An experimental drug that enlists the body's immune system to fight cancer has completely cleared tumours in people with a specific type of rectal cancer.
Researchers at Memorial Sloan Kettering Cancer Center in New York and Yale University found a six-month course of a drug called dostarlimab caused all 12 patients' tumours to disappear.
At an average follow-up time of a year, the tumours had not grown back.
The results were "wonderful" but still very much preliminary, said Graham Newstead, a colorectal surgeon and medical director of Bowel Cancer Australia.
"This definitely needs a larger trial because it's fabulous stuff. But we ain't there yet."
Satish Warrier, a colorectal surgeon at Peter MacCallum Cancer Centre, Alfred Health and Epworth Healthcare, agreed.
"It's exciting. We're obviously hoping for our patients to get the best outcome, which is a cure.
The study's results were published in the New England Journal of Medicine.
In an accompanying editorial, University of North Carolina gastrointestinal oncologist Hanna Sanoff said the findings were "cause for great optimism", but the drug would not be able to replace current treatments just yet.
Tailored for a subset of rectal cancers
To be eligible for the study, participants needed to tick a couple of boxes first.
First up, their tumours needed to be stage two or stage three, Dr Newstead said.
"Stage two is a tumour which has grown into the wall, and stage three is through the wall into the adjacent tissues or lymph glands.
"So these were moderately advanced cancers."
Their tumours also had at least one gene mutation that stops cells from finding and fixing DNA damage.
This "DNA mismatch repair deficiency" is seen in about 5 per cent of rectal cancer patients, Dr Warrier said.
They generally don't respond well to radiation therapy and chemotherapy, which means treatment often includes surgery to remove part or all of the rectum.
And this can cause long-term problems.
"[By attaching the colon to the anal canal], you're really asking the colon to serve the rectum's purpose, which I describe as fairly intelligent in that it differentiates solids, liquids and gas — all the things you take for granted," Dr Warrier said.
So the aim of the Memorial Sloan Kettering study was to reduce the need for surgery by shrinking as much of the tumour as possible with the drug treatment.
The drug they used, dostarlimab, was developed by GlaxoSmithKline. It's what's known as a "checkpoint inhibitor" and is a current treatment for mismatch-repair-deficient endometrial cancer.
It's not cheap — each dose costs $US11,000 ($15,500).
But it works by "unmasking" tumours. Cancer cells have a bunch of tricks that let them grow and spread while flying under our immune system's radar.
Dostarlimab latches onto proteins found only on rectal cancer cells, alerting the immune system of a target it needs to attack.
The treatment involved nine intravenous doses spaced three weeks apart. The idea was after six months, any remaining tumours would be treated with chemotherapy, radiation therapy and surgery.
But it didn't come to that. The tumours dwindled, then vanished.
"And that was on all the assessments, like positron emission tomography, MRI, examining their rectum again and doing biopsies for anything left behind in the wall," Dr Newstead said.
And, the researchers wrote, "no cases of progression or recurrence had been reported during follow-up (range, six to 25 months)".
What needs to happen now?
One reason the study's results are "exciting", according to Dr Warrier, is it means patients may be able to avoid not only surgery, but radiation therapy as well.
Alongside the 12 people who'd completed the dostarlimab course, another four were part-way through the treatment regimen by the time the study was written up and published.
This, Dr Newstead said, "is a terribly small sample".
"A trial to give definitive answers requires large numbers of patients, two cohorts, one having the drug or the therapy and the other not, comparing equal numbers of males and females.
"[Plus] a significant number of patients who are stage two and a separate number of patients who are stage three, and comparing them long enough to know that there is no recurrence.
It's important to note that most people with rectal cancer, at least 95 per cent, would still require traditional treatments, Dr Warrier said.
Whether the drug works on other types of rectal cancer, or even in people from diverse communities, isn't known yet either, Dr Sanoff wrote.
That's because the trillions of microbes that line our intestines — our gut microbiome — can affect how well immunotherapy works.
The researchers acknowledge their study is just the beginning, and envision dostarlimab will be trialled in other localised tumours with DNA mismatch deficiency, such as some pancreatic, stomach and prostate cancers.
