Pancreatic cancer, a formidable challenge in oncology, saw notable advancements in research and treatment throughout 2024, offering renewed hope for patients. Despite remaining one of the most difficult cancers to treat, with projections indicating it may become the second-leading cause of cancer-related death in the U.S. before 2030, recent progress provides optimism. Key developments include new drug approvals, promising clinical trial results, and a growing emphasis on precision medicine.
Survival Rates and Incidence
In early 2024, the announcement that the five-year relative survival rate for pancreatic cancer had risen to 13% marked a positive trend. While this increase is encouraging, pancreatic cancer still lags behind other major solid tumors like breast, lung, colorectal, and prostate cancer, each of which have approved screening tests. The American Cancer Society estimates that approximately 67,440 people in the U.S. will be diagnosed with pancreatic cancer in 2024, and about 51,980 will succumb to the disease.
New Treatment Approvals
February saw FDA approval of Onivyde (liposomal irinotecan) as part of the NALIRIFOX regimen for first-line therapy in patients with metastatic pancreatic cancer. NALIRIFOX combines Onivyde with 5-fluorouracil (5-FU), leucovorin, and oxaliplatin, providing a new treatment option for newly diagnosed metastatic pancreatic cancer patients. Additionally, two tumor-agnostic drug approvals expanded targeted therapy options.
Enhertu (fam-trastuzumab deruxtecan-nxki) received accelerated approval for HER2-positive solid tumors, relevant to the 1-7% of pancreatic cancers that are HER2-positive. Augtyro (repotrectinib) gained accelerated approval for solid tumors with NTRK gene fusions, a rare occurrence in about 0.5% of pancreatic cancer cases.
In December, Bizengri (zenocutuzumab-zbco) received accelerated approval for advanced pancreatic adenocarcinoma with NRG1 fusions, present in roughly 3% of cases. This approval marks a significant step for precision medicine in pancreatic cancer treatment, targeting NRG1 fusions.
Targeted Therapies and RAS Inhibitors
Targeted therapies are emerging as a crucial approach for pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. Many cancers, including PDAC, are driven by mutations in the RAS family of oncogenes. Over 90% of PDAC patients have tumors with a KRAS mutation. The RASolute 302 trial is evaluating RMC-6236, an investigational drug targeting RAS proteins in their "on" state. This Phase 3 trial represents a significant effort to develop effective RAS inhibitors for pancreatic cancer.
Tumor Treating Fields (TTFields)
In December, results from the PANOVA-3 Phase 3 trial showed that Tumor Treating Fields (TTFields) combined with chemotherapy improved overall survival in unresectable, locally advanced pancreatic cancer. TTFields is a non-invasive therapy using low-intensity alternating electrical fields to disrupt tumor cell division. This approach, already approved for glioblastoma and lung cancer, could become a valuable treatment option for PDAC patients.
Precision Medicine and Biomarker Testing
With the increasing availability of targeted therapies, biomarker testing is crucial for identifying actionable alterations in pancreatic tumors. PanCAN strongly recommends that all patients undergo biomarker testing and genetic testing for inherited mutations soon after diagnosis. Tools like PDACai v2.0, an AI-driven chemo predictor, are being developed to provide oncologists with data-driven insights for selecting effective chemotherapy regimens.
Clinical Trial Innovations
PanCAN's Precision Promise trial, a Bayesian platform trial in metastatic pancreatic adenocarcinoma, demonstrates the potential for adaptive clinical trial designs to accelerate drug development. While the addition of pamrevlumab to chemotherapy did not show a benefit, the trial's innovative design and data-sharing initiatives are valuable for future research.
Challenges and Future Directions
Despite these advancements, pancreatic cancer remains difficult to treat due to its late diagnosis, resistance to therapies, and complex tumor microenvironment. The location of the pancreas makes surgical intervention challenging, and the cancer cells often create a protective cocoon of collagen fibers. Future efforts will focus on refining clinical trial methodologies, expanding the therapeutic pipeline, and enhancing biomarker-driven patient subset investigations.
Market Growth and Optimism
The global pancreatic cancer treatment market is expected to grow at a compound annual growth rate (CAGR) of 12.30% from 2025 to 2030, driven by an aging population, lifestyle-related diseases, and governmental support for early diagnosis and advanced therapies. The progress in diagnostics, such as blood tests that can accurately detect early-stage pancreatic cancer, and the promising results from ongoing clinical trials offer hope for improved outcomes for pancreatic cancer patients.
