A pilot study led by UCLC investigators suggests that people with borderline resectable pancreatic cancer may achieve superior outcomes if treated with a neoadjuvant chemotherapy-immunotherapy drug combination.1
About Pancreatic Cancer
There will be approximately 40,000 individuals diagnosed with pancreatic cancer this year, and pancreatic cancer is the fourth leading cause of cancer death in the United States. Treatment for early pancreatic cancer has historically included surgery to remove as much of the cancer as possible followed by the administration of Gemzar, 5-fluorouracil (5-FU) or other chemotherapy drugs with modest benefit. New treatment approaches are clearly needed for this difficult to treat cancer.
Neoadjuvant therapy refers to treatments given before the main treatment, usually surgical resection, to shrink the tumor, eradicate micrometastases of cancer early, and improve the chance of a successful surgery. The rational to use neoadjuvant therapy in pancreatic cancer is important for several reasons:
- Limited Resectability at Diagnosis: Only about 20% of pancreatic ductal adenocarcinoma (PDAC) patients are considered to have a resectable cancer at the time of diagnosis. Neoadjuvant treatment can increase the number of patients who can undergo surgery with curative intent.2
- Borderline Resectable and Locally Advanced Disease: For patients with borderline resectable or locally advanced pancreatic cancer, neoadjuvant therapy has been shown to improve resectability and survival making surgical resection possible for some patients who initially presented with unresectable disease.2,3
- Improvement in Survival Rates: Studies have demonstrated that neoadjuvant therapy can delay cancer recurrence and improve overall survival. It ensures that all patients receive systemic therapy early in their treatment course, which is crucial for controlling micrometastatic disease.2,3
Neoadjuvant chemotherapy treatment for pancreatic cancer may include chemotherapy, chemoradiotherapy, or a combination of both. Common chemotherapy regimens include FOLFIRINOX (a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin) and gemcitabine with nab-paclitaxel.2,3
Immunotherapy
A class of medicines called “checkpoint inhibitors” are the latest advance in managing cancer – a type of immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses and allow cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and kill cancer cells.
In the current clinical study 28 patients with borderline resectable pancreatic cancer were treated with at least three cycles of checkpoint inhibitor immunotherapy combined with chemotherapy prior to undergoing surgery. Treating patients with the combination resulted in a higher rate of successful tumor removal, increased the period of time before the cancer worsened, and extended overall survival when compared to historical controls.
At a median follow-up of 24 months, the average time until cancer progression was 34.8 months, and the average overall survival duration was 35.1 months. For patients who underwent a pancreatectomy, the 18-month overall survival rate was 90%.
The role of neoadjuvant therapy in pancreatic cancer is still being evaluated in ongoing clinical trials. This research opens up new avenues for exploring the role of immunotherapy in earlier stages of pancreatic cancer, potentially offering more effective treatment options for patients with borderline resectable pancreatic cancer.
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