The Role of Her2 in Locally Advanced Resectable Gastric Cancer as a Prognostic and Predictive Factor

Abstract

Background: Since 2010, the results of ToGA trial showed that Trastuzumab plus cisplatin-based chemotherapy (CHT) should be the new standard therapy for patients ( pts) with HER2-positive (HER2+) advanced gastric cancer, improving overall survival (OS) and progression-free survival (PFS). Nonetheless, there is still scarce evidence regarding the role of HER2 status in pts with locally advanced resectable gastric cancer (LARGC). Our aim was to assess if HER2+ in LARGC could be a prognostic factor correlated to a poor survival outcome and a predictive factor of response to standard perioperative CHT in our area. Methods: We retrospectively reviewed 65 pts with LARGC who were planned to receive perioperative chemotherapy followed by surgery, between May 2008 and February 2012, at Institut Català d'Oncologia (ICO) Hospitalet. We analyzed the correlation between mOS, mPFS, pathological downstaging and histological tumour regression rate (TRR) with HER2 status. In HER2+ pts, we assumed their HER2 overexpression if their tumours were scored as 3+ on immunohistochemistry (IH) or 2 + IH with gene amplification by SISH. OS and PFS were analyzed using Kaplan-Meier curves and the differences with the Log-Rank test. Results: 16 women and 49 men were analyzed, with a median age of 63 years (range 38-78). 41% pts had a diffuse type, 49% an intestinal type and 10% a mixt type adenocarcinoma. We found 12 pts HER2+ and 53 pts HER2-. 30% of tumours were proximal and 70% were distal. There were clinically 1.6% stage I, 49.2% stage II and 49.2% stage III pts. 58 pts (98%) completed 3 cycles of neoadjuvant chemotherapy. 42 pts received ECF, whereas 23 pts received other schemes (13 pts carboplatin + 5FU, 8 pts cisplatin + 5FU, 2 pts other combinations). 64 patients had a radical surgery, and there was only 1 pt who underwent a palliative derivation. We found 1 surgery-related death. Adjuvant chemotherapy was delivered in 45 pts. We did not reach neither the mOS nor the mPFS, given that more than 50% pts in both groups were alive at the analysis. Pathological downstaging was obtained in 54.5% pts HER2+ (95% CI, 23.4-83.2) and in 36.7% pts HER2- (95% CI, 23.4-51.7), and downstaging in terms of TRR (RG1 + RG2 + RG3) was obtained in 54.5% pts HER2+ (95% CI, 23.4-83.2) and in 38.8% pts HER2- (95% CI, 25.2-53.8). Conclusion: 18% pts were HER2+ in our study population. We did not reach neither mOS nor PFS to correlate HER2 status as a prognostic factor. HER2+ pts seemed to respond with standard CHT, but we did not have enough pts to achieve statistical results. Several clinical trials are currently exploring the potential role of anti-HER2 therapies in the neoadjuvant setting, but there is still a great need to clarify the value of HER2 status as a predictive and prognostic factor in LARGC that would allow the clinicians to make a more personalized therapy to our gastric cancer patients.