Disease control rates were similar between patients with WT (91%) and MT (92%) mCRC and were slightly higher in the WT/WT (95%) group than in those with or MT (89%) mCRC (Table 2)

Disease control rates were similar between patients with WT (91%) and MT (92%) mCRC and were slightly higher in the WT/WT (95%) group than in those with or MT (89%) mCRC (Table 2). Table 2 Best response, objective response and disease control rates (%)?????Complete response2 (3)1 (1)2 (3)1 (1)?Partial response38 (56)29 (40)38 (64)29 (35)?Stable disease22 (32)37 (51)16 (27)43 (52)?Disease progression5 (7)3 (4)2 (3)6 (7)?Unevaluable/not done1 (1)3 (4)1 (2)3 (4)Objective response, (%) [95% CI]40 (59) [46.2, 70.6]30 (41) [29.7, 53.2]40 (68) [54.4, 79.4]30 (37) [26.2, 48.0]Unadjusted odds ratio (95% CI)2.0 (1.0, 4.2)(%) [95% CI]62 (91) [81.8, 96.7]67 (92) [83.0, 96.9]56 (95) [85.9, 98.9]73 (89) [80.2, 94.9]Unadjusted odds ratio (95% CI)0.9 (0.2, 3.7)2.3 EPZ004777 hydrochloride (0.5, 13.8) Open in a separate window Abbreviations: CI=confidence intervals; MT=mutant; WT=wild type. The DoR analysis included only those patients who experienced a partial or complete response: 40 patients with mCRC WT for both and and WT mCRC (no patient with MT disease responded to treatment). months; HR, 0.37) and was also longer in WT/WT or MT (13.2 6.9 months; HR, 0.25). Incidence of adverse events was comparable regardless of status, and no new safety signals were noted. Among patients with WT tumours, ORR was 67% with high AREG expression and 38% with low AREG expression. Conclusions: First-line panitumumab+FOLFIRI was associated with favourable efficacy in patients with WT and WT/WT MT mCRC tumours and was well tolerated. wild-type (WT) mCRC. In the first-line setting, EGFR inhibitors were originally indicated in patients with WT mCRC in combination with either FOLFOX (panitumumab or cetuximab) or FOLFIRI (cetuximab). Subsequently, mutations were identified in and in 17% of patients with non-mutated exon 2 in the phase III Primary trial of panitumumab + FOLFOX FOLFOX alone (Douillard WT disease. At the same time, studies also identified as an important unfavorable prognostic C though not predictive C marker for survival in patients with mCRC, regardless of treatment (Phipps status was later verified in trials of first- and second-line FOLFOX and FOLFIRI in combination with panitumumab or cetuximab (Douillard mutant (MT) tumours showed no improvement in efficacy with the addition of EGFR inhibitor compared with chemotherapy alone. Indeed, there is some evidence that EGFR inhibitors combined with FOLFOX in such patients are detrimental compared with FOLFOX alone (Douillard MT tumours. Panitumumab plus FOLFIRI exhibited superiority over FOLFIRI alone in a second-line phase II trial that exhibited improved progression-free survival (PFS) in patients with WT mCRC, although overall survival (OS) was not significantly different in this study (Peeters WT patients (K?hne WT colorectal cancer and liver-limited disease (Abad status and AREG levels in patients with mCRC. Rabbit Polyclonal to C-RAF (phospho-Ser301) Patients and methods Study design This is a retrospective analysis of data from a phase II, single-arm study (“type”:”clinical-trial”,”attrs”:”text”:”NCT 00508404″,”term_id”:”NCT00508404″NCT 00508404); full details of the study design have been presented previously (K?hne status. Tumour specimens were assayed for mutations in exons 3C4, exons 2C4 and exon 15 by bidirectional Sanger sequencing. Mutations in exon 2 were analysed by CE-marked DxS kit. Baseline tumour AREG levels were analysed in the WT and MT populations. Total RNA was extracted from formalin-fixed paraffin-embedded tissue samples and AREG expression levels were analysed by qualified reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays (see Supplementary Material for details). A cutoff point for AREG status was prespecified based on analysis of data from an earlier clinical trial (STEPP) (Lacouture mutational analysis therefore included 150 patients, of whom 143 received at least one dose of panitumumab. Overall, 38% of patients had exon 2 mutations, and 10% had mutations beyond exon 2 (exon 3 and 4 mutations each in 3% of tumours; exon 2 and 3 mutations each in 2% of tumours; no tumour was found to carry an exon 4 mutation). Complete data were available for 143 of 150 patients, of whom 69 (45%) had WT tumours (i.e., WT for exons 2, 3 and 4 of both and mutations were present in nine patients (6%), all of whom had tumours that were WT for WT MT mCRC, and between patients with WT/WT and or MT status (Table 1). More patients with WT and WT/WT mCRC had liver-limited metastases, whereas more MT and or MT patients had metastases at other sites only. The sum of the longest diameters of measurable target lesions was also slightly larger in patients with WT and WT/WT mCRC compared with the corresponding MT populations. The median follow-up time in the study was 34.0 weeks EPZ004777 hydrochloride (range, 5C223 weeks). Table 1 Baseline demographics and disease characteristics (%)55 (80)42 (57)50 (83)47 (57)White ethnicity, (%)66 (96)73 (99)57 (95)82 (99)Age (years), median (range)62.2 (38C84)63.7 (37C80)64.5 (38C84)64.0 (37C80)ECOG PS, (%)?????0/166 (96)69 (93)57 (95)78 (94)?23 (4)5 (7)a3 (5)5 (6)aPrimary tumour, (%)?????Colon40 (58)48 (65)34 (57)54 (65)?Rectum29 (42)26 (35)26 (43)29 (35)Time since mCRC diagnosis (months),b median (range)1.1 (0C29)1.2 (0C44)1.0 (0C29)1.2 (0C44)Number of metastatic sites, (%)?????130 (43)31 (42)27 (45)34 (41)?222 (32)25 (34)18 (30)29 (35)??317 (25)18 (24)15 (25)20 (24)Sites of metastases, (%)?????Liver only26 EPZ004777 hydrochloride (38)20 (27)24 (40)22 (27)?Liver + other33 (48)35 (47)29 (48)39 (47)?Other only10 (14)19 (26)7 (12)22 (27)Sum of longest diameters of measurable lesions (mm),c median (range)135.5 (20C381)107.0 (20C371)136.0 (20C381)104.0 (20C371) Open in a separate window Abbreviations: ECOG PS=Eastern Cooperative Oncology Group performance status; mCRC=metastatic colorectal cancer; MT=mutant; WT=wild type. aOne patient in the mutant group had an ECOG PS of 3. bDate of enrolment minus date of primary diagnosis or metastatic disease. cTarget.