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    Experimental cancer drug trial shows ‘proof of principle’ that could help treat other tumors

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    After a small cancer drug study yielded the unprecedented result of 100 percent of participants entering remission, oncologists — and patients — wonder if the approach from the experimental drug trial can apply to other types of cancer.

    The study out of Memorial Sloan Kettering Cancer Center in New York has oncologists excited over the prospect that immunotherapy, the treatment type used in the trial, has increasingly shown effectiveness — without surgery — against tumors with a specific abnormality. All of the trial’s participants had tumors with the abnormality known as mismatch repair (MMR) deficiency, a mutation that occurs in between 5 and 10 percent of rectal cancer cases and is also present in endometrial, bladder, breast and prostate tumors.

    Though the trial was tested in patients whose tumor mutation is present in roughly 4 percent of all cancer cases, the results provide a template for how to tailor immunotherapy drugs to attack specific tumors that, due to their mutation, tend to be more resistant to traditional therapies, according to Julie Gralow, chief medical officer and executive vice president of American Society of Clinical Oncology.

    “That’s the promise of this: It’s really the concept of being able to match a tumor, and the genomics of what’s driving it, with a therapy,” Gralow told The Washington Post on Thursday. “Because we can move this beyond just this subset of rectal cancer.”

    The Sloan Kettering trial, which began in late 2019, took 18 early-stage rectal cancer patients with the same tumor mutation who had no prior treatment and gave them the drug dostarlimab every three weeks for six months. Tumors completely disappeared in all 14 patients who had completed the treatment by the time the study published (four more remain on track with similar results), and none have required follow-up treatment.

    The results mark the first time immunotherapy alone eliminated the need for chemotherapy, radiation or surgery, which can cure patients but leave them with life-altering effects like infertility, bowel and sexual dysfunction or permanent reliance on a colostomy bag.

    The study authors note the earliest patient to complete the trial is more than two years post-treatment, and all patients will be monitored for at least five years to ensure no tumor regrowth or reemergence.

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    Scott Kopetz, a professor of gastrointestinal medical oncology at MD Anderson Cancer Center in Houston, called the study “a solid advancement in the field” and described the way immunotherapy has been used to treat MMR deficient tumors as “absolutely game-changing.”

    “The idea of using immunotherapy in patients that have localized early stage colorectal cancers certainly has been gaining momentum,” he said. The new study “provides recognition that if we can get the immune system properly engaged … we can eradicate” those cancers.

    Even cancers in advanced stages have shown sensitivity to drugs like the one used in the trial. Known as “checkpoint inhibitors,” the drugs block a specific cancer cell protein that can cause the immune system to hold back its cancer-fighting response rather than identify and eradicate the cancer. Once eradicated for a number of years, the cancers rarely return, Kopetz said.

    Data from other research show 70 percent of people with metastatic colorectal tumors treated with immunotherapeutic drugs to be cancer-free five years later, he said, a huge advance in treatment for a terrible disease. Metastatic cancers are even more difficult to treat than tumors that are confined to the rectum or colon.

    Small cancer drug trial sees tumors disappear in 100 percent of patients

    The study does come with caveats. Kopetz and others cautioned that six months is not long enough to know whether the patients will remain permanently cancer-free. These drugs often need to be taken for a year or two before patients can come off them and remain confident that their cancer has been eliminated, he said. Unlike chemotherapy and radiation, however, the drugs are usually well-tolerated during that period.

    Perhaps more importantly, the genetic defect in these patients’ tumors that allows the drugs to be so effective, is much less common in other forms of cancer than in colon and endometrial cancers. So a person with a lung or brain cancer that lacks that defect would have a much lower chance of this kind of cure, Kopetz said.

    David Ryan, the director of clinical oncology at Massachusetts General Hospital, previously told The Post that while the treatment used in the trial could become more widely available, not everyone who can receive the treatment will have access to the specialists who will help monitor patients like the trial participants and intervene if tumors come back.

    “We do worry that if recurrences happen, that they have to be picked up as soon as possible to give people the best chance,” Ryan said.

    Gralow, of ASCO, said the study affirms that the future of cancer treatment is a narrower approach based on cancer type, such as a tailored plan that addresses the specific characteristics of a tumor.

    “I’m excited when you see such a dramatic response,” she said of the trial results. “It gives me hope we can find such a dramatic match for other cancers, too.”



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