G. Buccafusca, S. Rametta Giuliano, P. Tralongo
Vol.3 (2018), issue 2, pag. 24-40

Received 25/06/2018
Accepted for pubblication 30/06/2018
Published June 2018
Review by Single-blind
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Metastatic colorectal cancer (mCRC) is the third leading cause of cancer deaths worldwide. Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30 months in recent clinical trials of first line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important. At the same time, longer life expectancy increases the number of elderly patients with colorectal cancer (CRC) potentially in need of oncology treatment. Unfortunately, elderly patients (≥65 years) often go untreated and they are also under-represented in clinical trials. Yet there is some evidence suggesting that ‘fit’ elderly patients have similar outcomes and tolerance to chemotherapy treatment to their younger counterparts. The evidence supporting the administration of new targeted therapies in patients older than 65 years is scarce and more research is needed. Recently, new options have entered the therapeutic field of treatment of mCRC beyond-line: Regorafenib is a multikinase inhibitor approved for mCRC patients who have progressed on chemotherapy (including fluoropyrimidines, irinotecan, and oxaliplatin), plus VEGF inhibitor(s) and – if RAS wild-type – an anti-EGFR inhibitor. Regorafenib significantly improved OS, compared to placebo, in two phase III trials (CORRECT and CONCUR) in mCRC patients. Trifluridine/Tipiracil, an oral fluoropyrimidine, also resulted in significantly improved OS when compared to placebo in the phase III RECOURSE trial, which was conducted in a similar patient population to CORRECT. However, the toxicity profile of TAS-102, substantially less impacting on the quality of life of the elderly patient and more manageable, makes it a valid therapeutic option compared to regorafenib in this setting of patients. In this paper, we review all the available data concerning the use of therapies for mCRC beyond second-line in patients older than 65 years of age and discuss the differences between this age subgroup and younger patients. Key words: Metastatic colorectal cancer, treatment beyond the second line, elderly, regorafenib, trifluridine/tipiracil