Colon Cancer...systemic therapy...([Nivolumab +/- ipilimumab] or pembrolizumab [preferred]) (dMMR/MSH-I only)

Merck...announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in adults with...unresectable or metastatic gastric, small intestine or biliary cancer, who have disease progression on or following at least one prior therapy.

...Histologically proven adenocarcinoma of the colon or rectum which is MMR-d by IHC or MSI-H by PCR (or microsatellite testing if routine practice)....

...Histologically confirmed localized dMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colon carcinoma....

...• Signed written informed consent; • Patients at least 18 years of age; • Locally advanced, irresectable adenocarcinoma of the colon or rectum, not amenable to surgery, or for which induction therapy is required to reconsider surgery, or where free margins can only be obtained by major extension of the surgical procedure, as defined by one of the following: o Invasion of the duodenum, stomach, spleen or pancreatic head, for which major extension of the surgical procedure would be required to obtain free margins, and/or for which the chances of positive resection margins are high o Invasion or encasement of major blood vessels (superior mesenteric vessels, iliac vessels, portal vein) o Invasion or encasement of the ureter • Histologically or cytologically confirmed microsatellite instability-high (MSI-H) or MMR-deficient (dMMR) status• No signs of distant metastases on CT-scan and physical examination; patients may not be eligible for first-line treatment with pembrolizumab according to SoC • Patients may not be eligible for standard of care first-line pembrolizumab for metastatic disease • Patients may not be potentially eligible for the NICHE study: patients with primarily resectable disease, for which relatively minor extension of the procedure is required to acieve free margins, such as but not limited to a small bowel segment, abdominal wall• ECOG performance status of 0 or 1. ...

With three cycles of oxaliplatin plus pembrolizumab 74.4% of high risk dMMR stage III colon cancer achieved PCR….so, this combo could be more validated in both neoadjuvant and adjuvant high risk dMMR stage III colon cancer in the future.

CONTRADICTING EVIDENCE: An 80-year-old female visited our hospital with complaints of lower abdominal pain due to bowel obstruction caused by descending colon cancer….Based on the genetic finding of MSI-H status, pembrolizumab therapy was administered in two cycles. Unfortunately, the therapy was ineffective, and the patient died after being discharged 5 months after surgery.

A 74-year-old patient was diagnosed with a locally advanced dMMR adenocarcinoma in the transverse colon with clinical suspicion of peritoneal metastases (cT4N2M1)….After 5 months of treatment with pembrolizumab, a complete radiological response in the primary tumour was seen although there was still radiological suspicion of peritoneal and lymph node metastases....

Herein, we report a case of pathological complete response of MSI-H clinical T4b ascending colon cancer to preoperative treatment with pembrolizumab. After 2 cycles of therapy with pembrolizumab (200 mg/body on day 1 every 3 weeks), there was drastic tumor regression. In addition, computed tomography indicated that all lymph node metastases had disappeared.