Analysis on the efficacy and safety of chemotherapy combined with or without bevacizumab after CRS+HIPEC in patients with malignant peritoneal mesothelioma: a single-center retrospective study

TL;DR

This study explores whether adding bevacizumab to chemotherapy after surgery improves survival in patients with malignant peritoneal mesothelioma.

Contribution

The study provides new evidence on the efficacy and safety of bevacizumab combined with chemotherapy after CRS+HIPEC in MPM patients.

Findings

Combining bevacizumab with chemotherapy significantly improved overall and disease-free survival in MPM patients.

Adverse events were mostly mild, with few cases of severe side effects in both treatment groups.

Postoperative chemotherapy with bevacizumab was identified as an independent prognostic factor for better survival.

Abstract

To investigate the efficacy and safety of pemetrexed/platinum-based chemotherapy combined with or without bevacizumab after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of patients with malignant peritoneal mesothelioma (MPM).

A retrospective non-randomized study was performed on 205 MPM patients treated with CRS+HIPEC at our institution. A total of 97 eligible patients were analyzed: 58 patients who received postoperative chemotherapy combined with bevacizumab (C&B) and 39 patients who received chemotherapy alone (C) were divided into a study group and a control group, respectively. The patients were also divided into the bevacizumab-exposed subgroup and the bevacizumab-unexposed subgroup based on whether they had a history of bevacizumab infusion. Clinicopathological data and follow-up information were statistically analyzed. Independent prognostic factors were identified via survival analysis, and the safety of combination therapy was assessed via adverse event analysis.

As of the follow-up cutoff date of July 1, 2025, in both the subgroups with and without a history of bevacizumab infusion, there was no statistically significant difference between the control and study groups in baseline pathological characteristic parameters (p > 0.05). Survival analysis revealed that in the subgroup of patients with a history of bevacizumab infusion, the difference in median overall survival (mOS) between the control and study groups was statistically significant (31.9 months vs. NR; p = 0.031), and the difference in median disease-free survival (mDFS) between the control and study groups was statistically significant (12.5 months vs. NR; p = 0.001); in the subgroup of patients without a history of bevacizumab infusion, the difference in mOS between the control and study groups was also statistically significant (20.5 months vs. NR; p = 0.001), and the difference in mDFS between the control and study groups was statistically significant (13.2 vs. 36.2 months; p = 0.001). The Cox regression model found that postoperative C&B was an independent prognostic factor (p = 0.009, HR = 0.081, 95% CI: 0.012–0.526) in the subgroup with a history of bevacizumab infusion, and the Ki-67 index (p = 0.043, HR = 2.563, 95% CI: 1.029–6.386) and postoperative C&B were independent prognostic factors (p = 0.01, HR = 0.086, 95% CI: 0.032–0.232) in the subgroup with no bevacizumab treatment history. A total of 101 cases of grade 1~2 adverse events in the study group were revealed via adverse event analysis, with common events including nausea/vomiting, fatigue, leukopenia/neutropenia, thrombocytopenia, anemia, abnormal liver function, hypertension, and proteinuria. There were four cases with grade 3 adverse events, mainly leukopenia/neutropenia, hypertension, and proteinuria. In the control group, there were 84 cases of grade 1~2 adverse events, and three cases of grade 3 adverse events were observed.

Our exploratory findings suggest that bevacizumab combined with pemetrexed/platinum-based chemotherapy may be a therapeutic option for MPM patients after CRS+HIPEC; however, a prospective, randomized controlled clinical study is needed to validate our findings.

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