month improvement and a 60% reduction in death risk.
The elraglusib trial included a higher-risk patient population than typical studies, with over 25% having baseline CA 19-9 levels above 8,000 U/ml and low albumin, factors linked to poor prognosis. Despite this, the GnP control arm showed lower-than-expected survival at 7.2 months, aligning more closely with real-world data than historical trial averages of 8 to 10 months.
Daraxonrasib’s benefit persisted regardless of subsequent therapy, and Revolution Medicines plans to seek FDA approval using a Commissioner’s National Priority Voucher, which could accelerate review to within months. The drug targets RAS mutations, present in about 90% of pancreatic cancers, marking a potential shift from exclusive reliance on cytotoxic chemotherapy.
Dr. Shubham Pant of MD Anderson Cancer Center, who has studied daraxonrasib since its early development, described the results as transformational, noting previous trials had only extended survival by weeks or months. He became emotional discussing patient outcomes, including one individual he had seen shortly before the interview.
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Former Senator Ben Sasse, diagnosed with pancreatic cancer late last year, shared in a New York Times interview that his tumors shrank 76% after starting daraxonrasib under Pant’s care, though he reported significant side effects including a peeling facial rash. Revolution Medicines acknowledged rash as a known, generally manageable adverse effect.
The survival advantage with elraglusib/GnP emerged without a significant improvement in progression-free survival, a pattern seen in immunomodulator therapies where immune-mediated effects may delay tumor response but ultimately prolong life. Researchers suggest this disconnect reflects delayed but sustained clinical benefit from immune activation.
Both trials underscore a critical need in pancreatic cancer treatment: the five-year survival rate remains just 13%, the lowest among major cancers, and most patients face rapid progression after diagnosis.
Elraglusib, a GSK-3 inhibitor, works by modulating immune response rather than directly killing tumor cells, which may explain why survival gains appeared early and persisted after treatment ended, even without corresponding tumor shrinkage metrics.
Revolution Medicines emphasized that daraxonrasib’s efficacy in heavily pretreated patients — whose cancer had already resisted other therapies — makes the survival benefit particularly notable, as this group typically has limited options and poor prognosis.
The company has not disclosed pricing or exact timelines for FDA submission but indicated the National Priority Voucher could shorten the approval process significantly compared to standard review cycles.
How do these drugs differ in their mechanism of action?
Elraglusib is a GSK-3 inhibitor that modulates immune system activity to indirectly fight tumors, while daraxonrasib directly targets mutant RAS proteins that drive uncontrolled cell growth in approximately 90% of pancreatic cancers.
Why might survival improve without a corresponding delay in tumor growth?
In immunotherapy-adjacent treatments like elraglusib, immune-mediated effects can take time to activate, leading to delayed tumor response but sustained long-term survival benefits, a pattern observed in other immune-modulating cancer therapies.