Since the HERACLES trial demonstrated a favorable response of ERBB2 positive metastatic colorectal cancer (mCRC) patients to Trastuzumab (Herceptin®) and Lapatinib (Tykerb®) combination therapy, ERBB2 alterations have become a new target alteration in mCRC. To evaluate whether such therapies may also be suitable for the adjuvant setting, researchers are interested in the prognostic influence of ERBB2 alterations in mCRC. To this end, the ERBB2 genetic profile of 1795 mCRC patients’ tissue samples from the PETACC8 trial was analyzed by next-generation sequencing (NGS). ERBB2 mutations were detected in 17 patients (1%), the most frequent ERBB2 mutations being p.V842I in five patients, p.V777L in three patients and p.L755S in three patients. Besides, 49 patients (2.9%) harbored ERBB2 amplifications. ERBB2 alterations were correlated with both shorter time to recurrence (HR: 1.55; 95% Cl: 1.02-2.36; p=0.04) and shorter overall survival (HR: 1.57; 95% Cl: 0.99-2.5; p=0.04). In conclusion, ERBB2 alterations were associated with a poor prognosis in stage III CRC patients. These findings provide a rationale for testing anti-ERRB2 therapies in the adjuvant setting.
1. ESMO 2016 abstract:
Gettinger SN., et al., Lancet Oncol. 17:1683-1696, 2016. DOI: 10.1016/S1470-2045(16)30392-8.
2. Laurent-Puig., et al., ESMO 2016 abstract 4590：
Annals of Oncology 27 (Supplement 6): vi149–vi206, 2016. DOI: 10.1093/annonc/mdw370.8
3. 2016 ESMO news article: