Chemo-Immunotherapy Combination Shows Promise Against Pancreatic Cancer in New Study

Penn Medicine researchers have announced that a chemotherapy and immunotherapy combination may help to deal with pancreatic cancer, which is one of the most difficult cancer forms to treat.

CT Image of Pancreatic Cancer

CT Image of Pancreatic Cancer.

This finding was made in a nationwide randomized clinical trial that was led by researchers from Penn’s Perelman School of Medicine. Results from the small trial were present at this year’s meeting of the American Society of Clinical Oncology (ASCO). They have also been published in the journal Nature Medicine.

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“This study suggests there is benefit in combining immunotherapy and chemotherapy in patients with advanced pancreatic cancer and there may be ways to fine-tune treatment choices based on the ‘immune health’ of the patient,” said Dr. Robert H. Vonderheide, the John H. Glick Abramson Cancer Center Professor.

Patients who received immunotherapy (nivolumab) and two chemotherapy drugs (nab-paclitaxel and gemcitabine) showed a 57.7 percent survival rate. This was significantly higher than the average for only chemotherapy.

Treatment difficulty

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent type of pancreatic cancer. It is a very damaging form of cancer that is quite difficult to treat.

The treatment difficulty of PDAC is partly because it is typically diagnosed only when it has reached an advanced stage. People with newly-diagnosed metastatic PDAC often do not live up to a year even with the best chemotherapy treatment. Just around 10 percent of patients with this disorder live up to five years following diagnosis.

Evidence suggests that chemotherapy alone is not adequate to fight PDAC. Also, immunotherapies that have shown positive results against certain cancers have proven largely futile against this form when employed singly.

Preclinical mice studies and a small trial reported by Vonderheide and his colleagues in 2021 showed signs that a combination of chemotherapy and immunotherapy may yield better results.

Read Also: Researchers Unravel the Mystery behind Drug Resistance Seen in Pancreatic Ductal Adenocarcinoma

Promising outcomes

In this new trial, the research team randomly assigned more than 100 metastatic PDAC patients into three groups. Subjects in each group received chemotherapy and any of Nivolumab, Sotigalimab, or a combo anti-PD-1 and pro-CD40 immunotherapy. The researchers wanted to find out whether any of these combination treatments could increase the one-year survival rate higher than the historical rate of 35 percent with chemotherapy alone.

The group that got both chemotherapy and nivolumab, which blocks the immune checkpoint PD-1, showed a 57.7 percent one-year survival rate. The rate for the Sotigalimab (pro-CD40) group was 48.1 percent while it was 41.3 percent for the combo anti-PD-1 and pro-CD40 immunotherapy group.

Only the results from the anti-PD-1 (nivolumab) plus chemo group were statistically significant. Researchers theorized that the patients who got both chemotherapy and combo immunotherapy regimen did not get as good results probably because of over-activation of T cells.

Read Also: Pancreatic Cancer Treatment: Modified T Cells Show Strong Anti-Tumor Properties

The team also identified immune system biomarkers that are linked to improved outcomes of treatments. These factors, which include the amounts of certain immune cells in the blood prior to treatment, can guide doctors in choosing the most fitting treatment for each patient.


Sotigalimab and/or Nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial



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