Facts Matter with Roman Balmakov
PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer
Abstract
Background
Neoadjuvant
chemotherapy and radiation followed by surgical resection of the rectum
is a standard treatment for locally advanced rectal cancer. A subset of
rectal cancer is caused by a deficiency in mismatch repair. Because
mismatch repair–deficient colorectal cancer is responsive to programmed
death 1 (PD-1) blockade in the context of metastatic disease, it was
hypothesized that checkpoint blockade could be effective in patients
with mismatch repair–deficient, locally advanced rectal cancer.
Methods
We
initiated a prospective phase 2 study 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. This treatment was to be followed by
standard chemoradiotherapy and surgery. Patients who had a clinical
complete response after completion of dostarlimab therapy would proceed
without chemoradiotherapy and surgery. The primary end points are
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.
Results
A
total of 12 patients have completed treatment with dostarlimab and have
undergone at least 6 months of follow-up. All 12 patients (100%; 95%
confidence interval, 74 to 100) had a clinical complete response, with
no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission
tomography, endoscopic evaluation, digital rectal examination, or
biopsy. At the time of this report, no patients had received
chemoradiotherapy or undergone surgery, and no cases of progression or
recurrence had been reported during follow-up (range, 6 to 25 months).
No adverse events of grade 3 or higher have been reported.
Conclusions
Mismatch
repair–deficient, locally advanced rectal cancer was highly sensitive
to single-agent PD-1 blockade. Longer follow-up is needed to assess the
duration of response. (Funded by the Simon and Eve Colin Foundation and
others; ClinicalTrials.gov number, NCT04165772.)
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Facts Matter with Roman Balmakov
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