The Impact on Outcome by Adding Bevacizumab to Standard Induction Chemotherapy Prior to Mesothelioma Surgery: A Retrospective Single Center Analysis

Our plain-English summary of The Impact on Outcome by Adding Bevacizumab to Standard Induction Chemotherapy Prior to Mesothelioma Surgery: A Retrospective Single Center Analysis, by O. Lauk, K. Bruestle, T. Neuer, et al (Frontiers in Oncology, 2020).

The study

• Authors: O. Lauk, K. Bruestle, T. Neuer, B. Battilana, T.D.L. Nguyen, T. Frauenfelder, R. Stahel, W. Weder, A. Curioni-Fontecedro, I. Opitz
• Journal: Frontiers in Oncology
• Published: 2020;10:588563
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Adding bevacizumab, an anti-Vascular Endothelial Growth Factor (VEGF), to platinum-based chemotherapy/pemetrexed in 1st line treatment of advanced malignant pleural mesothelioma (MPM), significantly improved overall survival. However, increased high grade bleeding after operation was reported in patients with colorectal cancer who previously received bevacizumab. In the present analysis, we assessed for the first time the impact of adding bevacizumab to induction chemotherapy prior to surgery for mesothelioma patients.

Methods: Two hundred twenty-seven MPM patients, intended to be treated with induction chemotherapy followed by surgery at the University Hospital of Zurich between 2002 and December 2018, were included in the present analysis. After propensity score matching for gender, histology and age (1:3 ratio), data from 88 patients were analyzed. Sixty-six patients underwent induction chemotherapy (with cis-/carboplatin and pemetrexed: control group) alone and 22 patients underwent induction chemotherapy with the addition of bevacizumab (bevacizumab group) prior macroscopic complete resection (MCR). Perioperative and long-term outcome variables were analyzed.

Results: Patients undergoing combination treatment with bevacizumab had a significantly better response than with chemotherapy alone as assessed by modified RECIST (p=0.046). Intraoperative complications in the bevacizumab group (one patient), or in the control group (three patients) were not related to intraoperative bleeding. Postoperative transfusion of blood products occurred in a larger amount in the control group than in the bevacizumab group (p=0.047). Overall survival was not statistically different between both groups.

Conclusion: These initial data demonstrate that MCR can be performed safely after triple induction chemotherapy with bevacizumab without increased intra- and postoperative bleeding complications. Response rates were significantly improved by the addition of bevacizumab.

Copyright © 2020 Lauk, Bruestle, Neuer, Battilana, Nguyen, Frauenfelder, Stahel, Weder, Curioni-Fontecedro and Opitz.

In plain English

This retrospective study from University Hospital Zurich examined patients with malignant pleural mesothelioma who were given chemotherapy before surgery between 2002 and 2018. After matching for age, gender and tumor type, the authors compared 22 patients whose chemotherapy (cisplatin or carboplatin with pemetrexed) included bevacizumab with 66 who had chemotherapy alone. On scans after this chemotherapy, no bevacizumab patient's tumor had progressed, against 15 (22.7%) control patients, and overall response was better with bevacizumab (p=0.046). Four patients had complications during surgery, none from bleeding. Blood products after surgery went to 95.5% of the bevacizumab group and 68.2% of the control group (p=0.047), although the abstract says a larger amount went to the control group. Pulmonary embolism occurred in six patients in each group (27.3% versus 9.1%, p=0.09). Median overall survival was 22.4 months with bevacizumab (95% CI 13.5 to not applicable) and 23 months without (95% CI 17.3 to 33.5), p=0.55, not statistically different. The authors concluded that surgery can still be performed safely if appropriate time intervals are respected. They noted the small, non-randomized sample and called for larger studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective observational single-center study with 1:3 propensity score matching
• Who was studied: Patients with malignant pleural mesothelioma at University Hospital Zurich, 2002–2018, who were intended to receive induction chemotherapy followed by surgery (n=227). 66 were excluded, 161 were matched, and 88 were analyzed: 66 in the control group and 22 in the bevacizumab group.
• Exposure: Not asbestos exposure. The study compared two treatments before surgery: induction chemotherapy with cisplatin or carboplatin plus pemetrexed, either with bevacizumab added (22 patients) or without it (66 patients). The last cycle before surgery was given without bevacizumab.
• Main results:
  • Tumor progression after induction chemotherapy, assessed by mRECIST on restaging scans: no patients in the bevacizumab group versus 15 patients (22.7%) in the control group.
  • Overall response was better in the bevacizumab group, p=0.046.
  • Intraoperative complications: 3 patients in the control group and 1 in the bevacizumab group, none due to bleeding.
  • Postoperative blood products: 68.2% of the control group versus 21 patients (95.5%) of the bevacizumab group (p=0.047).
  • Pulmonary embolism: six patients in each group, which was 9.1% of the control group and 27.3% of the bevacizumab group (p=0.09).
  • 30-day mortality: 1 (1.5%) in the control group and 1 (4.5%) in the bevacizumab group, not statistically different. 90-day mortality: 4 (6.1%) in the control group and 1 (4.5%) in the bevacizumab group.
  • Median overall survival: 23 months (95% CI 17.3 to 33.5) in the control group and 22.4 months (95% CI 13.5 to not applicable) in the bevacizumab group; p=0.55.
  • Median progression-free survival: 11.5 months (95% CI 11.1 to 14.5) in the control group and 11.4 months (95% CI 10.1 to 18.2) in the bevacizumab group; no statistical difference.
  • No patient showed a major pathological response, and all surgical specimens still contained living tumor tissue under the microscope.
• The authors' conclusion: The authors concluded that, although increased bleeding risk is a known side effect of bevacizumab, mesothelioma surgery can still be performed safely if appropriate time intervals are respected, and that the approach warrants investigation in a larger number of patients.
• Limitations the authors state:
  • The study was retrospective, even though propensity score matching was used.
  • The small sample size and the lack of randomization prevent firm conclusions about bleeding complications.
  • Outcomes may have been influenced by potential confounders.
  • Patient management may have improved over the long study period, including a shift from extrapleural pneumonectomy to (extended) pleurectomy/decortication, at the same time that bevacizumab was given in the later period.
  • No adjustment was made for multiple testing, so p values should be read as descriptive.

Topics

Medical terms in this study, explained in our Lexicon: Bevacizumab, Chemotherapy, Mesothelioma, Pemetrexed (Alimta), Pleural Mesothelioma, Overall Survival, Colorectal Cancer, Histology.

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