Journal: The New England Journal of Medicine

Publishing date: June 5, 2022

Authors : A. Cercek et.al

PD-1 Blockade in Mismatch Repair: Deficient, Locally Advanced Rectal Cancer - Dostarlimab, an anti- PD-1 monoclonal antibody is found to be highly effective against mismatch repair-deficient locally advanced colorectal cancer with complete clinical resolution after treatment with the drug and no recurrence or progression of the disease over the follow-up period.

Why does this study matter?

Colorectal cancer is the second most common cancer in women and the third most common cancer in men affecting more than a million people globally every year. The standard therapy for colorectal cancer is neoadjuvant chemoradiotherapy followed by surgical resection. Programmed death 1 (PD-1) blockade was hypothesised to be effective in mismatch repair-deficient locally advanced colorectal cancer as metastatic mismatch repair-deficient colorectal cancer is responsive to PD-1 blockade.

Study Design

A prospective phase 2 study was initiated in which single-agent dostarlimab, an anti–PD-1 monoclonal antibody, was administered every 3 weeks for 6 months in patients with mismatch repair-deficient stage II or III rectal adenocarcinoma. Standard chemoradiotherapy and surgery were to be done after the treatment and those with clinical complete response after completion of dostarlimab therapy were to proceed without chemoradiotherapy and surgery. Sustained clinical complete response 12 months after completion of dostarlimab therapy or pathological complete response after completion of dostarlimab therapy with or without chemoradiotherapy and overall response to neoadjuvant dostarlimab therapy with or without chemoradiotherapy were the primary endpoints of the study.

Results and Conclusion

All 12 patients (100%; 95% confidence interval, 74 to 100) who completed treatment with dostarlimab and have undergone at least 6 months of follow-up had a clinical complete response. Magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy showed no evidence of tumour. At the time of this report, chemoradiotherapy or surgery was not done for any patient and no progression or recurrence was reported during the follow-up period (6 to 25 months). Adverse events of grade 3 or higher were not reported.

Single-agent PD-1 blockade with dostarlimab is highly effective in mismatch repair-deficient locally advanced colorectal adenocarcinoma and needs further long term follow-up to assess the duration of response.

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