This summer, findings were published from a small clinical trial in which every rectal cancer patient who received an immunotherapy treatment went into remission. It made lots of headlines that asked the age-old question: can we cure cancer?
In general, most patients with a deep rectal cancer, or that which has spread to the lymph nodes, receive a combination of chemotherapy and radiation prior to surgery. Even with the most potent chemotherapy regimens and radiation schedules, the chances of no cancer being present before surgery is about 27 percent.
However, in this study, patients who had stage II or III rectal cancer and had a specific DNA change, referred to as mismatch repair deficiency, were given six months of immunotherapy with Dostarlimab. After treatment was completed, there was no cancer left in 100 percent of these patients. This may allow these patients to forgo a surgical resection and preserve their rectum. We connected with two oncologists with the Bon Secours Cancer Institute, Michael Batalo, MD, (pictured above, left) and Rachna Raman, MD, (pictured above, right) to help us break down immunotherapy, these trial results and what this may mean for the future of cancer care.
What is immunotherapy and how did it apply in this study?
Dr. Batalo: Modern immunotherapy, or checkpoint inhibitors, can fight cancer in multiple ways. However, we are still learning about these complex mechanisms and how better to identify which patients may respond best.
One mechanism works by reactivating our immune system to eliminate cancer cells that otherwise weaken our defense’s anti-tumor effects through the PD-L1 pathway. In general, we currently test for three main biomarkers: PD-L1 expression, microsatellite instability (related to mismatch repair deficiency) and tumor mutation burden to see which patients may be eligible for FDA-approved immunotherapy.
This study focused on patients identified to have mismatch repair deficiency that can result from an inherited cancer syndrome or a specific mutation that develops sporadically in the cancer cells. This mismatch repair deficiency can lead to a high number of tumor mutations in the cancer cells. When a high tumor mutation burden is present, it may help the immune system attack the cancer as more of an invader rather than misidentify the cancer as self.
What do the impressive findings of this study mean?
Dr. Raman: This, in my opinion, is certainly a groundbreaking result. But while this is a promising study, it is not practice-changing yet. Due to the small number of patients treated and short follow up, it does not give us a definitive answer on whether this treatment also help our patients live longer.
Dr. Batalo: More studies are needed to determine if these complete responses will translate into a decreased chance of the disease recurring distantly to other sites in the body and if it ultimately improves overall survival for rectal cancer patients with mismatch repair deficiency.
Does Bon Secours have immunotherapy treatment options for cancer patients?
Dr. Raman: Outside of clinical trials, we routinely offer immunotherapy only for patients who have rectal cancer that has metastasized to another organ (Stage IV) and has the specific DNA change of mismatch repair deficiency.
What does this mean for the future of cancer treatment?
Dr. Raman: This is certainly a study which may eventually change our current day practice for rectal cancers, or for other tumors with mismatch repair deficiency where organ preservation is desirable.
Patients with this DNA change should be encouraged to seek enrollment on clinical trials that administer immunotherapy before surgery. Long-term follow-up will allow us to better define the role of immunotherapy in locally advanced rectal cancer.
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