An experimental cancer drug made 100% of rectal cancers disappear in a small trial, allowing subjects to avoid the standard treatment of chemotherapy and surgery . “Some scientists say these kinds of results have never been seen in the history of cancer research.” 100% is hard to believe; the 95% confidence interval was 74 to 100. Whatever the true percentage, if this study is confirmed, it may represent a real game-changer, a revolution in cancer therapy at least for some patients.

Standard treatment

Locally advanced rectal cancer is typically managed with a combination of adjuvant chemotherapy and radiation followed by surgery. Only a quarter of patients have a complete response, and the side effects and complications can be devastating. A substantial percentage of patients develop bowel, urinary, and sexual dysfunction; infertility; and altered quality of life. Resection of the rectum often involves a permanent colostomy. Some patients have been unable to leave home for decades because of fecal incontinence and shame. A non-surgical treatment would be life-altering for these patients. The new trial appears to show that 100% of them can be cured without surgery. 

Mismatch repair deficiency

Up to 10% of rectal adenocarcinomas are mismatch-repair deficient and respond poorly to standard treatment regimens. They have mutations in genes that would normally correct mistakes made when DNA is copied in a cell. Immune checkpoint blockade has been shown to be a highly effective first-line treatment for cancers with mismatch repair deficiency. On the basis of benefits seen in metastatic disease, the authors of the new study hypothesized that single-agent programmed death1 (PD-1) blockade might be beneficial for patients with mismatch-repair-deficient locally advanced rectal cancer. They found that it was beneficial beyond their wildest dreams.

Study design and results

This was a small study published in The New England Journal of Medicine on June 23, 2022; the planned enrollment was 30 patients, but only 12 patients had completed the protocol at the time of publication. It was a small prospective single-group phase 2 study. Dostarlimab (brand name Jemperli) is a monoclonal antibody that was granted accelerated approval in April, 2021 for adults with mismatch repair deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

Subjects were given IV doses of 500 mg dostarlimab every 3 weeks for 6 months. The plan was to follow this with radiation, chemotherapy, and surgery; but patients who had a complete clinical response did not require further treatment. Only a complete clinical response could be evaluated; evaluation of a complete pathological response was impossible without surgery. All of the subjects in the trial had a complete clinical response. There was no recurrence of disease during a median follow-up time of 12 months; surveillance is ongoing. Adverse events were common, but none were serious events classified as grade 3 or higher. Therapeutic responses were rapid; symptoms resolved within 9 weeks in 81% of patients.

Before treatment

After treatment

It’s not cheap

The price of one dose is over $11,000. Still, considering the savings in human suffering and the financial costs of standard treatment, it might turn out to be a bargain.

Conclusion: very encouraging but will require more study 

I still find it hard to believe the reported cure rate of 100%. But I am cautiously optimistic and look forward to further studies. This is a new non-operative approach to treatment of a subgroup of rectal cancer patients, and it might be applicable to as many as 4-5% of all cancer patients. It may represent a real revolution in cancer treatment.

 

Author

  • Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. She received her BA and MD from the University of Washington, did her internship in the Air Force (the second female ever to do so),  and was the first female graduate of the Air Force family practice residency at Eglin Air Force Base. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS (Director of Base Medical Services) and did everything from delivering babies to taking the controls of a B-52. She retired with the rank of Colonel.  In 2008 she published her memoirs, Women Aren't Supposed to Fly.

Posted by Harriet Hall

Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. She received her BA and MD from the University of Washington, did her internship in the Air Force (the second female ever to do so),  and was the first female graduate of the Air Force family practice residency at Eglin Air Force Base. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS (Director of Base Medical Services) and did everything from delivering babies to taking the controls of a B-52. She retired with the rank of Colonel.  In 2008 she published her memoirs, Women Aren't Supposed to Fly.