Clinical characteristics of relapsed ovarian cancer patients with striking response to the bevacizumab at first relapse

Abstract

Background: Ovarian cancer is fifth leading cause of the cancer related death in women. Platin based doublet regimen plus bevacizumab is standard treatment in relapse. The primary aim of this study is to define clinicopathological characteristics of the relapsed ovarian cancer who derived unexpectedly long benefit from bevacizumab treatment. Methods: Total number of 106 patients with relapsed ovarian cancer and treated with bevacizumab (bevacizumab is not reimbursed as a part of adjuvant treatment in Turkey) on their first relapse were included. For the purpose of the study, the patients were placed into two groups, Group A and B, selected on the basis of the rate of PFS 1 (time between first day of adjuvant chemotherapy and first radiological progression) to PFS 2 (time between first day of second line treatment and second radiological progression). The patients included into Group A if PFS 1 greater than PFS 2 and Group B vice versa. Results: Group A and B were consisted of 67 (63%) and 39 (37%) patients. At a median follow-up of 32.1 months (5.3-110.8), 56 (52.8%) patients were died. Significant number of patients (78.4%) treated with primary surgery without neoadjuvant treatment and 59 (57.8%) out of the 102 patients had debulking surgery when their cancer relapsed. PFS 1 and 2 were estimated as 16.5 mo (14.1-18.9) vs. 13.7 mo (9.9-17.5) and 13.4 mo (8.0-18.6) vs. 29.7 mo (21.5-38.0) in group A and B, respectively (p < 0.001 and p < 0.001). Only parameter that show significant difference between groups was the rate of platin resistant patients; Group A: 13 (19.4%) out of 67 patients vs. Group B: 15 (38.6%) out of 39 patients with ap value of 0.041. Binary logistic regression indicates PFS1 is significant inverse predictor (shorter PFS-1 means greater chance of being in group B) of entering Group B [Chi-Square = 16.5, df = 6 and p = 0.011 (< 0.05)]. PFS1 is significant at the 5% level [ PFS1 wald = 4.33,p = 0.038 (p < 0.05)]. In multivariate analysis, cox-regression proportional hazard, cytoreductive surgery at second relapse (yes or no) (p: 0.028; HR: 0.3, 0.02-0.7, 95% CI) showed significant effect on PFS-2. On the other hand, platin resistance (< 6 mos; yes or no) (p: 0.04; HR: 4.0, 1.1-14.4, 95% CI) and secondary surgery outcome (no visible vs. visible) (p: 0.003; HR: 0.2, 0.07-0.58, 95% CI) showed significant effect on OS. Bevacizumab related adverse effects with greater than grad 3 detected in 13 (15%) and 10 (25%) in group A and B (p: 0.77). Conclusions: Our findings indicate that bevacizumab produced strikingly high PFS (over 24 months) in significant portion of relapsed ovarian cancer patients whom were mostly platin resistant cases with short PFS-1. This gain specifically achieved in patients who had aggressive secondary surgery with no-visible surgical outcome.