The results of a Clinical Trial for rectal cancer patients published last week in the New England Journal of Medicine contained an extremely unexpected result: a 100% success rate. It’s hard to describe the rarity of any Clinical Trial yielding responses from every participant. The astounding results of this study have quickly circulated through both lay and scientific circles. Indeed, in just one week, the Altmetric (a measure of how much online activity a scholarly article has generated) has already surpassed 7,000. So, why all the buzz about this Trial? Let’s break down the study and results to see what we’ve learned.
The American Cancer Society estimates over 40,000 new cases of rectal cancer in the US in 2022. The standard treatment for locally advanced rectal cancer involves neoadjuvant therapy. Neoadjuvant treatment entails providing a patient with initial therapy, such as chemotherapy, radiation, or both (known as chemoradiation), with the goal of shrinking a tumor to make it easier to remove surgically.
Rectal cancer develops in the rectum, and because the rectum begins at the end of the colon, colon and rectal cancers are often grouped together as colorectal cancer. Cancer can develop through mutations in the genes that correct mistakes made during DNA replication. Knowing a patient’s cancer has this type of mutation, known as a mismatch repair-deficient cancer, can help doctors determine a treatment regimen. Previous work has identified that mismatch repair-deficient colorectal cancer responds to programmed death 1 (PD-1) blockade, a type of immunotherapy. The similarities between colon and rectal cancers led researchers to wonder if mismatch repair-deficient rectal cancer would respond to PD-1 targeting approaches.
To address this question, the research team initiated a phase 2 study to treat mismatch repair-deficient rectal cancer patients with an anti-PD-1 drug called dostarlimab. Patients received dostarlimab every three weeks for six months, and the Clinical Trial protocol intended to treat patients with standard chemoradiation and surgery following the six-month dostarlimab treatment.
The study’s results, published June 5, 2022, included 12 patients who had completed the treatment regimen with six months of follow-up. All 12 patients demonstrated a complete response and exhibited no evidence of tumor! Notably, the researchers used five screening techniques, including digital rectal examination, biopsy, and magnetic resonance imaging (MRI), to look for evidence of cancer. At the time of publication, no patients had required the standard chemoradiotherapy or surgery because all remained tumor-free. The 12 patients’ follow-up times differed, ranging from 6 to 25 months. So, while some patients just completed dostarlimab treatment, others remained in remission for two years.
The study concludes that PD-1 blockade successfully treated mismatch repair-deficient rectal cancer. In addition, it is also notable that patients in the study exhibited minimal adverse events. The authors note that additional follow-up time will establish the durability of the response.