For the very first time, a groundbreaking immunotherapy drug has achieved a remarkable 100% remission rate for a specific variant of rectal cancer. This remarkable research involving a group of 12 patients, spearheaded by the distinguished Memorial Sloan Kettering Cancer Center (MSKCC), captivated audiences worldwide, capturing the attention of both cancer patients and curious onlookers in Colorectal Cancer Drug Trial. (Interestingly, in my nearly two decades of experience in the medical field, this was the first study that prompted an excited call from my mother!)
The results of the Colorectal Cancer Drug Trial were truly unprecedented: The PD-1 blockade drug known as dostarlimab, classified as immunotherapy, demonstrated its potential to induce remission as a standalone therapy for the 5-10% of patients whose rectal tumors are categorized as mismatch repair (MMR) deficient – a condition where their DNA cannot correct certain cellular mutations.
While further comprehensive research is essential to establish whether dostarlimab can serve as a long-term cure, the initial data hold both impressive and timely implications.
Colorectal cancer, excluding skin cancer, ranks as the third most prevalent cancer diagnosis in the United States. Alarmingly, there has been a rising incidence of colorectal cancer diagnoses among younger patients. (To clarify, colon cancer originates in the colon, while rectal cancer begins in the rectum – the umbrella term “colorectal cancer” encompasses both types.)
Despite a decline in cases of rectal cancer among older individuals, current trends predict an astonishing 124.2% increase in cases among patients aged 20-34 and a 46% rise among those aged 35-49 by the year 2030. In Dallas, an estimated 30-40% of patients at the Harold C. Simmons Comprehensive Cancer Center are already under the age of 50.
While modern surgical techniques have enabled the preservation of quality of life and bowel function through partial colon removal, rectal cancer surgery often leads to substantial changes in bowel function, occasionally necessitating a permanent colostomy bag for the collection and disposal of fecal matter.
Particularly for younger patients, offering effective non-surgical treatment alternatives can significantly enhance their quality of life, extending potentially up to 50 years or more following a Colorectal Cancer Drug Trial. The recent trial represents the latest stride in a series of revolutionary studies that are propelling us toward the eradication of rectal tumors.
A decade of advancement in rectal cancer care
A decade ago, the treatment of rectal cancer involved radiation and/or chemotherapy to shrink tumors and eliminate rogue cancer cells. Subsequently, patients would undergo surgery to remove the rectum, and possibly the anus, aiming to eradicate the cancer and minimize the risk of recurrence, often followed by supplementary chemotherapy.
Under this approach, around 20% of patients exhibited no traces of cancer in the removed tissue post-surgery. This statistic indicated that radiation and chemotherapy effectively eliminated cancer in one out of five patients who still had to undergo life-altering rectal cancer surgery. This prompted questions regarding the necessity of surgery in these cases. However, the safety of avoiding surgery for select rectal cancer patients remained uncertain.
Observing that certain Colorectal Cancer Drug Trial for patients exhibited no remaining tumors following initial treatments (radiation and/or chemotherapy), a handful of cancer centers (primarily outside the U.S.) allowed patients to defer surgery and opt for surveillance if their tumors became undetectable. Surgery would still be advised if the tumor resurfaced later on. This approach, known as non-operative management or “Watch and Wait,” gained traction with the help of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial led by MSKCC in 2015. Recently, the OPRA trial results indicated that almost half of the patients initially treated with chemotherapy and radiation could forego surgery, and approximately three out of four patients remained in remission three years after treatment initiation. These findings assuaged concerns surrounding the safety of Watch and Wait, contributing to its wider adoption in the U.S.
The noteworthy Colorectal Cancer Drug Trial that attracted attention in June 2022 utilized dostarlimab, an immunotherapy drug, as the primary treatment (before radiation or chemotherapy) for a specific subset of rectal cancer known as mismatch repair (MMR) deficient rectal cancer, representing about 5-10% of rectal cancer cases. Participants in the study had stage 2 or 3 MMR deficient rectal cancer (termed “locally advanced,” meaning it had not spread beyond the rectum and nearby lymph nodes).
Targeting microscopic rectal tumor eradication
MMR-deficient tumors lack one of four critical genes responsible for DNA repair. As cells divide throughout our lives, minor errors occur and are rectified by specialized enzymes – a group known as mismatch repair proteins. In MMR-deficient tumor cells, one of these enzymes is absent due to inheritance or random genetic mutation. This absence of enzymes leads to the accumulation of DNA errors, gradually setting these tumor cells apart from the body’s “normal” cells. This differentiation allows the immune system to identify them as abnormal and initiate an attack.
Many cancer cells, however, carry a protein called PD-L1 on their surface, which connects with the immune system’s T-cells and effectively “tricks” them into deactivating the immune response. This ploy enables the cancer to continue spreading.
Over the last decade, immunotherapy drugs have been developed to target these proteins, bolstering the immune system’s response. Dostarlimab, the focus of the recent study, impedes the bonding of PD-1 on the T-cell with PD-L1 on the cancer cell, preventing cancer from concealing itself and allowing the immune system to mount an attack against the tumor.
