Anti-PD-L1 immunotherapy combined with MEK inhibitor for metastatic colorectal cancer

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At the 18th World Congress of Gastrointestinal Cancer, a phase I clinical study showed that anti-PD-L1 immunotherapy combined with MEK inhibitors can effectively treat microsatellite stable metastatic colorectal cancer.

The lead investigator of the study, Johanna Bendell of the Sarah Cannon Cancer Institute, pointed out: So far, immunotherapy has only been effective for patients with highly microsatellite unstable colorectal cancer, and this type of patients accounts for only 5% of the population.

Highly microsatellite unstable colorectal cancer has a larger number of mutations and therefore responds to anti-PD-1 / PD-L1 immunotherapy. However, about 95% of patients with metastatic colorectal cancer have microsatellite stable foci. So far, this part of patients has hardly responded to immunotherapy.

Preclinical studies suggest that MEK inhibitors can make tumors more sensitive to immunotherapy. The specific mechanism may be to increase the number of active immune cells (such as CD8 positive cells) in the tumor and increase the expression of pro-immune system activation factors.

The results of the study showed that the Phase I b clinical study used the MEK inhibitor Cobimetinib to treat 23 patients with treated colorectal cancer according to the dose-climbing regimen. (Q3W), most patients can tolerate large doses and are treated with 800 mg of PD-L1 inhibitor Atezolizumab (intravenous injection, Q2W).

In the follow-up treatment, the researchers observed that 4 patients (17%) had a tumor shrinkage of at least 30%, and 5 patients (22%) had stable disease. The continuous remission time is more than 4 ~ 15 months. As of the current data, 2 out of 4 patients with partial remission have achieved continuous remission. Among patients with partial remission, 3 cases were microsatellite stable or low-level microsatellite instability, and 1 case had unknown microsatellite status. Among the patients included in the study, there were no cases of highly unstable microsatellites.

In addition, the baseline level of PD-L1 does not affect disease remission, the combination medication is well tolerated, and there are no serious treatment-related adverse events.

Bendell concluded: “The results of the study are consistent with the hypothesis of combination therapy, which also provides another 95% of colorectal cancer patients with an opportunity to receive immunotherapy.” The investigator is about to launch a phase III clinical study, planning to enter the group is difficult For curative metastatic colorectal cancer, compare the efficacy of this combination therapy with standard regimens.

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