Fourteen people no longer have stage 2 or 3 rectal cancer because of an experimental use of immunotherapy. Enrolling in a clinical trial has, for the past 25 months and counting, spared them from surgery, chemotherapy, and radiation, which are the standard treatments for colorectal cancer. [1]
Fourteen people may not sound like many, but it was 100% of the participants in the study. Every single one of them now has no evidence of disease. The statistician on the study estimated the likelihood of having 14 consecutive clinical trial participants achieve no evidence of disease in a cancer study as one in a trillion. it is a thrilling start to a new application of an existing therapy. [2]
Dr. Andrea Cercek presented this remarkable news at the 2022 ASCO Annual Meeting in June.[3]
The patients took dostarlimab, an anti-PD-1 monoclonal antibody, every three weeks over a period of six months. (The July 18 Medivizor post describes another breakthrough use of monoclonal antibodies in breast cancer, also announced at the ASCO meeting.)
Dostarlimab is not a unique drug; pembrolizumab is another monoclonal antibody that targets the PD1 protein, marking a cancer cell for destruction by the immune system. PD1 inhibitors are often effective when used in metastasized MMRD/MSI rectal tumors. What was new about this study were both the patient group chosen for this treatment and the time during the disease progression when they were given the treatment.[2][4]
The study was limited to patients with stage 2 or 3 disease who had locally advanced rectal tumors (not patients with metastatic cancer) showing the genetic variants MMRD (mismatched repair deficient) and/or MSI (microsatellite instability). Only about 5% of rectal cancer patients have this variant.
Also, the study tried using immunotherapy as a neoadjuvant treatment – before any surgery.
Targeted immunotherapies are generally used after the disease progresses despite other standard treatments, like surgery, chemotherapy and radiation therapy. The participants in the study were taking a risk by delaying surgery and chemo.
“We moved this therapy from advanced disease into early stage disease, and clearly we are seeing increased sensitivity when the tumors are early stage, when they are in the organ where they begin,” says Dr. Luis Diaz, one of the researchers conducting the trial.[2]
Next Steps
“We need to look at the remaining 95% of colorectal cancers that are not mismatch repair deficient and see if we can take advantage of what we learned here to engage the immune system. We may see responses like this in other tumor types,” says Dr. Diaz. “Our goal is to replicate this in other solid tumors, such as stomach, pancreatic, and bladder tumors that are MMRD where they have this potential sensitivity for immunotherapy.”[2]
The study is ongoing. Diaz notes that “we are investigating if this same method may help other cancers where the treatments are often life-altering and tumors can be MMRD. We are currently enrolling patients with gastric (stomach), prostate, and pancreatic cancers.” The study details are on clinicaltrials.gov, trial number NCT04165772.[5]
Patient Actions
Drs. Diaz and Cercek are being deluged with inquiries about their results. For patients, they suggest that all rectal cancer patients talk to their doctors about being genetically tested for this MMRD variant. “We do have a relatively easy way to test for it. We’ve been instructing patients and their doctors to test your tumor for this marker,” says Diaz.[2]
What about the other 95% of patients who lack the variant? Dr. Diaz wants patients to remember that rectal cancer is curative. A colonoscopy can screen for it. All patients have options. Continue to talk to your doctors about both standard treatment and clinical trials. [2] [6]
References:
[2]https://www.mskcc.org/videos/breakthrough-rectal-cancer-drug-trial-what-it-means
[4]https://www.nejm.org/doi/full/10.1056/NEJMoa2201445
[6]https://my.clevelandclinic.org/health/diseases/21733-rectal-cancer
Image: Original Author: Nick Youngson http://www.nyphotographic.com/
