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.)
這個稱為 PD 1 INHIBITOR 的藥, dostarlimab，
已經被用在晚期實體腫瘤的治療。效果和其他 PD 1 INHIBITOR 差不多。
研究人員在以下一組直腸癌病人進行試驗。
隻有十幾例。原意是先用此藥作＂引藥＂治療幾個月，等腫瘤縮小後，
在用標準療法：化療＋放射＋手術。
結果令人不敢相信：經過＞６個月的治療後，所有１２個病人（１００％）
都獲得臨床＂完全緩解＂！不需要化療＋放射＋手術！
在這裏給出我的看法：
１。病人的選擇。是一群２－３期的直腸癌患者。
已經４期 （有遠處轉移）的不算。而且是dMMR的亞型。
例數還小。相信很快就有到三期臨床實驗了 （多例數，對照實驗）。
2. 藥物：如果把這個藥用在其他４期腫瘤（有遠處轉移），
估計和其他的 PD 1 inhibitor差不多。
3. 如果你是一個病人，你要知道：是直腸癌？第幾期（有無遠處轉移）？
是 dmmr的亞型？有無 Pd 1 innibitor的禁忌症？
如果你通過這些條件，而且＂運氣＂好，你可能逃過標準療法:化療＋放射＋手術。
祝大家健康！
