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.
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.
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.
This article was originally published in the Science-Based Medicine Blog.