A multi-centre review of the efficacy of re-challenge with platinum doublet in patients with oesophagogastric cancer treated with first-line trastuzumab and chemotherapy.

Abstract

367 Background: HER2 amplification or overexpression is seen in 15-20% of metastatic oesophagogastric cancers. The ToGA trial showed an OS benefit for the use trastuzumab with platinum and fluoropyrimidine combination therapy (T-FP) in the first line setting. Second line trials of targeted agents have been disappointing with poor response rates and the current standard of care is paclitaxel and ramucirumab in combination. A recent phase 2 trial showed no OS benefit to continuing trastuzumab with second line chemotherapy but data regarding the efficacy of treatment beyond progression with re-introduction of first line chemotherapy (platinum and fluoropyrimidine) is limited and conflicting. Methods: We conducted a multi-centre retrospective review of patients treated with T-FP in the first-line setting between October 2014 and October 2022 at two large tertiary referral oncology centres in the United Kingdom. Baseline demographic factors and clinical data were collected and compared between responders and non-responders to re-challenge. PFS and OS were estimated using the Kaplan-Meier method. Results: Data was collected for 225 patients in total treated with first-line trastuzumab. We identified 20 patients who had received a re-challenge with FP-T. Best response to first-line treatment was partial response (PR) for 19/20 patients with 1/20 patients with stable disease (SD). There were no differences between baseline demographic factors or tumour pathological features between patients receiving a re-challenge and those treated with chemotherapy alone. The median platinum free interval was 17.8 months. For the re-challenge disease control rate was 75% with an overall response rate of 35% (7 PR, 0 CR). The median number of subsequent trastuzumab cycles was 7, with a median PFS of 6.1 months and median OS of 10 month. Multivariate Cox-regression analysis identified no factors predictive of response in the re-challenge setting. Conclusions: Re-challenge with trastuzumab plus FP chemotherapy is a possible option for patients with relapse. Larger studies will be required to identify predictive biomarkers to identify those patients most likely to benefit. The role of re-assessment of HER2 status at relapse in those receiving re-challenges requires prospective analysis.