open access: Impact of bevacizumab containing 1st line chemotherapy on recurrent disease in epithelial ovarian cancer

open access
 May 26, 2016

Society Position Statements/White Papers

Impact of bevacizumab containing first line chemotherapy on recurrent disease in epithelial ovarian cancer: A case-control study

Open Access funded by Bill & Melinda Gates Foundation

 

Highlights

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Incorporation of bevacizumab into upfront regimens prolongs PFI in AOC patients.

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However, it is associated with wider presentation of relapse, and lower rate of complete SCS.

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TTP to second line chemotherapy was shorter in women with platinum-sensitive relapse initially treated with bevacizumab.

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Abstract

Objective

To evaluate the timing and pattern of relapse, and duration of response to second line chemotherapy in advanced ovarian cancer (AOC) patients treated with first line carboplatin-paclitaxel chemotherapy with or without bevacizumab.

Patients and methods

This is a case-control study including 222 AOC patients. Seventy-four women treated with first line carboplatin-paclitaxel-bevacizumab chemotherapy (Cases) were matched based on laparoscopic predictive index value, and residual tumor at first surgery with 148 AOC patients treated with carboplatin-paclitaxel. Distribution of pattern of relapse, and response to second line chemotherapy was compared between the two groups. Time to Progression (TTP) for second line chemotherapy was also analyzed for study purpose.

Results

Median platinum-free interval (PFI) was 16 months (range 2–65) in Cases, compared with 9 months (1–83) in Controls (p-value = 0.001). Twenty patients (51.3%) among Cases showed recurrence in multiple anatomic sites, compared with 31 (31.9%) in the Control group (p-value = 0.035). Peritoneal recurrence occurred as diffuse in 30 Cases (96.8%), and 60 Controls (82.2%; p-value = 0.046). Secondary cytoreductive surgery (SCS) was successfully completed in 53.5% of Controls compared to 10.0% of Cases (p-value = 0.016). In women with fully platinum-sensitive relapse, response rate to second line chemotherapy was 85.2% in Controls, compared to 38.4% in Cases (p-value = 0.002). Finally, Cases showed a shorter TTP, compared to Controls (5 months vs 8 months; p-value = 0.041).

Conclusions

Incorporation of bevacizumab into upfront regimens prolongs PFI in AOC patients, but is associated with wider presentation of relapse, lower rate of complete SCS, and shorter TTP to second line chemotherapy in women with platinum-sensitive disease.

1. Introduction

In the past decade, the results of two pivotal randomized phase III clinical trials demonstrated a significant improvement of progression-free survival (PFS), in patients with advanced ovarian cancer (AOC) receiving bevacizumab as part of first line treatment [1] and [2]. Based on these data, in December 2011, Avastin received European regulatory approval for use in combination with carboplatin-paclitaxel as upfront chemotherapy regimen in OC patients with advanced disease.

The observed prolongation of PFS should be considered a relevant therapeutic achievement, since it delays the onset of physical symptoms associated with progressive disease, as well as the need to start a second-line chemotherapy. Furthermore, the prolongation of PFS may in principle increase the chance of response to further platinum-based treatments [3], thus offering a potential long-term benefit.

However, in this encouraging scenario, it is reasonable to hypothesize that the incorporation of bevacizumab into first-line treatment may exert an additional selective pressure on OC cells, with a potentially relevant impact on the natural history of this malignancy. This hypothesis is also supported by recently published retrospective data, which demonstrated a higher rate of lung and pleural recurrence in AOC patients receiving bevacizumab as part of primary treatment [4], thus suggesting that more efforts should be done to definitely clarify how bevacizumab will change the clinical features of OC. Furthermore, despite initial promising results [5] and [6], it remains to be validated an effective signature able to properly identify at diagnosis those AOC patients who may real benefit from first line bevacizumab-based chemotherapy.....