In addition, late relapses are now emerging with longer follow-up of clinical trial populations, suggesting the emergence of acquired resistance. However, initial response appears to be a binary event, with most non-responders to single-agent ICI therapy progressing at a rate consistent with the natural history of disease.
While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI. Whereas cytotoxic chemotherapy and small molecule inhibitors (‘targeted therapies’) largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology.
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