Abstract
BackgroundPopulation-based predictive factors for the effectiveness of second-line palliative systemic therapy in gastro-oesophageal cancer are not available. This study investigates the predictive value of effectiveness of first-line treatment for second-line treatment outcomes in gastro-oesophageal cancer in a real-world setting. MethodsPatients with metastatic gastro-oesophageal cancer diagnosed in 2010–2017 who were treated with second-line therapy after disease progression on first-line therapy were identified from the Netherlands Cancer Registry. Patients were divided into four groups as per duration of time to treatment failure (TTF) of the first line (0–3, 3–6, 6–9 and >9 months), and the association with overall survival (OS) and second-line TTF was assessed using Kaplan-Meier curves and two-sided multivariable regression models. ResultsMedian OS since the start of the second line of patients (n = 611) with first-line TTF of 0–3, 3–6, 6–9 and >9 months was 4.0, 4.1, 5.5 and 7.1 months, respectively (P < 0.001). Median second-line TTF of patients with first-line TTF of 0–3, 3–6, 6–9 and >9 months was 2.8, 2.4, 3.0 and 4.5 months, respectively (P < 0.001). Patients with first-line TTF of >9 months showed a longer OS than patients with first-line TTF of 0–3 months (adjusted hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.46–2.47), 3–6 months (adjusted HR 1.88; 95% CI 1.47–2.39) and 6–9 months (adjusted HR 1.31; 95% CI 1.04–1.65). Results for second-line TTF were similar. ConclusionsThis study shows a positive correlation between effectiveness of first-line therapy and outcomes of second-line therapy in gastro-oesophageal cancer. Physicians should take duration of the first line into account when considering second-line palliative systemic therapy.
Highlights
The primary tumour was located in the oesophagus in 50%, at the gastro-oesophageal junction in 20%, and in the stomach in 29%, with the majority being adenocarcinomas (93%) of the intestinal type (45%)
human epidermal growth factor receptor 2 (HER2) status was negative in 56% and unknown in 23% of patients with adenocarcinoma
This is the first relatively large population-based study in patients with gastric or oesophageal cancer to show a positive association between effectiveness of first-line palliative systemic therapy and effectiveness of second-line palliative systemic therapy
Summary
Palliative systemic therapy can increase both quality of life and survival compared with best supportive care in patients with metastatic gastro-oesophageal cancer [1]. Three lines of palliative systemic treatment have been approved [2e4]. After progression on first-line therapy, which is usually a combination of a fluoropyrimidine and a platinum compound, second-line treatment with taxane- or irinotecan-based regimens may render better survival and quality of life outcomes than best supportive care [5e9]. Since 2016, the combination of paclitaxel and ramucirumab, a monoclonal antibody against vascular endothelial growth factor receptor, has been approved for second-line palliative systemic therapy and further improved the survival compared with taxane monotherapy [7,10]. Third-line treatment with trifluridine/tipiracil showed better survival in patients with gastric cancer than best supportive care [11]
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