When individuals develop solid tumors in the stomach, esophagus, or rectum, oncologists have established treatment strategies. Yet, these treatments can significantly affect quality of life, leading to outcomes such as stomach and bladder removal, permanent colostomy bags, radiation exposure, infertility from chemotherapy, and lasting bodily harm.
In response, a research team at Memorial Sloan Kettering Cancer Center utilized drugs from GSK to explore a novel approach.
They initiated the study with 103 participants, who represent a small fraction (2-3%) of cancer patients with tumors ideally suited for immunotherapy—drugs designed to bypass obstacles that prevent the immune system from attacking cancer cells.
Notably, clinical trials do not generally expect immunotherapy to replace standard treatments. Researchers, led by Dr. Lewis A. Diaz Jr. and Andrea Cerseck, opted to administer dostarlimab, an immunotherapeutic agent.
The outcomes were unexpected and offered hope for a select group of patients faced with these cancers.
In 49 patients with rectal cancer, tumors vanished and did not return after five years. Among 54 patients with other cancers—including esophageal, liver, endometrial, urinary tract, and prostate cancers—35 experienced total tumor disappearance.
Out of the 103 patients, only five experienced a recurrence of cancer. Three were given three doses of immunotherapy, while one was discontinued after the tumor reappeared in the lymph nodes. Currently, the four patients show no signs of disease, while the fifth received further immunotherapy to reduce the tumor size.
On Sunday, investigators presented their findings at the American Cancer Research Association’s Annual Meeting, with a paper featured in the New England Journal of Medicine.
Dr. Bert Vogelstein, an oncologist at Johns Hopkins in Baltimore, termed the results “groundbreaking.”
The drug development’s early stages were conducted in his lab, where he expressed surprise at the advancements.
“The concept of treating large tumors from various organs without surgery seemed like science fiction 20 or 30 years ago,” he noted. However, he emphasized that these discoveries stemmed from decades of foundational research.
The reason immunotherapy succeeded for these significant tumors lies in their gene incompatible repair mutations, which obstruct the correction of DNA damage. This leads to tumors accumulating abnormal proteins that signal the immune system for destruction. Nevertheless, the tumors deploy a shield to fend off immune attacks, which immunotherapy can stimulate, enabling the immune system to target the tumors effectively.
For patients like those in this study, Dr. Michael Oberman, a gastrointestinal cancer specialist at MD Anderson Cancer Center in Houston, suggests the results point towards immunotherapy as an option free of chemotherapy, radiation, or surgery.
However, obstacles remain. The drug is priced around $11,000 per dose, requiring patients to undergo nine infusions over six months. To qualify for insurance coverage, it needs inclusion in clinical guidelines established by professional organizations.
The drug is approved for treating uterine cancer with mismatch repair mutations and is also listed in clinical guidelines for rectal cancer, based on previous small-scale studies. Yet, Dr. Diaz indicated that other cancer patients may face challenges in taking the medication. Nonetheless, Memorial Sloan Kettering continues to recruit participants for clinical trials, meaning those with eligible tumors can access the drug at no cost.
For some individuals, immunotherapy is life-transforming. Side effects can occur, with the study noting fatigue, rashes, and itching as the most common. Rare side effects included pulmonary infections and encephalitis.
Maureen Sidris, a 71-year-old from Amenia, New York, discovered she had cancer after struggling to eat a burger.
“It wouldn’t go down,” she recounted, realizing there was some blockage. Ultimately, it was identified as a tumor at the junction of her stomach and esophagus.
In 2019, she visited Sloan Kettering, where her surgeon advised that surgery, chemotherapy, and radiation were mandatory and that surgery would be complex.
However, due to her tumor’s mismatch repair mutation, she was able to join a clinical trial. Her first injection occurred on October 14 of that year, and by January, her tumor had disappeared. While Sidris experienced one side effect from the treatment requiring medication to support her kidney function, she considers it worthwhile to avoid the challenging treatments initially suggested.
“It was indeed a journey,” she remarked. However, she reasoned that she had everything to gain and nothing to lose by trying immunotherapy.
“If it didn’t succeed, I still had surgery as a backup,” she concluded.
Source: www.nytimes.com
