Several patients with colorectal cancer have responded remarkably well to a combination of two drugs given prior to surgery, with their tumors withering from the inside out1. This promising result could eventually spare some patients the misery of chemotherapy.
Cancer of the colon or rectum, collectively known as colorectal cancer, is the second most common cause of cancer death in the United States. It is usually treated by using surgery to cut out tumors, followed by a course of chemotherapy to mop up any residual cancer cells.
Even after receiving surgery and 3–6 months of chemotherapy, many patients are still not cured. Furthermore, the side effects of chemotherapy can be highly debilitating, and so researchers are seeking new ways to attack cancer that do not involve chemotherapy.
A promising emerging treatment is immunotherapy in which drugs provide the body’s immune system with a boost to help it attack cancer cells. While it has been effective against some forms of colorectal cancer, it is of little use against a common form that is particularly prevalent at the more advanced stages of cancer progression.
A recent study with two next-generation immunotherapy drugs (botensilimab and balstilimab) had shown some activity against colorectal cancer with metastases (stage IV cancer)—but only if there were no tumors in the liver.
“What was weird was that the combination of drugs worked in patients with colorectal cancer who did not have liver tumors or metastases, but not as well in those with them,” says Pashtoon Kasi, an oncologist and researcher at New York Presbyterian Hospital and Weill Cornell Medicine, New York, USA. “Something about the cancer being in the liver caused it to hide under the immune radar.”
Another shift in thinking is providing a preliminary treatment prior to surgery. “Rather than performing surgery and then giving patients mop-up chemo, the idea is to do treatment before surgery,” explains Kasi. “It’s a huge paradigm shift.”
Kasi and his co-workers decided to see what would happen if they provided the two next-generation immunotherapy drugs to patients with immunotherapy-resistant colorectal cancer before surgery. “We wondered what the effect would be if we used these two drugs in a setting where the cancer might be more conducive to immune therapy,” says Kasi.
The results took them by surprise. In the trial, which initially planned to treat 12 patients, the first two consecutive patients showed rapid and dramatic shrinkage in their tumors. “These patients had big tumors before treatment,” says Kasi, “But they were just left with minute amounts of cancer afterwards.”
The results are published in the journal Oncogene, and the paper topped the list of Readers’ Choice Oncogene papers for 2023.
Several patients had no cancer after surgery. Even in tumors when the immunotherapy drugs did not eradicate all the cancer, they attacked the tumors from their roots, just leaving the stalks protruding into the colon or rectum. This may indicate that more patients could be cured in future.
“Given the pattern of kill and downstaging we saw, this treatment could potentially obviate the need for chemotherapy afterwards,” says Kasi.
In addition to publishing a follow-up study on all 12 patients, the team intends to explore the effect of applying the drugs longer. “We want to see if we can get an even deeper response if we give the drugs longer to brew,” says Kasi. The study reopened in February 2024.
References:
1. Kasi, P. M. et al. Oncogene 42, 3252–3259 (2023). https://www.nature.com/articles/s41388-023-02835-y (doi: 10.1038/s41388-023-02835-y)
2. Kasi, P. M. et al. J. Clin. Oncol. 42, 117 (2024). https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.117 (doi: 10.1200/JCO.2024.42.3_suppl.117)
Dr. Pashtoon Kasi is the director for colorectal cancer research at Weill Cornell Medicine in New York and a practicing oncologist at New York Presbyterian Hospital. He is also the director of liquid biopsy research at Weill Cornell’s Englander Institute for Precision Medicine. He focuses on treating patients with gastrointestinal cancers, using precision medicine and novel drugs in early-phase clinical trials. Kasi has authored over 140 peer-reviewed articles and is a frequent speaker at medical and research conferences. Kasi’s work has been featured in local and national media, including coverage in Forbes and The Wall Street Journal.
