Sir Peter MacCallum Department of Oncology - Research Publications

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    REZOLVE (ANZGOG-1101): A phase 2 trial of intraperitoneal bevacizumab to treat symptomatic ascites in patients with chemotherapy-resistant, epithelial ovarian cancer
    Sjoquist, KM ; Espinoza, D ; Mileshkin, L ; Ananda, S ; Shannon, C ; Yip, S ; Goh, J ; Bowtell, D ; Harrison, M ; Friedlander, ML (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2021-04-24)
    BACKGROUND: The primary aim of this study was to evaluate the activity of intraperitoneal bevacizumab (IP-bev) in delaying re-accumulation of malignant ascites in women with chemotherapy-resistant epithelial ovarian cancer (CR-EOC) who have ceased chemotherapy. Secondary outcomes were safety and quality of life. METHODS: Women with CR-EOC and malignant ascites that reaccumulated within 28 days of their last paracentesis (P-1) were administered IP-bev 5 mg/kg following their first therapeutic paracentesis on study (P0). Additional doses of IP-bev were allowed at each subsequent paracentesis (P1, P2, etc) provided the interval from the last dose was 42 days or greater (median time from first to second therapeutic ascitic drainage). RESULTS: 24 participants (median age 67 years [range 38-86]; median 4.5 lines prior systemic treatment [range 1-12]; ECOG performance status of 0 in 1, 1 in 8, and 2-3 in 15) were recruited. The doses of IP-bev administered were 1 in 13 participants, 2 in 5, 3 in 2, 4 in 1, and 5 in 1. The proportion with a TTP of >42 days using competing risk analysis was 77% (95% CI 58-92). Median time from P0 to P1 or death was 48 days (range 8-248). Median paracentesis-free interval (P0-P1 or death) was 4.29-fold (95% CI 2.4-5.8) higher following a first dose of IP-bev compared with the time between paracenteses prior to study entry (P-1-P0). CONCLUSION: IP-bev was safe, active, and warrants further study as a palliative intervention for recurrent ascites in CR-EOC patients receiving best supportive care.
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    Therapeutic options for mucinous ovarian carcinoma
    Gorringe, KL ; Cheasley, D ; Wakefield, MJ ; Ryland, GL ; Allan, PE ; Alsop, K ; Amarasinghe, KC ; Ananda, S ; Bowtell, DDL ; Christie, M ; Chiew, Y-E ; Churchman, M ; DeFazio, A ; Fereday, S ; Gilks, CB ; Gourley, C ; Hadley, AM ; Hendley, J ; Hunter, SM ; Kaufmann, SH ; Kennedy, CJ ; Kobel, M ; Le Page, C ; Li, J ; Lupat, R ; McNally, OM ; McAlpine, JN ; Pyman, J ; Rowley, SM ; Salazar, C ; Saunders, H ; Semple, T ; Stephens, AN ; Thio, N ; Torres, MC ; Traficante, N ; Zethoven, M ; Antill, YC ; Campbell, IG ; Scott, CL (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020-03-01)
    OBJECTIVE: Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents. METHODS: We analyzed gene copy number (n = 191) and DNA sequencing data (n = 184) from primary MOC to evaluate signatures of mismatch repair deficiency and homologous recombination deficiency, and other genetic events. Immunohistochemistry data were collated for ER, CK7, CK20, CDX2, HER2, PAX8 and p16 (n = 117-166). RESULTS: Molecular aberrations noted in MOC that suggest a match with current targeted therapies include amplification of ERBB2 (26.7%) and BRAF mutation (9%). Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutations (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (HRD) may not be effective in MOC, as only 1/191 had a high HRD score. Mismatch repair deficiency was similarly rare (1/184). CONCLUSIONS: Although genetically diverse, MOC has several potential therapeutic targets. Importantly, the lack of response to platinum-based therapy observed clinically corresponds to the lack of a genomic signature associated with HRD, and MOC are thus also unlikely to respond to PARP inhibition.