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In metastatic colorectal cancer (mCRC) with misalising repair skill (MMR-P), immuno-checkpoint inhibitors (ICI) alone do not achieve the desired results, nor does radiotherapy (RT) alone provide objective systemic benefits.
, however, in preclinical and clinical models, a combined application of RT and ICI can induce systemic anti-tumor immunity.
in this single-center Phase II study, patients with chemotherapy's incurable MMR-P mCRC were recruited to be treated with durvalumab (1500mg) and tremelimumab (75mg) every 4 weeks, plus RT.
end point is the objective response rate (ORR) of non-radiation lesions.
treatment and efficacy are related to the exoimmune cell spectrum.
24 patients were recruited, with a medium follow-up time of 21.8 months (range: 15.9-26.3 months).
ORR is 8.3% (2/24) (95% CI 1.0% to 27.0%).
the medium non-progressing lifetime was 1.8 months (95% CI 1.7 to 1.9 months) and the total survival period was 11.4 months (95% CI 10.1 to 17.4 months).
25% of patients (n-6) had treatment-related level 3-4 adverse events.
, the researchers observed an increase in the activity, differentiation and proliferation of CD8-T lymphocytes in circulating blood in patients with objective reactions.
, the ICI-RT joint scheme evaluated in this study did not reach the pre-specified primary endpoint.
, however, the researchers observed a rare systemic immune enhancement and subsidion (an abnormal reaction) in non-radioactive lesions.
a combined treatment of MMR-P mCRC patients with Durvalumab and Tremlimumab-RT is feasible and safe and controllable.
further study of the new joint immunotherapy programme and the identification of biomarkers that can predict abnormal reactions.