Small drug study shows 100% remission rate for certain rectal cancers

June 13, 2022
by Thomas Dworetzky, Contributing Reporter
A small monoclonal antibody drug trail involving just a handful — about 18 — rectal cancer patients has had remarkable results.

The rectal cancer tumors in all patients who completed the study became undetectable on physical exam, with endoscopy, PET or MR scans. All have remained cancer-free for long as 2 years, according to a recent study reported in the New England Journal of Medicine.

“I believe this is the first time this has happened in the history of cancer,” Memorial Sloan Kettering Cancer Center's Dr. Luis A. Diaz Jr., one of the paper's authors, told the New York Times.

The results were “unprecedented,” stated NBC News medical contributor Dr. Natalie Azar on TODAY, adding “That’s 100% of patients. We never, ever say that about cancer treatments.”

The paper was presented at the recent annual meeting of the American Society of Clinical Oncology.

The patients who took part in the study were a subset of those with rectal cancer.

This subset, Diaz explained in a Memorial Sloan Kettering release about the study, “have tumors with a specific genetic makeup known as mismatch repair-deficient (MMRd) or microsatellite instability (MSI).”

Roughly 5% to 10% of all rectal cancer patients are estimated to have such MMRd tumors, out of the 45,000 Americans diagnosed a year with rectal cancer.

“An MMRd tumor develops a defect in its ability to repair certain types of mutations that occur in cells,” according to Diaz.

While the immune system would normally discover and destroy such cancerous growth, the tumor can “trip up” the immune cells' checkpoint safeguard, which keeps them from attacking normal cells — thus letting the cancer tumors hide and grow, Diaz explained.

The checkpoint inhibitor drug used in the study, dostarlimab, is an anti–PD-1 monoclonal antibody. The drug “unmasks cancer cells,” noted the Times, which then lets the immune system see and kill them.

Dostarlimab, a GlaxoSmithKline product with the brand name of Jemperli, gained FDA accelerated approval in April 2021 for the treatment of endometrial cancer in adults, according to the agency.

The agent was given every 3 weeks for 6 months to patients, who had mismatch repair–deficient stage II or III rectal adenocarcinoma, according to the researchers. The per dose cost is $11,000.

“Treatment for stage II and III rectal adenocarcinomas [which are locally advanced but have not yet metastasized] now routinely includes surgery, radiation therapy, and chemotherapy. The results of recent phase 3 trials have led to an increase in the intensity of treatment to include multiagent chemotherapy in addition to radiation therapy before proctectomy is performed; such treatment has resulted in a 3-year disease-free survival rate as high as 77%. Unfortunately, this treatment approach is grueling and can cause substantial long-term sequelae, including neuropathy, infertility, and bowel and sexual dysfunction,” Dr. Hanna K. Sanoff noted in an editorial in the NEJM that accompanied the study's publication.

While such checkpoint inhibitors can cause adverse reactions in about 20% of patients, severe problems, including muscle weakness and problems swallowing, impact 3%-5%.

In the editorial, Sanoff, of the University of North Carolina’s Lineberger Comprehensive Cancer Center, noted that the study was “small but compelling,” but cautioned that the patients need to be followed to see if they remain cancer-free.

“Very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” Sanoff advised.