It was a
small trial, just 18 rectal cancer patients, every one of whom took the same
drug.
But the results
were astonishing. The cancer vanished in every single patient, undetectable by
physical exam; endoscopy; positron emission tomography, or PET scans; or MRI
scans.
اضافة اعلان
Dr Luis A. Diaz Jr
of
Memorial Sloan Kettering Cancer Center, an author of a paper published
Sunday in the New England Journal of Medicine describing the results, which
were sponsored by drug company GlaxoSmithKline, said he knew of no other study
in which a treatment completely obliterated a cancer in every patient.
“I believe this is
the first time this has happened in the history of cancer,” Diaz said.
Dr Alan P. Venook,
a colorectal cancer specialist at the University of California, San Francisco,
who was not involved with the study, said he also thought this was a first.
A complete
remission in every single patient is “unheard-of,” he said.
They entered the study thinking that, when it was over, they would have to undergo those procedures because no one really expected their tumors to disappear.
These rectal
cancer patients had faced grueling treatments — chemotherapy, radiation, and,
most likely, life-altering surgery that could result in bowel, urinary and
sexual dysfunction. Some would need colostomy bags.
They entered the
study thinking that, when it was over, they would have to undergo those
procedures because no one really expected their tumors to disappear.
But they got a
surprise: No further treatment was necessary.
“There were a lot
of happy tears,” said Dr Andrea Cercek, an oncologist at Memorial Sloan
Kettering Cancer Center and a co-author of the paper, which was presented
Sunday at the annual meeting of the American Society of Clinical Oncology.
Another surprise,
Venook added, was that none of the patients had clinically significant
complications.
On average, one in
five patients have some sort of adverse reaction to drugs like the one the
patients took, dostarlimab, known as checkpoint inhibitors. The medication was
given every three weeks for six months and cost about $11,000 per dose. It
unmasks cancer cells, allowing the immune system to identify and destroy them.
While most adverse
reactions are easily managed, as many as three percent to five percent of patients who
take checkpoint inhibitors have more severe complications that, in some cases,
result in muscle weakness and difficulty swallowing and chewing.
The absence of
significant side effects, Venook said, means that “either they did not treat
enough patients or, somehow, these cancers are just plain different.”
In an editorial
accompanying the paper, Dr Hanna K. Sanoff of the
University of North Carolina’s
Lineberger Comprehensive Cancer Center, who was not involved in the study,
called it “small but compelling.” She added, though, that it is not clear if
the patients are cured.
The inspiration
for the rectal cancer study came from a clinical trial Diaz led in 2017 that
Merck, the drug maker, funded. It involved 86 people with metastatic cancer that
originated in various parts of their bodies. But the cancers all shared a gene
mutation that prevented cells from repairing damage to
DNA. These mutations occur
in 4 percent of all cancer patients.
Patients in that
trial took a Merck checkpoint inhibitor, pembrolizumab, for up to two years.
Tumors shrank or stabilized in about one-third to one-half of the patients, and
they lived longer. Tumors vanished in 10 percent of the trial’s participants.
That led Cercek
and Diaz to ask: What would happen if the drug were used much earlier in the
course of disease, before the cancer had a chance to spread?
They settled on a
study of patients with locally advanced rectal cancer — tumors that had spread
in the rectum and sometimes to the lymph nodes but not to other organs. Cercek
had noticed that chemotherapy was not helping a portion of patients who had the
same mutations that affected the patients in the 2017 trial. Instead of
shrinking during treatment, their rectal tumors grew.
Perhaps, Cercek
and Diaz reasoned, immunotherapy with a checkpoint inhibitor would allow such
patients to avoid chemotherapy, radiation, and surgery.
Diaz began asking
companies that made checkpoint inhibitors if they would sponsor a small trial.
They turned him down, saying the trial was too risky. He and Cercek wanted to
give the drug to patients who could be cured with standard treatments. What the
researchers were proposing might end up allowing the cancers to grow beyond the
point at which they could be cured.
The inspiration for the rectal cancer study came from a clinical trial Diaz led in 2017 that Merck, the drug maker, funded. It involved 86 people with metastatic cancer that originated in various parts of their bodies.
“It is very hard
to alter the standard of care,” Diaz said. “The whole standard-of-care
machinery wants to do the surgery.”
Finally, a small
biotechnology firm, Tesaro, agreed to sponsor the study. Tesaro was bought by
GlaxoSmithKline, and Diaz said he had to remind the larger company that they
were doing the study — company executives had all but forgotten about the small
trial.
Their first
patient was Sascha Roth, then 38. She first noticed some rectal bleeding in
2019 but otherwise felt fine — she is a runner and helps manage a family
furniture store in Bethesda, Maryland.
During a
sigmoidoscopy, she recalled, her gastroenterologist said, “Oh no. I was not
expecting this!”
The next day, the
doctor called Roth. He had had the tumor biopsied. “It’s definitely cancer,” he
told her.
“I completely
melted down,” she said.
Soon, she was
scheduled to start chemotherapy at
Georgetown University, but a friend had
insisted she first see Dr Philip Paty at Memorial Sloan Kettering. Paty told
her he was almost certain her cancer included the mutation that made it
unlikely to respond well to chemotherapy. It turned out, though, that Roth was
eligible to enter the clinical trial. If she had started chemotherapy, she
would not have been.
Not expecting a
complete response to dostarlimab, Roth had planned to move to New York for
radiation, chemotherapy and possibly surgery after the trial ended. To preserve
her fertility after the expected radiation treatment, she had her ovaries
removed and put back under her ribs.
After the trial,
Cercek gave her the news.
“We looked at your
scans,” she said. “There is absolutely no cancer.” She did not need any further
treatment.
“I told my
family,” Roth said. “They didn’t believe me.”
But two years later, she
still does not have a trace of cancer.
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