Patients with rectal cancer with a genetic variation known as mismatch repair (dMMR) achieved a complete response when treated with Jemperli (dostarlimab), one of the newest checkpoint inhibitors, the researchers said. at the 2022 annual meeting of the American Society of Clinical Oncology (ASCO), which returned to Chicago this weekend after two years as a virtual conference. The findings were also published in The New England Journal of Medicine.
People who received Jemperli as their first line of treatment were able to avoid surgery, radiation, and chemotherapy, said study author Andrea Cercek, MD, of the Sloan Kettering Cancer Center Memorial.
Participants in the Jemperli Clinical Trial at the Sloan Kettering Cancer Center Memorial Courtesy of the Sloan Kettering Cancer Center Memorial
“I’m a miracle right here without any surgery, and I don’t have cancer,” said Imtiaz, one of four participants in clinical trials featured in a Sloan Kettering Memorial video about the study.
Rectal cancer, a rare malignancy associated with colon cancer, is often diagnosed at a later stage, when it is more difficult to treat. The standard treatment for locally advanced rectal cancer is neoadjuvant chemotherapy (surgery) and radiation to reduce tumors followed by surgery to remove all or part of the rectum, which may require a colostomy.
“Surgery and radiation have permanent effects on fertility, sexual health, bowel and bladder function,” Cercek said in a press release. “The implications for quality of life are substantial, especially in those where standard treatment would affect the potential for having children. As the incidence of rectal cancer increases in young adults, this approach can have a significant impact.”
This ongoing Phase II study (NCT04165772) enrolled 18 Sloan Kettering Memorial patients with stage II or III rectal adenocarcinoma with locally advanced mismatch repair deficiency. Two-thirds are women, most are white, and the average age is 54. Most have Lynch Syndrome, a genetic condition that causes a mismatched repair deficiency and increases the risk of colorectal cancer.
Cells are usually able to detect and repair errors that occur when DNA is copied during cell division. But tumors with mismatch repair deficiency do not have this mechanism, which means that mutations can build up and allow cells to grow out of control. Approximately 10% of colorectal tumors are deficient in mismatch repair. Metastatic dMMR colorectal cancer responds to control point inhibitors, which provides a justification for testing treatment at earlier stages.
Study participants were treated with Jemperli alone, given by IV infusion every three weeks for six months.
Jemperli is a monoclonal antibody immunotherapy that targets PD-1, a T-cell receptor that regulates immune function. Some tumors may sequester PD-1 to disable immune responses. Drugs that block the interaction between PD-1 in T cells and PD-L1, its tumor cell binding partner, can release the brakes and restore T-cell activity. Jemperli was first approved in April 2021 for advanced dMMR endometrial cancer; the indication was subsequently extended to all dMMR tumors regardless of location.
Initial treatment was intended to be followed by chemotherapy, radiation, and surgery, but this proved unnecessary. The 12 participants who completed the Jemperli course and were followed for at least six months achieved a complete remission, with no evidence of cancer remaining according to scans, digital rectal exams and biopsies. The rest of the patients with shorter follow-up have preliminary response tests. No one has relapsed so far, and follow-up continues to assess the duration of the response.
Jemperli was generally safe and well tolerated, and none of the participants experienced serious adverse events (grade 3 or higher) that can sometimes occur with immunotherapy at the checkpoint.
These results provide a framework for so-called immunoablative therapy, Cercek said. The findings highlight the importance of genomic testing to see if patients have mismatched repair deficiency tumors that are likely to respond to Jemperli. The lead author of the study Luis Diaz, Jr, MD, added that this approach could also work for other types of dMMR cancer, including pancreatic, stomach, and as yet non-metastatic prostate cancer.
Commenting on the study, Kimmie Ng, MD, MPH, of the Dana-Farber Cancer Institute, said that while the results are “unprecedented,” they still cannot be considered to change the practice until further confirmation. patients in other oncology centers with more time. carry on. Ultimately, researchers will look into whether Jemperli improves overall survival. However, a randomized clinical trial may be difficult to perform because rectal cancer is uncommon, and dMMR tumors are even rarer, and patients and their doctors may choose to use Jemperli off-label. based on this study.
Click here to read the study summary. Click here for more ASCO 2022 reports.
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