Therapy with pembrolizumab in treatment-naïve patients with non-metastatic, mismatch repair deficient colorectal cancer

Rikke L Eefsen*, Jim S Larsen, Louise L Klarskov, Rahim Altaf, Estrid Høgdall, Peter Ingeholm, Jakob Lykke, Dorte L Nielsen, Per Pfeiffer, Laurids Ø Poulsen, Camilla Qvortrup, Jakob V Schou, Morten Mau-Sørensen, Kell Østerlind, Benny V Jensen

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

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.

OriginalsprogEngelsk
Sider (fra-til)2145-2152
Antal sider8
TidsskriftInternational Journal of Cancer
Vol/bind152
Udgave nummer10
Tidlig onlinedato3 jan. 2023
DOI
StatusUdgivet, E-publikation før trykning - 3 jan. 2023

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© 2023 UICC.

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