Therapy with pembrolizumab in treatment‐naïve patients with nonmetastatic, mismatch repair deficient colorectal cancer. Issue 10 (18th January 2023)

• Record Type: Journal Article
• Authors: Eefsen, Rikke Løvendahl; Larsen, Jim S.; Klarskov, Louise L.; Altaf, Rahim; Høgdall, Estrid; Ingeholm, Peter; Lykke, Jakob; Nielsen, Dorte L.; Pfeiffer, Per; Poulsen, Laurids Ø.; Qvortrup, Camilla; Schou, Jakob V.; Mau‐Sørensen, Morten; Østerlind, Kell; Jensen, Benny V.
• Is Part Of: International journal of cancer. Volume 152:Issue 10(2023)
• Page Start: 2145
• Page End: 2152
• Publication Date: 2023-01-18
• Subjects: checkpoint inhibition -- colorectal cancer -- mismatch repair deficient -- pembrolizumab -- unresectable; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.34420
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: Therapy with immune checkpoint inhibitors (ICI) is effective in patients with metastatic mismatch‐repair deficient (dMMR) colorectal cancer (CRC); however, data on treatment with neoadjuvant ICI in patients with locally advanced CRC are limited. From March 2019 to June 2020, five Danish oncological centers treated 10 patients with a treatment‐naïve dMMR CRC with preoperative pembrolizumab, 9 with a nonmetastatic, unresectable colon cancer and 1 with a locally advanced rectum cancer. All 10 patients were evaluated regularly at a multidisciplinary team (MDT) meeting, and they all had a radical resection after a median of 8 cycles (range 2‐13) of pembrolizumab. A microscopic evaluation of the resected tumors revealed no remaining tumor cells in five patients, while five still had tumor cells present. The patients were given no additional therapy. No recurrences were reported after a median follow‐up of 26 months (range 23‐38.5 months). Biopsies from Danish patients with CRC are routinely screened for dMMR proteins. In 2017, data from the Danish Colorectal Cancer Group showed that 19% (565/3000) of the patients with colon cancer and 1.5% (19/1279) of those with rectum cancer had an dMMR tumor. Among the patients with MMR determination, 26% (99/384) patients had a T4 dMMR colon cancer; thus, the 10 patients treated with neoadjuvant pembrolizumab comprised about 9% of the patients with a T4 dMMR colon cancer (9/99) and 5% of patients with dMMR rectal cancer (1/19). Therapy with pembrolizumab was feasible and effective. Larger prospective trials are needed to confirm our findings. Abstract : What's new? Therapy with immune checkpoint inhibitors is effective in patients with metastatic deficient mismatch‐repair (dMMR) colorectal cancer; however, data on neoadjuvant treatment with immune checkpoint inhibitors in patients with locally advanced disease are limited. In this multicenter study, initial therapy with pembrolizumab resulted in tumor shrinkage in 9 of the 10 treated patients with nonmetastatic dMMR colorectal cancer. Microscopic evaluation of the resected tumors revealed no remaining tumor cells in five patients, and no patient had recurrence at 26 months of follow‐up. The findings suggest that therapy with pembrolizumab is feasible and effective in this population.