3393 - PIK3CA mutation in metastatic colorectal cancer (mCRC): association with clinico-pathological features and outcome

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.