A Systematic Review and Meta-analysis of Retrospective Series of Regorafenib for Treatment of Metastatic Colorectal Cancer

Abstract

Colorectal cancer is the most common gastrointestinal malignancy in the Western world and remains a prominent cause of cancer morbidity and mortality, despite progress in its management. It affects approximately 746,000 men and 614,000 women yearly and it is the 3rd most common cancer in the former and the 2nd most common in the latter (1). About one fourth of newly-diagnosed colorectal cancers are already in a metastatic stage and of those that are diagnosed in a localized stage nearly 50% will go on to develop metastatic disease, in most cases becoming unresectable. Metastatic colorectal cancer treatment options have been broadened to include regimens of oxaliplatin or irinotecan added to a fluoropyrimidine backbone, as well as targeted treatments with bevacizumab and, for KRAS wild-type tumors, cetuximab or panitumumab (2-4). These treatments have extended the median survival of patients with metastatic colorectal cancer to over 2 years. Nevertheless, the disease remains incurable in most patients and when the above drug options have been exhausted, there is a paucity of other options. This therapeutic vacuum has been partially filled recently with the approval of the tyrosine kinase inhibitor regorafenib, a fluorinated derivative of sorafenib, for the third line treatment of metastatic colorectal cancer patients (5).Regorafenib (formerly known as BAY 73-4506; chemical formula: C 21 H 17 CIF 4 N 4 O 4 ) is a small molecule multi-kinase inhibitor of fms-related tyrosine kinase 1 (FLT1, also known as vascular endothelial growth factor receptor 1, VEGFR1), 5925

<p>Regorafenib for Metastatic Colorectal Cancer: An Analysis of a Registry-Based Cohort of 555 Patients</p>

“…Nevertheless, a metaanalysis of retrospective studies has confirmed the efficacy results from randomized and other prospective studies, yielding a median OS of 7.3 months. 13 The fact that only a minority of patients treated with third-line agents for mCRC including regorafenib and trifluridine-tipiracil respond to therapy has spurred the search for a clinically useful prognostic index to identify patients with higher likelihood of benefit. The ColonLife nomogram based on the presence of primary tumor, lactate dehydrogenase level, performance status, and peritoneal involvement, has been validated in this setting and there are other sets of variables that may provide a tool for treatment individualization.…”

“…Nevertheless, a meta-analysis of retrospective studies has confirmed the efficacy results from randomized and other prospective studies, yielding a median OS of 7.3 months. 13 …”

Keratin 80 promotes migration and invasion of colorectal carcinoma by interacting with PRKDC via activating the AKT pathway

“…Although prominent advances have been made in the treatment of colorectal carcinoma (CRC), it remains the most common gastrointestinal cancer worldwide, with high morbidity and mortality rates 1 . Around 25% of newly diagnosed patients with CRC have metastasis, whereas ~ 50% of patients with localized tumors will eventually develop metastasis, with most of these tumors being unresectable 2 .…”

Impact of sex, body mass index and initial pathologic diagnosis age on the incidence and prognosis of different types of cancer

“…To investigate which types of cancer are associated with younger patients, all cases in the TCGA database were grouped by the initial pathologic diagnosis age. They were divided into 9 groups: Group 1 (≤10) (no >10 years old); group 2 ( 10 – 20 ); group 3 ( 21 – 30 ); group 4 ( 31 – 40 ); group 5 ( 41 – 50 ); group 6 ( 51 – 60 ); group 7 (61–70); group 8 (71–80); and group 9 (>80 years). Cancer occurred in every age group.…”