A humble yet groundbreaking clinical trial at Memorial Sloan Kettering Cancer Center (MSK) has achieved unprecedented results in the treatment of rectal cancer, marking an incredible milestone in oncology. The trial, which utilized the immunotherapy drug dostarlimab (called Jemperli), demonstrated a 100% remission rate in patients with mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H) rectal cancer. This success has led to the U.S. Food and Drug Administration (FDA) to give the therapy the status of “Breakthrough Therapy Designation” on December 16, 2024, accelerating its path toward broader approval and adoption.
A Paradigm Shift in Rectal Cancer Treatment
The MSK trial represents a revolutionary approach to treating rectal cancer by relying solely on immunotherapy rather than the traditional combination of surgery, radiation, and chemotherapy. These standard treatments, while effective, often cause severe side effects such as infertility, incontinence, and bowel dysfunction. By contrast, dostarlimab spares patients from these debilitating complications while delivering remarkable effectiveness.
Dostarlimab is a checkpoint inhibitor that works by causing the body’s immune system to attack cancer cells. Specifically, it targets tumours with MMRd or MSI-H mutations, which occur in approximately 5-10% of rectal cancer cases. These genetic abnormalities make tumours particularly vulnerable to immunotherapy because they build up mutations that encourage an immune response. However, cancer cells can subdue this response by activating immune checkpoints. Dostarlimab blocks these checkpoints, enabling immune cells to recognize and destroy the tumour.
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Clinical Trial Results: Unprecedented Efficacy
The trial initially began with 18 patients and later grew to 42 participants as of June 2024. All patients had stage 2 or 3 rectal tumours with MMRd mutations. They received intravenous infusions of dostarlimab every three weeks for six months. Remarkably, every patient experienced complete remission, with no evidence of disease detected through imaging, endoscopy, or biopsies. The results were sustained over time; some participants have remained cancer-free for up to four years.
Dr. Andrea Cercek and Dr. Luis Diaz, who led the trial at MSK, showed surprise at the rapid and complete responses watched in their patients. Symptoms such as bleeding and pain disappeared within weeks of starting treatment for many participants. Patients reported feeling “normal” again after just a few sessions of immunotherapy. One notable case is that of Sascha Roth, the first participant in the trial. Initially preparing for weeks of radiation therapy, she was informed by Dr. Cercek that her cancer had disappeared after six months of immunotherapy alone. Roth described her reaction as “stunned and ecstatic,” a sentiment echoed by other patients who avoided invasive treatments.
Broader Implications: Changing Clinical Guidelines
The success of this trial has already begun to reshape clinical practice worldwide. The National Comprehensive Cancer Network (NCCN), which sets treatment guidelines in the U.S., has updated its recommendations to include immunotherapy for MMRd rectal cancer patients. This change has made insurers more likely to cover this innovative approach.
Moreover, the trial’s impact extends beyond medical outcomes – it has improved quality of life for patients in profound ways. For instance, three participants have successfully had children post-treatment, an outcome that would have been nearly impossible with conventional therapies that often cause infertility.
Addressing an Urgent Need
Rectal cancer diagnoses are rising among young adults under 50 years old. This is a worrying trend that highlights the importance of less toxic treatment options like dostarlimab. Additionally, individuals with Lynch syndrome, a hereditary condition linked to higher cancer risk and poorer outcomes with standard therapies, stand to benefit significantly from this breakthrough.
Future Directions: Expanding Applications
Encouraged by these results, MSK researchers are exploring whether this “immunoablative” approach—using immunotherapy to replace surgery and other treatments—could be applied to other cancers with MMRd mutations. Trials are currently happening for gastric, pancreatic, and prostate cancers. Drs. Cercek and Diaz emphasize the importance of genetic testing for all rectal cancer patients to determine their eligibility for immunotherapy trials like this one. They also highlight MSK’s unique expertise in treating young-onset colorectal cancers through its specialized Center for Young Onset Colorectal and Gastrointestinal Cancer.
A Transformative Moment in Oncology
The MSK trial has not only delivered hope but also set a new standard for precision medicine in oncology. By targeting specific genetic vulnerabilities with immunotherapy alone, it has spared patients from severe side effects while achieving unparalleled efficacy. Sascha Roth’s words capture the sentiment shared by many participants: “My whole experience has been like a dream.” As researchers continue to build on this success, dostarlimab may herald a new era where cancer treatment is both effective and compassionate.
Disclaimer: This information is not intended to be a substitute for professional medical advice, diagnosis or treatment and is for information only. Always seek the advice of your physician or another qualified health provider with any questions about your medical condition and/or current medication. Do not disregard professional medical advice or delay seeking advice or treatment because of something you have read here.
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