People on Rectal Cancer Drug Achieve Complete Remission, Small Study Finds

For a small subset of rectal cancer patients, intravenous drug therapy appears promising and may improve their quality of life compared with standard treatment. But larger trials are needed.

Doctor performing endoscopy on a patient at the hospital
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A very small clinical trial with very positive results raises an important question for some people with rectal cancer: Could treatment with a certain intravenous (IV) drug put them in remission, sparing them from surgery, chemotherapy, and radiation?

In a new "groundbreaking clinical trial," researchers observed a 100% complete response rate among patients with a specific type of rectal cancer after completing the immunotherapy treatment dostarlimab—that means all patients within the trial saw their cancer disappear.

The study, presented Sunday at the annual meeting of the American Society of Clinical Oncology in Chicago, and simultaneously published in the New England Journal of Medicine, provides "what may be an early glimpse of a revolutionary treatment shift," according to an accompanying editorial on the research, authored by Hanna K. Sanoff, MD, MPH, a gastrointestinal medical oncologist and clinical researcher with the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.

"I think it is impressive and promising," Anup Kasi, MD, associate professor at the University of Kansas Cancer Center, who was not involved in the research, told Health. "We're not just talking about shrinkage [of the tumors]; it's a complete response."

But while the results have many health care providers feeling optimistic, much more research on the treatment needs to be done—and, according to Dr. Sanoff, the treatment can't yet replace existing approaches. Here's what to know about the details of the study and what it may mean for the future of rectal cancer treatment.

About the Trial

To date, 18 people with rectal cancer have been enrolled in the phase 2 trial led by clinicians at Memorial Sloan Kettering Cancer Center in New York. Per the report in the New England Journal of Medicine, 12 of those volunteers had completed six months of treatment. That's now 14, according to researchers who presented the updated results at ASCO.

The treatment is a type of drug known as a PD-1 "blockade" or "inhibitor." (PD-1 is a protein on immune cells, also known as T-cells. Drugs that block that protein allow T-cells to kill the cancer.)

People in the trial had "locally advanced" rectal cancer. That means their cancer hadn't metastasized, or spread to other parts of the body.

It's important to note that the trial involved people whose tumors had a specific gene mutation that may lead to cancer. Per the study authors, about 5%–10% of rectal cancers have this mutation, called a "mismatch repair deficiency."

"By that token, 90–95% of patients with rectal cancer will not be affected at all by these results," Georgios Karagkounis, MD, assistant professor of surgery and surgical oncology at the University or Texas Southwestern Medical Center, told Health.

What the Study Found

Trial participants were given the IV medication dorstalimab, sold under the brand name Jemperli by GlaxoSmithKline (GSK). In August 2021, the U.S. Food and Drug Administration expanded use of the PD-1 blocker for adults whose recurrent or advanced solid tumors, including endometrial cancer, have this gene defect, per GSK.

Jemperli's list price (what wholesalers pay before discounts and rebates) is $10,628.61 for a 500-milligram dose, GSK said in an email.

The people in the study received IV dorstalimab every three weeks for six months—a total of nine cycles of treatment. All 14 people experienced complete remission, meaning their tumors were no longer detectable by digital rectal exam, endoscopy, MRI, PET scans, or biopsy, the authors reported. At six months, every patient remained cancer-free. As a result, none have needed additional treatment. Five of the 14 have been in remission for a year, lead study author Andrea Cercek, MD, section head of colorectal cancer at Memorial Sloan Kettering (MSK), told Health in an email. Several others will reach one year of follow-up in the next two months.

No serious adverse events have been reported. The most common side effects were rash, itchy skin, fatigue, and nausea. One person in the trial experienced thyroid problems.

Treating Rectal Cancer

Rectal cancer grows in the tissues of rectum, the last segment of the large intestine before the anus. In 2022, it's estimated that nearly 45,000 people in the U.S. will be diagnosed with rectal cancer, according to the American Cancer Society.

Treatment typically involves a combination of chemo, radiation, and surgery. It can be "grueling," Dr. Sanoff said in the accompanying editorial. Treatment can cause longer-term problems, such as neuropathy (numbness and tingling), bowel and sexual problems, and infertility, noted Dr. Sanoff.

Some people need a colostomy after cancer removal. That procedure diverts their stool into a pouch attached to the abdomen.

Colostomy is often required for rectal cancers that develop lower in the rectum, closer to the anus, said Dr. Karagkounis. So, even when standard treatment for rectal cancer is successful, it can have a "transformative impact" on quality of life.

The serious effects and complications of rectal surgery have fueled interest in finding an organ-sparing treatment. To "have a therapy, like the immunotherapy [in this trial] that can avoid the need for radiation, the need for chemotherapy, and the need for surgery is amazing," said Karagkounis.

A New Approach?

PD-1 blockers are used for treating different types of cancer. They're highly effective as a first-line treatment for people with metastatic colorectal cancer with mismatch-repair deficient tumors, the authors noted.

That led the team at MSK to wonder whether a nonsurgical approach might work for non-metastatic rectal cancer with the same gene defect.

The drug turned out to be "remarkably effective" in the 14 patients who have completed treatment to date, the study authors noted.

"The implications for quality of life are substantial, especially in those where standard treatment would affect childbearing potential," Dr. Cercek said in a press release. "As the incidence of rectal cancer is rising in young adults, this approach can have a major impact."

Hesham Abdullah, GSK's senior vice president and global head of oncology development, told Health in an email that the company is "very encouraged by the data presented at ASCO and what this could mean for patients with locally advanced rectal cancer."

While the study findings are "cause for great optimism," Dr. Sanoff suggests that it's too soon to replace the current treatment approach.

For one thing, complete remission doesn't tell the whole story. Cancer regrowth occurs in 20% to 30% of patients who don't have surgery, Dr. Sanoff noted. What's more, little is known about patients' long-term response: How much time must pass before remission equals cure? And can results from this small, largely white group of patients be generalized across the broader population of rectal cancer patients?

Researchers agree that larger studies are needed to replicate the findings and monitor long-term remission.

Most rectal cancer patients don't have tumors that are mismatch-repair deficient, so "unfortunately, this trial did not change their management," said Dr. Karagkounis. "But for the small fraction who do have this, I think it is very, very encouraging news and has potential to radically change their care."

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