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. opens in new tab.)

这个称为 PD 1 INHIBITOR 的药, dostarlimab，

已经被用在晚期实体肿瘤的治疗。效果和其他 PD 1 INHIBITOR 差不多。

研究人员在以下一组直肠癌病人进行试验。

只有十几例。原意是先用此药作＂引药＂治疗几个月，等肿瘤缩小后，

在用标准疗法：化疗＋放射＋手术。 
结果令人不敢相信：经过＞６个月的治疗后，所有１２个病人（１００％）

都获得临床＂完全缓解＂！不需要化疗＋放射＋手术！

在这里给出我的看法：
１。病人的选择。是一群２－３期的直肠癌患者。

已经４期 （有远处转移）的不算。而且是dMMR的亚型。

例数还小。相信很快就有到三期临床实验了 （多例数，对照实验）。

2. 药物：如果把这个药用在其他４期肿瘤（有远处转移），

估计和其他的 PD 1 inhibitor差不多。

3. 如果你是一个病人，你要知道：是直肠癌？第几期（有无远处转移）？

是 dmmr的亚型？有无 Pd 1 innibitor的禁忌症？

如果你通过这些条件，而且＂运气＂好，你可能逃过标准疗法:化疗＋放射＋手术。
祝大家健康！