A recent immunotherapy clinical trial by the Memorial Sloan Kettering Cancer Center (MSK) yielded unprecedented results—remission for every single participant. While it was a small trial with 14 participants, the results are extremely encouraging. According to MSK oncologist Dr. Luis Diaz Jr., this may be the first time in cancer research history that 100 percent of a trial’s participants have shown remission. Let’s look closer at this trial and the implications it could have for immunotherapy.
Can Dostarlimab Effectively Treat Rectal Cancer?
The trial tested an immunotherapy drug called dostarlimab (brand name Jemperli), which is typically used as a treatment for endometrial cancer. However, this was the first clinical trial that investigated whether the drug could be used to treat rectal cancer tumors. The trial tested dostarlimab as the sole treatment method for participants, meaning it was not administered in combination with chemotherapy or radiation.
The early results of this ongoing trial could not have been more successful. Every trial patient showed successful cancer treatment after taking dostarlimab. All participants had tumors with a specific genetic mutation called mismatch repair deficiency (MMRd), which affects between 5 percent and 10 percent of rectal cancer patients.
Patients with MMRd are typically less responsive to chemotherapy and radiation and often require surgery. However, this mutation can also make cancer cells more susceptible to immune response. This effect can be enhanced when MMRd mutations are assisted by immunotherapy agents, such as checkpoint inhibitors like dostarlimab. The checkpoint inhibitor removes restrictions on immune cells, allowing them to attack and kill cancer cells more effectively.
When the mutations accumulate inside of the tumor, they act as a stimulant for the immune system, propelling it to attack cancer cells with the mutation. The MSK researchers decided to test this mechanism as a primary treatment method before the cancer metastasized (or spread to the rest of the body).
Challenges of Standard Cancer Treatments for Rectal Cancer Patients
These findings could provide a much more effective treatment for rectal cancer patients, who typically struggle with the standard treatment options of surgery, chemotherapy, and radiation. However, the location of rectal tumors presents the risk of several lifelong complications caused by these treatments. Rectal cancer patients who undergo these treatments often suffer from bowel and bladder dysfunction, incontinence, infertility, sexual dysfunction, and other life-altering conditions.
The fact that this study showed a 100 percent success rate with the immunotherapy drug alone is extremely promising, as the findings show that dostarlimab could provide a way for rectal cancer patients to avoid the standard treatment methods and these devastating side effects altogether.
Methodology and Results of the Immunotherapy Rectal Cancer Study
Participants in MSK’s phase 2 study were given a dose of dostarlimab every three weeks for six months. The patients planned to go ahead with standard chemotherapy, radiation, and surgery if their tumors returned. However, this never happened.
The researchers followed up with the patients after six months, and all 14 patients showed a clinical complete response to the immunotherapy drug. Researchers found no evidence of tumors during MRI scans, PET scans, endoscopy, biopsy, and other diagnostic tests. Some patients have remained cancer-free for two years.
About 75 percent of the patients have experienced mild to moderate side effects, such as fatigue, nausea, rashes, and itching. However, none have seen regrowth of their tumors.
Future Research
This trial is ongoing, and the researchers will continue to test dostarlimab on additional patients. The trial is expected to include approximately 30 participants. While the results are extremely encouraging, additional research and data must be gathered before oncologists can definitively confirm that dostarlimab can be safely and effectively used in broader groups of rectal cancer patients.
In response to the study, oncologists like Dr. Hanna K. Sanoff of the University of North Carolina at Chapel Hill have suggested that the results should be treated with both optimism and caution. Dr. Sanoff believes that a clinical complete response to the treatment does not necessarily make it a long-term cancer control option. Although checkpoint inhibitors like dostarlimab can be effective for several years, a minority of cancer patients may still see their tumors regrow after undergoing experimental treatments instead of surgery.
In addition to awaiting the full results of the completed MSK trial, further research will need to be conducted to determine if these results can be replicated on a large scale. Researchers still know very little about how much time they need to determine whether a clinical complete response to the immunotherapy drug represents a cure for rectal cancer.
But overall, there is ample reason to be hopeful for the future applications of this research. The MSK researchers have already begun to look into whether this single immunotherapy approach could be effective in patients with other types of cancers that have MMRd, such as certain types of stomach, prostate, and pancreatic cancer.