Survival Outcomes and Prognostic Factors in Metastatic Unresectable Appendiceal Adenocarcinoma Treated with Palliative Systemic Chemotherapy: A 10-Year Retrospective Analysis from Australia

TL;DR

This study analyzed chemotherapy outcomes for advanced appendiceal cancer, finding fluoropyrimidine-based regimens effective and highlighting the role of molecular testing.

Contribution

The study provides real-world evidence on chemotherapy efficacy and identifies KRAS mutations as relevant for targeted therapy in appendiceal adenocarcinoma.

Findings

Fluoropyrimidine-based doublet chemotherapy achieved a 39.4% response rate in advanced appendiceal cancer.

KRAS mutations were found in 68.6% of tested patients, suggesting implications for targeted treatment strategies.

Irinotecan-based regimens showed numerically longer survival compared to oxaliplatin-based ones, though not statistically significant.

Abstract

Appendiceal adenocarcinoma is a rare cancer, and there is limited evidence to guide systemic treatment for metastatic or unresectable cases. This study evaluated real-world outcomes in patients with advanced appendiceal adenocarcinoma who received palliative chemotherapy. The results support fluoropyrimidine-based doublet chemotherapy as an appropriate and preferred option for patients with high disease burden and aggressive tumor features. Single-agent fluoropyrimidine therapy may be a reasonable alternative for frail patients with less aggressive disease. A high incidence of KRAS mutations was observed, which may affect the use of targeted therapies. These findings highlight the need for treatment strategies tailored specifically to appendiceal cancer and suggest that molecular testing may help guide future therapy. This study offers valuable insights to improve care for patients with this rare and understudied disease.

Background: Appendiceal adenocarcinoma is a rare malignancy, and data guiding its systemic treatment in metastatic settings are limited. This study aimed to determine the clinical outcomes, treatment efficacy, biomarkers, and prognostic factors in patients with metastatic or unresectable appendiceal adenocarcinoma receiving palliative chemotherapy. Methods: We retrospectively reviewed patients with metastatic appendiceal adenocarcinoma who received first-line palliative systemic chemotherapy at the Peter MacCallum Cancer Centre between January 2015 and December 2024. Results: Of the 40 patients included, fluoropyrimidine-based doublet regimens were most commonly used (82.5%) in first-line setting, achieving an objective response rate of 39.4%. Median overall survival (OS) was 21.6 months, and median first-line progression-free survival (PFS) was 8.9 months. 22 patients (55.0%) received second-line treatment. Median OS and PFS were 21.6 and 8.9 months, respectively, among patients treated with oxaliplatin-based doublet regimens, and 66.4 and 10.8 months, respectively, among those treated with irinotecan-based doublet regimens. Molecular biomarker testing was performed in 35 patients (87.5%). KRAS and NRAS mutations were identified in 68.6% and 2.9% of tested patients, respectively. Factors associated with poorer OS included male sex, elevated carcinoembryonic antigen levels, and overweight status. Bevacizumab use was not clearly associated with survival. Conclusions: Palliative systemic chemotherapy, particularly fluoropyrimidine-based doublet regimens, appears to be a reasonable and effective treatment option for patients with advanced appendiceal adenocarcinoma. Although this study was underpowered for formal comparison, the numerically longer OS and PFS of irinotecan-based regimens are hypothesis-generating and support further prospective evaluation. Molecular profiling emphasizes the need for personalized targeted therapeutic strategies. The identified prognostic factors may help guide risk stratification and patient counseling for treatment planning.

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