Exclusive: UK study reveals drug combinations can treat cancers that have developed resistance to immunotherapy.
In individuals who are resistant to immunotherapy, a novel tumor medication can halt the spread of the disease.
When other treatment options, such as surgery, radiotherapy, or chemotherapy have failed, immunotherapy employs the immune system to target and kill tumor cells and can save lives. However, not all patients will benefit from it, and some tumors may develop resistance to it.
Recently, physicians in the UK discovered that immunotherapy in combination with the innovative experimental medicine guadecitabine can overcome tumor resistance to immunotherapy. They discovered that patients who were predicted to pass away after trying all available treatments lived significantly longer.
In more than a third of the patients enrolled in the early phase 1 trial, the combination of the immunotherapy medicine pembrolizumab and the next-generation DNA hypomethylating agent guadecitabine stopped the progression of the malignancy. The Journal for ImmunoTherapy of tumor publishes the results.
According to specialists at the Institute of Tumor Research and Royal Marsden NHS foundation trust, the dual combination could develop into a potent new weapon against a variety of tumor types.
Lung, breast, prostate, and bowel tumor patients from the Royal Marsden and University College London hospitals participated in the trial.
The experiment’s main investigator, Prof. Johann de Bono, stated, “I think one of the most noteworthy aspects about this trial is that we employed multiple different approaches to check for changes in the immune system, robustly indicating that it was being altered by the combo medication”.
De Bono, a professor of experimental cancer medicine at the Institute of Cancer Research and a consultant medical oncologist at the Royal Marsden, continued, “In the long run, we hope that guadecitabine and pembrolizumab could help to tackle some of the resistance to immunotherapy we see in too many types of tumor if these effects are confirmed in other patient groups and future studies.”
Thirty of the 34 tumor patients in the research had their tumors examined for immune activation and tumor growth while receiving treatment with pembrolizumab and guadecitabine. They received guadecitabine injections four days in a row, every three weeks for three years, along with pembrolizumab on the first of those days.
The immune checkpoint inhibitor medicine pembrolizumab has already shown promise in the treatment of a number of malignancies, including lung and skin cancers. Although some patients initially benefit, some tumors may acquire resistance to treatment, making them eventually sicker.
The study’s principal investigator, Dr. Anna Minchom, a consultant medical oncologist at the Royal Marsden and a clinical scientist at the Institute of Cancer Research, said: “Immunotherapy has shown amazing promise in tumor care over the last decade, but it does not work well in all tumors, and cancers can frequently become resistant to it. Their tumor may still be targeted with this combination even after it has ceased to react to immunotherapy.
The trial’s participating physicians, scientists, and researchers have determined that guadecitabine may aid in overcoming this resistance.
A total of 37% of the 30 individuals whose tumor activity was examined had their malignancy completely halted, with no tumor progressing for 24 weeks or longer. 60% of the group had immunotherapy resistance prior to the trial. Nearly four out of ten (39%) of them did not become ill as a result of taking the medicine combination.
Those with lung cancer appear to benefit most from the new treatment. Half of the immunotherapy-resistant patients had their condition under control for 24 weeks or longer.
When Alison Sowden, 61, of Dorset, was given a year to live after receiving a lung cancer diagnosis four years prior, she instead received pembrolizumab for three years. She no longer has a tumor.
”It gives me comfort to know that research is being done to overcome tumor resistance to immunotherapy because I am aware that there is a possibility that my cancer can recur and become resistant to treatment. I’m hoping that this novel combination of experimental medications will eventually reach the clinic and assist those who have become resistant to pembrolizumab”.
