In metastatic breast cancer, bevacizumab (Bev)-based treatment beyond progression (TBP) has been found a valid option, whereas TBP with Bev in tuboovarian carcinoma (TOC) has not been intensively investigated so far. This retrospective study sought to investigate the feasibility and effectiveness of multiple lines of Bev-based systemic therapy (Tx) in patients (pts) with recurrent TOC.
From our database, a total of 90 pts with recurrent TOC (45 with platinum-sensitive or platinum-resistant disease each) receiving at least one line of Bev-based Tx were identified. 37 (41.1%) pts had one, 20 (22.2%) two, 13 (14.4%) three, and 20 had (22.2%) 4-9 lines of Bev. A total of 225 courses of Bev-based Tx were administered: 58 (25.8%) as monotherapy (Bev), 63 (28.0%) in combination with conventionally dosed chemotherapy (Bev+cCtx), and 104 (46.2%) in combination with metronomic Ctx (Bev+mCtx). Time to progression (TTP) was calculated from the start of each Bev-based Tx until progression, overall survival was calculated from the start of the first Bev-based Tx until death from any reason or loss to follow-up. Adverse effects in regard to Bev were scored according to CTCAE vs 4.02.
Most frequent side effects of Bev were proteinuria occurring in 50%, hypertension in 41%, gastrointestinal toxicity in 31%, and infection in 17% of treatments. However, G3-4 toxicities were rare with hypertensive crisis in 2.2%, bowel obstruction in 0.9%, bowel perforation in 0.9%, nephrotic syndrome in 0.4% and infection seen in 1.3% of treatments. Both TTP and OS did not differ between different types of Tx. TTP: Bev, 5.4 months (mts); Btsv+cCtx, 6.1 mts; Bev+mCtx, 6.3 mts. OS: Bev, 28.6 mts, Bev+cCtx, 31 mts; B+mCtx, 21.4 mts. TTP for platinum-resistant vs platinum-sensitive pts was 4.5 and 7.6 mts (p=NS) and OS was 20.1 vs 12.2 mts (p = 0.044). TTP was comparable between one and multiple lines of Bev: one line, 6.6 mts; two lines, 6.3 mts, three lines 5.9 mts, and 4-9 lines 3.7 mts (p = 0.130). However, OS increased significantly with the number of Bev-based lines of Tx: one line, 8.8 mts; two lines, 16.8 mts; three lines 25.4 mts; 4-9 lines, 36.6 mts (p = 0.0001).
Our results demonstrate that retreatment with Bev can be safely given to pts with recurrent TOC in the clinical routine. The incidence of severe side effects was generally low and did not increase by the line of Bev-based Tx. However, the number of Bev-based lines had a significant impact on overall survival. Thus, rechallenge with Bev may be a valuable option in the treatment of recurrent TOC.
Clinical trial identification
Legal entity responsible for the study
Christian M. Kurbacher
C.M. Kurbacher: Author received honoraria from Roche, Amgen, Novartis, Teva Oncology, Riemser. All other authors have declared no conflicts of interest.