P-350 Maintenance trastuzumab in the setting of second-line treatment in HER2 overexpressing metastatic gastric and gastroesophageal junction adenocarcinoma: Experience of our centre

Abstract

Standard of care (SOC) in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma after progression to 1st line platinum/ fluoropyrimidine-based treatment is the combination of paclitaxel and ramucirumab (P/R), based on the results of the RAINBOW trial. Trastuzumab (T) has shown clinical benefit in HER2 overexpressing cases. Nevertheless, literature published so far is scant regarding trastuzumab combination with second-line P/R. We report here our experience in the use of maintenance trastuzumab in combination with P/R in HER2 overexpressing G/GEJ adenocarcinoma patients. Correlative HER2 positive G/GEJ patients with progression of disease as per RECIST criteria after first-line treatment based on platinum, fluoropyrimidines, and trastuzumab were included in this study and treated between January 2017 and December 2019. Statistical analysis was performed according to non-parametrical tests based on the Mann-Whitney U test to compare progression-free survival (PFS) between both groups. Overall Response Rates were evaluated according to Fisher’s exact test. A total of 12 patients were included in this analysis. 8 of them (66,6%), underwent maintenance T together with P/R after confirmed progression to first-line. The remaining cases (n=4; 33,3%) were treated according to with to SOC based on P/R without T. ORR in the T+P/R group was 62.5% (n=5) reaching a disease control rate up to (DCR) of 87% (n=7) in contrast to SOC in which no response was observed showing a DCR of 50% (n=2). Statistical comparison using Fisher’s exact test did not reveal statistical significance (p=0.07) likely due to insufficient sample size. Moreover, median PFS was 5.5 months among patients receiving T+P/R and 4.5 months in the P/R group. No significant differences were found between groups (Mann Whitney U test p=0.55). In terms of toxicity, maintenance trastuzumab did not demonstrate treatment-related increased cardiotoxicity. The overall incidence of grade 3 or 4 adverse events according to the CTCAE 5.0 was 25%, 2 cases in the P/R group (1 bleeding, 1 nonfebrile neutropenia) and 1 in the combination with trastuzumab (thrombosis). Combination of trastuzumab and SOC P/R could offer benefits in terms of response and progression-free survival, although no statistical differences were seen probably as a result of our limited sample size. Nevertheless, combination therapy does neither seem to add more toxicity than that expected with the SOC based on P/R alone, nor does it appear to have remarkable cumulative cardiovascular toxicity in our series. Despite our limitations, in patients with HER2 overexpressing GEJ adenocarcinoma, maintenance trastuzumab with second-line P/R until further progression could be a feasible option in patients with good performance status who are fit for combined therapy.