Heterogeneity of first-line palliative systemic treatment in synchronous metastatic esophagogastric cancer patients: A real-world evidence study

Abstract

The optimal first-line palliative systemic treatment strategy for metastatic esophagogastric cancer is not well defined. The aim of our study was to explore real-world use of first-line systemic treatment in esophagogastric cancer and assess the effect of treatment strategy on overall survival (OS), time to failure (TTF) of first-line treatment and toxicity. We selected synchronous metastatic esophagogastric cancer patients treated with systemic therapy (2010-2016) from the nationwide Netherlands Cancer Registry (n = 2,204). Systemic treatment strategies were divided into monotherapy, doublet and triplet chemotherapy, and trastuzumab-containing regimens. Data on OS were available for all patients, on TTF for patients diagnosed from 2010 to 2015 (n = 1,700), and on toxicity for patients diagnosed from 2010 to 2014 (n = 1,221). OS and TTF were analyzed using multivariable Cox regression, with adjustment for relevant tumor and patient characteristics. Up to 45 different systemic treatment regimens were found to be administered, with a median TTF of 4.6 and OS of 7.5 months. Most patients (45%) were treated with doublet chemotherapy; 34% received triplets, 10% monotherapy and 10% a trastuzumab-containing regimen. The highest median OS was found in patients receiving a trastuzumab-containing regimen (11.9 months). Triplet chemotherapy showed equal survival rates compared to doublets (OS: HR 0.92, 95%CI 0.83-1.02; TTF: HR 0.92, 95%CI 0.82-1.04) but significantly more grade 3-5 toxicity than doublets (33% vs. 21%, respectively). In conclusion, heterogeneity of first-line palliative systemic treatment in metastatic esophagogastric cancer patients is striking. Based on our data, doublet chemotherapy is the preferred treatment strategy because of similar survival and less toxicity compared to triplets.

Keywords: drug therapy; esophageal neoplasms; gastric neoplasms; palliative treatment.

Figure 1

Flowchart of patient selection.

Figure 2

Overall survival of synchronous metastatic esophagogastric cancer patients. Kaplan–Meier curves displaying overall survival in patients treated with one, two or three chemotherapeutic agents (monotherapy, doublet and triplet, respectively) and in patients treated with a trastuzumab‐containing regimen, diagnosed between 2010 and 2016 (n = 1,981). Survival curve of patients treated with a regimen containing (nontrastuzumab) targeted therapy (n = 23) is not displayed.

Figure 3

Time to failure of first‐line therapy in synchronous metastatic esophagogastric cancer patients. Kaplan–Meier curves displaying time to failure of first‐line treatment in patients treated with one, two or three chemotherapeutic agents (monotherapy, doublet and triplet, respectively) and in patients treated with a trastuzumab‐containing regimen, diagnosed between 2010 and 2015 (n = 1,680). Survival curve of patients treated with a regimen containing (nontrastuzumab) targeted therapy (n = 20) is not displayed.