Key phrase: results of Jemperli Dostarlimab in rectal cancers
At the ASCO (American Society of Clinical Oncology) Annual Conference, held in early June, there was much buzz around the results of an academic-sponsored clinical study’s findings that Jemperli (dostarlimab), a monoclonal antibody, had a 100% clinical complete response rate among a subset of patients with locally advanced rectal cancers.
In a CNN interview one of the lead researchers—Dr. Andrea Cercek, an oncologist with Memorial Sloan Kettering Cancer Center (MSKCC), stated: “What is really remarkable here is that it completely eliminated the cancer. The tumors just vanished” (Burnett, 2022)
In locally advanced cancer, the normal course of treatment includes induction chemotherapy in combination with chemoradiation and then surgery before surgery. This treatment usually results in approximately one-quarter of patients showing a pathologically complete response. At the same time, it often results in significant complications and toxic effects in a “substantial proportion” of patients, which can include infertility, and bowel, urinary, and sexual dysfunction. For those who require surgery, resection of the rectum is often life-altering for patients, requiring a permanent diverting colostomy (Cercek, et. al, 2022).
The findings of the study have implications for revolutionizing clinical practice in patients with mismatch repair-deficient localized advanced rectal cancer, with the possibility of completely curing those patients without the significant detrimental effects to their quality of life caused by surgery and chemoradiation. If the finding holds that every patient goes into sustained remission, it would be extremely rare. Indeed, reports say that Dr. Cercek, a veteran cancer researcher, was at times fighting back tears as she announced the results to ASCO (Plieth, 2022).
According to Dr. Cercek—who is Section Head for Colorectal Cancer and Co-Director of the Center for Young Onset Colorectal and Gastrointestinal Cancers at MSKCC —the treatment highlighted in the study, released in June in the New England Journal of Medicine, consists of immunotherapy involving the use of dostarlimab, a programmed death receptor-1-blocking (anti-PD-1) monoclonal antibody. It is intended to unlock the body’s natural immune system to fight specific rectal cancer cells, which are known as mismatch-repair deficient, meaning they lack a gene that enables them to repair their DNA. This can cause the immune system to be unable to recognize the cancer cells as foreign, allowing them to evade attack. So, when patients receive immunotherapy like dostarlimab, it enables the immune system to recognize and attack the cancer cell.
CNN’s Erin Burnett asked Dr. Cercek, “From your perspective, how remarkable is the outcome you observed?”
“It’s absolutely incredible,” Dr. Cercek responded. “We didn’t expect it. We’ve certainly never seen this before. It’s really what cancer doctors’ dreams are made of to see a response like this—such incredible efficacy with almost no toxicity. Our patients are feeling great after the treatment with completely normal body function in something like rectal cancer where normally our treatments are quite toxic” (CNN, 2022).
Fourteen patients with stage II and stage III rectal adenocarcinoma were treated with Jemperli every 3 weeks for 6 months. They also received chemoradiation and surgery. The study found that dostarlimab induces complete response in all 14 patients (with median follow-up of 6.8 months). This means that patients are effectively cured if their response is maintained, and they would not need chemoradiation or surgery. Additional patients are being enrolled in the continuing trial to confirm these early results.
Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody used as a medication for the treatment of endometrial cancer. On April 22, 2021, the FDA approved Jemperli (dostarlimab-gxly) for women with recurrent or advanced dMMR endometrial cancer (EC), as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen. On the next day, the European Union approved Jemperli for that indication.
On Aug. 17, 2021, GSK received FDA accelerated approval for JEMPERLI (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors.
For more details about the rectal cancer study release at ASCO, go to its ClinicalTrials.Gov Site at https://clinicaltrials.gov/ct2/show/NCT04165772
Burnett, E. (2022, June). ‘Tumors just vanished’: Cancer patients now in remission after drug trial. CNN (Video) https://www.cnn.com/videos/health/2022/06/07/cancer-study-shows-promise-in-trial-of-patients-rectal-cancer-intv-ebof-vpx.cnn/video/playlists/your-health/
Cercek, A., Lumish, J. Sinopoli, J., et al. (2022, June 5). PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa2201445
Plieth, J. (2022, June 17). The mystery of Jemperli’s rectal cancer breakthrough. Evaluate Vantage. https://www.evaluate.com/vantage/articles/events/conferences/mystery-jemperlis-rectal-cancer-breakthrough
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