A new cancer therapy that targets a "shield" that protects tumors from the immune system has surprised scientists by causing all trial participants to go into complete remission, representing what is claimed to be the first time such success has been found. The therapy prevented participants with advanced rectal cancer from needing chemotherapy, radiotherapy, or surgery to remove large parts of their colon, changing – and possibly saving – their lives.
“I believe this is the first time this has happened in the history of cancer,” said Dr Diaz, author of the paper and Head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center, reports the New York Times.
The results were published in the New England Journal of Medicine.
It seems as though excitement over promising results for novel cancer therapies is as sure as the tide, with various approaches in animal models and early trials suggesting great outcomes. However, cancer is highly individual, so one therapy shrinking tumors of even a small number of participants in trials is often touted a success. For just one drug to cause 18 different patients to go into remission is unheard of.
The drug in question is an anti-PD-1 monoclonal antibody named dostarlimab. PD-1 (programmed death-1) is a protein that forms a complex with PD-L1 (programmed death ligand-1) that is expressed on the outside of tumor cells. It acts as a "shield" from the immune system, telling immune cells that they should not attack the tumor and allowing it to grow uncontrollably. It may sound like a wholly-unhelpful protein, but it prevents T cells from attacking other cells that they shouldn’t. Cancer cells can co-opt PD-1 for nefarious uses, allowing them to fly under the radar of the immune system.
Upon discovering this pathway, immunotherapies that inhibit PD-1 (PD-1 blockades) have been theorized, which would unlock the potential of T cells to recognize and destroy cancer cells.
In a phase 2 trial, a small sample of 16 patients with mismatch-repair deficient colorectal cancer were recruited to take a six-month course involving nine cycles of dostarlimab. Of the 16, 12 had completed the course at the time of writing the paper, while four were still undergoing treatment.
To the surprise of the researchers, all 12 participants showed a 100 percent clinical complete response (the cancer was no longer detectable by an array of tests). After a 12-month follow-up appointment, all 12 patients had no disease recurrence, and all 16 patients were still alive.
No serious adverse effects were reported, but 12 patients did experience an adverse event of some degree, most commonly a rash or fatigue.
The results are encouraging, and while the sample is too small for serious conclusions to be drawn, they do provide a compelling foundation for significantly larger trials in the future. Long-term data still needs to be taken, as the endpoints for this study are not ideal for testing long-term cancer management, and the therapy remains expensive (around $11,000 per dose, according to the New York Times), though not as expensive as many novel cancer therapies.
However, for 12 patients, no more treatments are needed to manage what was originally a damning prognosis, allowing them to return to normal life once more.