Fulvestrant with or without selumetinib, a MEK 1/2 inhibitor, in breast cancer progressing after aromatase inhibitor therapy: A multicentre randomised placebo-controlled double-blind phase II trial, SAKK 21/08

Risk of selected gastrointestinal toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis

“…Our analysis of data demonstrated an increased risk of all-grade stomatitis, diarrhea and vomiting with MEK inhibitor-based [13] Flaherty et al chemotherapy (2012) [20] Flaherty et al combination (2012) [23] Infante et al (2014) [24] Long et al (2014) [22] Robert et al [15] Total treatment compared with control. Additionally, high-grade diarrhea was also increased with MEK inhibitors versus control.…”

“…The details for study inclusion/exclusion procedure are illustrated in FIGURE 1. . A total of 16 RCTs were considered eligible for the analysis [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] [20] Robert et al Long et al [23] Infante et al [25] Selumetinib studies…”

“…GI mucosal injury is considered an important cause for treatment interruption and/or permanent discontinuation in RCTs of Blumenschein et al (2015) [ [13] Flaherty et al chemotherapy (2012) [20] Flaherty et al combination (2012) [23] Infante et al (2014) [24] Long et al (2014) [22] Robert et al [15] Total events Heterogeneity: Tau MEK inhibitors; moreover, we do not have currently any clear methods to predict patients at highest risk and thus regular monitoring of patients receiving these agents is of utmost significance. GI toxicities have long been reported also in a number of other targeted therapeutics used in cancer management and, likewise, they have been linked to dose reduction and/or interruption [32,33].…”

“…Hence, a more thorough comprehension of the driving mechanisms is much required to bring in more compelling therapies for these toxicities. Blumenschein et al (2015) [ [13] Flaherty et al chemotherapy (2012) [20] Flaherty et al combination (2012) [23] Infante et al (2014) [24] Long et al (2014) [22] Robert et al (2015) [21] S Bennouna et al (2011) [11] S Bodoky et al (2012) [19] S Carvajal et al (2014) [26] S Gupta et al (2014) [14] S Hainsworth et al (2010) [27] S Jänne et al (2013) [17] S Kirkwood et al (2011) [28] S Robert et al (2013) [16] S Zaman et al (2015) [15] Total events Heterogeneity: Chi 2 = 8.69, df = 12 (p = 0.73); I 2 = 0% Test for overall effect: Z = 1. 30 [13] Flaherty et al chemotherapy (2012) [20] Flaherty et al combination (2012) [23] Infante et al (2014) [24] Long et al (2014) [22] Robert et al (2015) [21] S Bennouna et al (2011) [11] S Bodoky et al (2012) [19] S Carvajal et al (2014) [26] S Gupta et al (2014) [14] S Hainsworth et al (2010) [27] S Jänne et al (2013) …”

“…(2015)[21] SBennouna et al (2011) [11] SBodoky et al (2012) [19] SCarvajal et al (2014) [26] SGupta et al (2014) [14] S Hainsworth et al (2010)[27] SJänne et al (2013) [17] SKirkwood et al (2011) [28] SRobert et al (2013) [16] SZaman et al (2015) …”