Continuation of targeted therapy after disease progression

Abstract

Continuation despite the progression seems at first glance justified in the case of targeted drugs aimed at molecular pathways on which the tumour is dependent (oncogene addiction). Glivec and chronic myeloid leukemia and GIST is an illustration of this phenomenon, but in the case of common solid tumours such as lung cancer, pancreatic cancer, breast cancer, molecular heterogeneity of the tumour cell subpopulations makes further treatment after progres­sion risky. It may actually not inhibit, but accelerate the disease. Clinical proof of this are recently presented results of the IMPRESS study in NSCLC, where continued treatment with kinase inhibitor and chemotherapy after progression caused shortened overall survival, Experimental explanation of this phenomenon makes relevant the work involving vemurafenib and melanoma in the mouse model, in which continued treatment leads to accelerated progression and, on the contrary, a pause in treatment (drug holiday) caused inhibition of tumour growth. The use of continued treatment after progression in colon cancer with bevacizumab was associated with extended time to progression (the effect is statistically significant but clinically minimal), which forces us to reflect on clinical trials, in which a small clinical benefit is obtained but engages thousands of patients.