Abstract 3393
Background
Mutations in PIK3CA, an EGFR downstream effector, and the subsequent activation of AKT pathway plays an important role in colorectal carcinogenesis. Considering the frequent co-occurrence of PIK3CA and RAS mutations, conflicting data exist about its impact on prognosis of mCRC patients (pts) and its predictive role to anti-EGFR therapy. However, PI3K inhibitors have been developed and are currently under investigation in mCRC.
Methods
Data from mCRC pts treated at Azienda Ospedaliero-Universitaria Pisana from 1 Jan 2005 to 31 Dec 2017, whose tumours had been analysed per clinical practice by MALDI-TOF MassArray were retrieved. Association between PIK3CA mutation and clinico-pathological features was analysed by χ2 test; OS curves were estimated with Kaplan-Meier method and compared by log-rank test.
Results
Tumours from 90 (17%) out of 542 pts included in this analysis were PIK3CA mutated (mut), most of them in exon 9 (58.9%) or 20 (21.1%). Compared to PIK3CA wild-type (wt) tumours, mut ones were more often RAS mut (P = 0.006), MSI high (P = 0.008), and right-sided (P = 0.0004). Among 53 pts for whom PIK3CA status was available on both primary tumours (PT) and metastasis, the concordance was 92.4%. PIK3CA mutations were not associated with OS (36.4 vs 35.9 mos, HR 1.17, 95%CI 0.85-1.62, p = 0.3), with no difference among those affecting exon 9 and 20 (36.4 vs 27.5 mos, HR 0.77, 95%CI 0.39-1.54, p = 0.44). In RAS/BRAF wt (N 188) and in RAS mut (N 299) subgroup, no difference in terms of OS was found between PIK3CA mut and wt pts (38.1 vs 44.4 mos, HR 1.22, 95%CI 0.60-2.48, p = 0.55 and 27.5 vs 34.4 mos, HR 1.26, 95%CI 0.85-1.86, p = 0.22, respectively), though PIK3CA mut had shorter OS. In BRAF mut subgroup (N 54), PIK3CA mut pts had longer OS compared to PIK3CA wt (not reached vs 14.4 mos, HR 0.37, 95%CI 0.16-0.85, p = 0.09). Among 39 chemorefractory RAS/BRAF wt pts evaluable for response to an anti-EGFR agent, only 2 were exon 9 PIK3CA mut and achieved stable disease.
Conclusions
PIK3CA mut tumours displayed specific clinico-pathological features and a strong concordance was found between PT and paired metastases. Interestingly, a different impact on prognosis of PIK3CA mutation in RAS/BRAF wt, RAS mut or BRAF mut mCRC pts was observed and deserves validation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Supported by ARCO (Associazione Ricerca e Cure in Oncologia) Foundation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5205 - Immune status of patients with different stages of colorectal cancer with and without circulating tumor cells
Presenter: Anastasia Sitkovskaya
Session: Poster Display session 2
Resources:
Abstract
5658 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Early Diagnosis of Colorectal Cancer
Presenter: Tianyu Liu
Session: Poster Display session 2
Resources:
Abstract
5779 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Prediction of The Efficacy of Conversion Therapy for Colorectal Cancer Liver Metastases
Presenter: Wenju Chang
Session: Poster Display session 2
Resources:
Abstract
4672 - mCRC gene profiling using the Idylla platform
Presenter: Christopher Bricogne
Session: Poster Display session 2
Resources:
Abstract
1317 - Patient-Derived Xenografts (PDX) Identifies JMJD6 Inhibitor as an Effective Therapeutic Medicine in Colorectal Cancer.
Presenter: Feng Ye
Session: Poster Display session 2
Resources:
Abstract
1228 - DACH1 induced stemness of intestinal organoids by directly suppressing BMP signaling and contributes to intestinal tumorigenesis
Presenter: Xiang Hu
Session: Poster Display session 2
Resources:
Abstract
1147 - miR-148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF-1α under non-hypoxia/hypoxia conditions
Presenter: Hsiang-lin Tsai
Session: Poster Display session 2
Resources:
Abstract
1158 - Long noncoding RNA CASC21 promotes cell proliferation and metastasis in colon cancer.
Presenter: Qun Zhang
Session: Poster Display session 2
Resources:
Abstract
1259 - Prognostic and Predictive Impact On FMS-like Tyrosine Kinase 3 (FLT3) Amplification In Patients With Metastatic Colorectal Cancer
Presenter: Hiroko Hasegawa
Session: Poster Display session 2
Resources:
Abstract
1452 - RBP-Jκ in colon cancer cells facilitates tumor associated macrophages (TAMs)-induced cell metastasis by secreting CXCL11
Presenter: Meng jie Liu
Session: Poster Display session 2
Resources:
Abstract