Quality of life, vascular endothelial growth factor inhibition, and survival outcomes with combination oral metronomic therapy in platinum refractory epithelial ovarian carcinoma: Results from a randomized study.

Abstract

6048 Background: Patients with recurrent and refractory epithelial ovarian cancer (EOC) have dismal outcomes. We evaluated a combination of oral metronomic therapy in platinum refractory EOC vis-à-vis angiogenic marker expression and its impact on patient reported outcomes. Methods: Between October 2017 and September 2019, 75 patients were randomized to receive etoposide (VP-16) (50 mg daily for 14 days) cyclophosphamide (50 mg daily for 28 days) (Arm A, n = 38) or etoposide (VP-16) (50 mg daily for 14 days) cyclophosphamide (50 mg daily for 28 days) and pazopanib (400 mg daily 28 days) every 28 days (Arm B, n = 37). Eligibility criteria included histopathological diagnosis of EOC, platinum refractory disease and ECOG performance status 0-2. Primary endpoint was serological progression free survival (PFS) as defined by Rustin criteria. Quality of Life (QoL) (evaluated using the EORTC QLQC30 and OV 28 questionnaires) and serum vascular endothelial growth factor (VEGF) were ascertained at baseline and after 3rd and 6th cycle. Intention to treat analysis was done. Results: Baseline characteristics were well matched in 2 arms. At a median follow up 14.4 months (95% CI 13.2-15.7), the median serological PFS is better for patients in Arm B 5.1 months (95%CI 3.13-10.33) compared to 3.4 months (95%CI 3-6.53) in arm A ( P= 0.045). Median overall survival (OS) is not reached in arm B versus 11.2 months (95%CI 5.66-NR) in arm A (P= 0.032). Disease progression was seen in 42.1% (n = 16) in Arm A versus 40.5 %(n = 15) in arm B ( P= 0.40). Sixteen patients are maintaining response. Mucositis (29.7% n = 11) and fatigue (13.5%, n = 5) were more in the pazopanib-containing arm ( P= 0.36). Serum VEGF demonstrated significant decline with subsequent cycles of therapy {median values (range): Arm A, baseline; 466.0 pg/mL(123.9-1930) vs. 6 cycles; 92.05pg/ mL(42.34-279.5) P< 0.0001; Arm B, baseline; 382.0 pg/mL(49.44-2054.0) vs 6 cycles; 119.7 pg/mL(18.20-367.5) P= 0.013} without any difference between the two arms ( P= 0.18). QoL symptom scales in both QLQC 30 and OV 28 questionnaires indicated small but significant improvement in pazopanib arm ( P= 0.02) without differences in global (p = 0.96) and physical functioning scales. ( P= 0.68). Conclusions: Addition of pazopanib to etoposide and cyclophosphamide resulted in improvement in serological PFS and OS with a well-tolerated toxicity profile and modest improvement in QoL.Serum VEGF expression requires validation in a larger cohort. Clinical trial information: CTRI/2017/10/010219.