PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer

Dostarlimab: A Review

“…Genes that should repair any improper activity to maintain cell health are absent in these types of cancer. Dostarlimab, an inhibitor of PD-1, demonstrated a long-lasting effect on dMMR tumors, and in 2022, reported a 100% remission rate for rectal cancer [ 4 ]. All patients had dMMR, a mutation present in 5 and 10% of rectal cancer cases (this mutation is also present in endometrial, prostate, and bladder tumors).…”

Jemperli (Dostarlimab-gxly): An unprecedented cancer trial

“…With colorectal cancer on the rise in world and no treatment strategies available which guarantee less invasive procedures, faster recovery period and higher survival rates, this drug could perhaps prove to be an effective management strategy in the future. Recently, it was known to have had a positive effect on treatment of colorectal cancer according to data from a phase 2 clinical trial; 12 patients with stage II/III mismatch repair deficient locally advanced rectal cancer underwent a clinical complete response of 100% with magnetic resonance imaging showing no evidence of residual tumor [ 5 ].…”

UpToDate®

“…Assessing subjective symptoms in patients undergoing RT may help reduce potential disparities in the diagnosis and management of radiation-related adverse effects, including dermatitis.immunotherapy for locally advanced rectal cancer with deficient mismatch repair (June 2022) Approximately 5 percent of rectal adenocarcinomas are deficient in DNA mismatch repair (dMMR), indicating potential responsiveness to immune checkpoint inhibitor immunotherapy. In a prospective study of 12 patients with stage II or III dMMR rectal cancer treated with dostarlimab monotherapy for 6 months, all 12 had a complete clinical response (radiographic and endoscopic), did not undergo chemoradiotherapy or surgery, and were free of residual or recurrent tumor with short-term follow-up (range 6 to 25 months) [2]. While this approach cannot yet be considered standard, individuals with dMMR tumors who place a high value on avoiding the long-term morbidity associated with surgery and pelvic radiation might choose this nonstandard approach if they are willing to accept the uncertainty of long-term outcomes, the small risk of fatal side effects from checkpoint inhibitors, and the need for very close follow-up.Pyelocalyceal mitomycin (Jelmyto) for low-grade upper tract urothelial carcinomas (may 2022) Pyelocalyceal mitomycin is used for patients with low-grade upper tract urothelial carcinoma (UTUC), but long-term efficacy data are lacking.…”