The researchers at MSKCC reported an unexpected and remarkable outcome: Dostarlimab alone eradicated tumors in all 12 participants and triggered remission – without the need for planned radiation or chemotherapy, and none of the participants required surgery.
This outcome was both surprising. Although further research is warranted, there is potential for dostarlimab to serve as an effective non-operative treatment option for 5-10% of patients with MMR deficient rectal cancer. However, more time and research are necessary. At UT Southwestern, we are at the forefront of pioneering non-operative treatments for rectal cancer of Colorectal Cancer Drug Trial.
Exploring novel approaches to rectal cancer treatment
Dr. Todd Aguilera, a clinical researcher at UT Southwestern, is enrolling patients in a clinical study focusing on an antiCD40 antagonist immunotherapy for stage 2 and 3 rectal cancers. The trial, named INNATE (Immunotherapy During Neoadjuvant Therapy for Rectal Cancer), is open to patients with both MMR deficient and MMR proficient tumors – the latter accounting for the remaining 90-95% of rectal cancer cases. To learn about eligibility criteria, visit the trial’s information page.
Radiation oncologist Dr. Nina Sanford is also recruiting patients for a Phase I Trial of Dose-Escalated Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR) for Locally Advanced Rectal Cancer. PULSAR has shown impressive efficacy for various cancers that are either inoperable or necessitate life-altering surgeries, such as lung cancer. The study aims to assess whether radiation dosage for rectal cancer patients can be increased without exacerbating toxicity by extending the interval between doses. Detailed eligibility information for the PULSAR trial is available.
Simmons Cancer Center recently received a three-year accreditation from the National Accreditation Program for Rectal Cancer (NAPRC) following a rigorous evaluation. As an academic medical center, UT Southwestern integrates cutting-edge research into our patients’ care plans. Our multidisciplinary cancer teams strike a balance between aggressive strategies and evidence-based approaches, ensuring personalized and safe treatment.
Hence, when promising findings emerge, our experts promptly engage in discussions about the incorporation of novel therapies into our patients’ care regimens. As the sole NCI-designated comprehensive cancer center in North Texas, the Simmons Cancer Center takes it upon itself to establish guidelines that elucidate eligibility criteria for these groundbreaking therapies. These guidelines also shed light on the extent to which these innovative treatments can be beneficial, along with any associated risks.
While the initial outcomes of the present trial are truly remarkable, patients need to realize that long-term results are still unknown – there’s no certainty that patients will be exempt from future radiation, chemotherapy, or surgery. Dostarlimab is currently awaiting FDA approval for non-metastatic rectal cancer. At this time, the drug’s consideration depends on individual cases and is subject to insurance approval.
For eligible patients, immunotherapy offers a potent treatment avenue. However, patients who opt for immunotherapy should seek care at a facility equipped to manage rare but serious complications, including extreme immune responses.
A decade ago, the idea of non-operative management for rectal cancer was scarcely imaginable. Today, it stands as a reality for numerous patients. Remarkable studies like these propel us closer to a future where most if not all, rectal cancer patients can access non-surgical curative treatments.
Q. What is the significance of the Colorectal Cancer Drug Trial?
Ans- The Colorectal Cancer Drug Trial’s significance lies in its potential to revolutionize treatment. By showcasing dostarlimab’s success in inducing remission without surgery for Mismatch Repair Deficiency tumors, it opens doors to non-operative options. This trial offers hope for tailored therapies, reduced side effects, and improved outcomes in rectal cancer care.
Q. How does immunotherapy impact colorectal cancer treatment?
Ans-Immunotherapy transforms colorectal cancer treatment by harnessing the immune system’s power. Drugs like dostarlimab target specific cancer cells, unleashing the immune response against tumors. This approach offers precision treatment, reduced harm to healthy cells, and the potential for lasting remission in patients with colorectal cancer.
Q. What role does Mismatch Repair Deficiency play in cancer development?
Ans-Mismatch Repair Deficiency (MMR) fuels cancer growth. MMR genes fix DNA errors, but mutations lead to faulty repair. Accumulated mutations cause cells to differ from healthy ones, triggering immune response evasion. In colorectal cancer, MMR deficiency drives tumor formation and progression, highlighting its pivotal role in cancer development.
Q. Is Dostarlimab the only immunotherapy drug being studied for rectal cancer?
Ans-No, Dostarlimab is not the sole immunotherapy under scrutiny for rectal cancer. Ongoing research explores diverse immunotherapies like antiCD40 antagonists. These trials investigate novel approaches to harness the immune system against rectal cancer, signaling a promising era of varied treatment options beyond Dostarlimab.
Q. How do non-operative treatment options benefit rectal cancer patients?
Ans-Non-operative treatments offer rectal cancer patients alternatives to surgery. For younger patients, these options preserve bowel function and quality of life. Trials like OPRA emphasize non-operative management’s success, reducing surgery-related complications. These approaches signify a transformative shift, potentially sparing patients from invasive procedures while ensuring effective cancer care.https://en.wikipedia.org/wiki/Colorectal_cancer