A newly discovered cancer treatment can stop the disease from advancing in patients who are resistant to immunotherapy. 

Immunotherapy is a type of cancer treatment that employs the immune system to target and kill cancer cells. It can save lives when other treatment choices, such as surgery, radiotherapy, or chemotherapy, have failed. Treatment cannot, however, benefit all patients, and some tumors can adapt to resist it.

Oncologists in the United Kingdom have discovered that combining immunotherapy with guadecitabine, a novel investigational medicine, can reverse cancer's resistance to immunotherapy. They discovered that patients who were anticipated to die after exhausted all therapy options lived far longer.

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The combination of immunotherapy medicine pembrolizumab and next-generation DNA hypomethylating agent guadecitabine slowed the progression of cancer in more than a third of patients enrolled in the early phase 1 trial. The findings were published in the Journal for ImmunoTherapy of Cancer.

The combination could become an effective weapon against different forms of cancer, experts revealed at the Institute of Cancer Research and Royal Marsden NHS foundation trust. 

Patients in the trial, from the Royal Marsden and University College London hospital, included those with lung, breast, prostate, and bowel cancer.

Treatment 

The study used pembrolizumab and guadecitabine to treat 34 cancer patients, 30 of whom had their tumors analyzed for immune activity and cancer growth. Every three weeks for three years, they had an injection of guadecitabine for four days in a row – and pembrolizumab on the first of those days.

Pembrolizumab is an immune checkpoint inhibitor drug that has already proved successful in treating a range of cancers, including lung and skin cancers. However, tumors can develop resistance to it and some patients who initially benefit will eventually get sicker.

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The study lead, Anna Minchom, a clinical scientist at the Institute of Cancer Research and a consultant medical oncologist at the Royal Marsden, said: “Immunotherapy has shown amazing promise in cancer care over the last decade, but it doesn’t work well in all cancers and cancers can often become resistant. This combination might be a way to target their cancer even after it has stopped responding to immunotherapy.”

Guadecitabine may help overcome this resistance, doctors, researchers and scientists involved in the trial have discovered.

37% record no tumor progression 

The tumor stopped progressing in 37% of the 30 patients whose cancer activity was studied, during 24 weeks or more. Prior to the experiment, three-fifths of the cohort (60%) were resistant to immunotherapy. Almost four in ten (39%) did not become ill as a result of the drug combination.

The new treatment could help lung cancer patients. Of those resistant to immunotherapy, half had their disease controlled for 24 weeks or more.

A patient from Dorset, Alison Sowden, was diagnosed with lung cancer four years ago and was told she had a year to live, but then received pembrolizumab for three years. She is now free of cancer.

“I know there is a chance that my cancer may come back and develop resistance to treatment, so it is reassuring to know research efforts aiming to reverse cancer’s resistance to immunotherapy are under way,” she said.

“I hope this new experimental drug combination will eventually make it to the clinic and help people who have developed resistance to pembrolizumab.”