Neoadjuvant PD-1 blockade in early-stage mismatch repair–deficient solid rectal and non-rectal tumors can eliminate the need for surgery in some patients.
Neoadjuvant treatment with a programmed cell death 1 inhibitor induces clinical complete response and leads to organ preservation in a high proportion of patients with early-stage, mismatch repair–deficient solid tumors — regardless of tumor type, new data from a phase 2 study showed.
led to nonoperative management in 80% of patients with stages I-III MMRd rectal and non-rectal tumors. And in all patients who had a clinical complete response, organs were preserved without additional therapy.Early-stage solid tumors are treated in the curative setting with a combination of chemotherapy, radiation, and surgery, which can have “life-changing” negative effects on the quality of life of these patients in survivorship, said lead author Andrea Cercek, MD, with Memorial Sloan Kettering Cancer Center in New York City. “These findings are very important for patients with early-stage MMRd tumors because it’s likely they do not need surgery or radiation if they are treated first with immunotherapy for a sufficient amount of time,” Cercek added.Across the board, roughly 2%-3% of all solid tumors are MMRd, although it is more common in certain tumors, such as Metastatic MMRd tumors are sensitive to immune checkpoint blockade with a single-agent anti–PD-1 therapy and combination PD-1/cytotoxic T-lymphocyte–associated protein 4 therapy.from the current trial showed that PD-1 blockade with dostarlimab alone led to clinical complete responses in 100% of MMRd early-stage rectal cancers. “Given that exciting data and the durability of these responses in the rectal group, we really wanted to ask the question — could nonoperative management of MMRd tumors extend beyond rectal cancer?” Cercek said. The researchers expanded the trial to include 117 patients with MMRd locally advanced solid tumors. At data cutoff, 14 were still receiving treatment with dostarlimab and 103 had completed treatment, including 49 with rectal cancer and 54 with non-rectal solid tumors, which included esophageal, gastric, hepatobiliary, genital, urinary, colon, and gynecologic endometrial cancers. Patients with a complete response to 6 months of neoadjuvant dostarlimab could elect to proceed with nonoperative management, while those with residual disease would proceed with surgery. Among all 103 patients who completed treatment, 84 had a clinical complete response and 82 did not have surgery. All 49 patients with rectal cancer had a complete clinical response and chose nonoperative management; 37 of these patients had a sustained clinical complete response at 12 months, which met the study’s criterion for efficacy. Among the 54 patients with MMRd non-rectal solid tumors who completed dostarlimab treatment, 35 had a clinical complete response and 33 chose to skip surgery. Complete response rates were seen in 100% of urothelial tumors and 82% of colon cancers. The most common tumor types without a complete clinical response were prostate and gastroesophageal tumors. Cercek noted that complete clinical responses were durable. Recurrences were rare and subsequently responded to rechallenge with PD-1 blockade. Circulating tumor DNA was a “reliable liquid biopsy and marker of response and recurrence,” Cercek said. For the rectal cohort, the median follow-up was 30.2 months, and the 2-year recurrence-free survival rate was 96%. In the non-rectal solid tumor cohort, the median follow-up was shorter , and the 2-year recurrence-free survival rate was 85%.Cercek noted that the efficacy of immune checkpoint blockade appeared to be relatively tumor-agnostic, driven primarily by the MMRd phenotype rather than the tumor site of origin. She also said it’s likely that the effects seen are not specific to dostarlimab. “We don’t believe that it’s drug specific, rather just immune checkpoint blockade specific.” “The opportunity for patients to receive potentially curative immunotherapy without needing to go through surgery or other morbid therapies is just truly remarkable,” said Ryan B. Corcoran, MD, PhD, from Mass General Research Institute, Boston, who moderated the briefing and is co-chair of this year’s annual meeting clinical trials committee. Invited discussant Michael J. Overman, MD, with The University of Texas MD Anderson Cancer Center in Houston, said both operative and nonoperative approaches “can coexist” for early-stage MMRd solid tumors. He noted that “salvage surgery for incomplete responders after 6 months of PD-1 therapy does appear to be a successful approach. This is really a key take-home from this presentation.” Overman also emphasized the need for patient-centered discussions on which approach is best. “This is really up to the patient’s goal and based on a risk-benefit discussion,” he said. The study was supported by Swim Across America, GSK, Stand Up To Cancer, Haystack Oncology, the Simon and Eve Colin Foundation, and The Dalton Foundation and grants from the National Institutes of Health and the National Cancer Institute. Cercek disclosed having relationships with AbbVie, Amgen, Agenus, Daiichi Sankyo, GSK, Merck, Regeneron, Roche, and Pfizer. Overman disclosed having relationships with Roche, BMS, MedImmune, Merck, Amgen, Takeda, Janssen, Pfizer, Array, Gritstone bio, 3DMed, Nouscom, Atreca, Bayer, Lilly, and Phanes Therapeutics.All material on this website is protected by copyright, Copyright © 1994-2025 by WebMD LLC. This website also contains material copyrighted by 3rd parties.
Biologics Tumor Colorectal Cancer Colorectal Cancer (CRC) Endometrial Carcinoma Endometrial Cancer Carcinoma Of The Endometrium Cancer Of The Endometrium Cancer Malignant Neoplasia Carcinoma Malignant Neoplasm Malignant Rectal Neoplasm Rectal Cancer Cancer Of The Rectum Rectal Carcinoma Surgery Liquid Biopsy Fluid Biopsy Fluid Phase Biopsy Cancer Blood Test
United States Latest News, United States Headlines
Similar News:You can also read news stories similar to this one that we have collected from other news sources.
Immunotherapy Break Okay After Response in Metastatic MelanomaGood response rates were seen even after immunotherapy re-initiation following a drug holiday.
Read more »
Teddi Mellencamp's '50/50' Odds With Immunotherapy: Cancer Battle UpdateTeddi Mellencamp opens up about her cancer diagnosis, immunotherapy treatments, and how she finds humor and strength in a difficult time
Read more »
New immune boost could expand access to cancer immunotherapyResearchers have found that tapping into the body's own immune system and activating a type of immune cell known as B cells, could be the key to boosting the effectiveness of tumor-infiltrating lymphocyte, or TIL therapy.
Read more »
For some cancer patients, immunotherapy may be way to skip surgery and chemoKaitlin Sullivan is a contributor for NBCNews.com who has worked with NBC News Investigations. She reports on health, science and the environment and is a graduate of the Craig Newmark Graduate School of Journalism at City University of New York.
Read more »
Alternative cancer treatment could replace chemo and surgery, study suggestsA 'groundbreaking' cancer treatment trial by Memorial Sloan Kettering shows immunotherapy alone can eliminate some tumors, offering patients an alternative to chemotherapy and surgery.
Read more »
Immunotherapy drug capable of eliminating tumors in some early-stage cancers: StudyMost study participants were able to avoid operations after taking dostarlimab.
Read more »