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Purpose: Pazopanib has promising antiangiogenetic activity in solid cancers. The investigator-initiated phase I/II trial evaluated the combination of Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC)., Methods: Patients (≥ 18 years) with first or second recurrence were enrolled in this multicentre open-label trial. Phase I analysed Topotecan 4 mg/m 2 (day 1, 8, 15, ever 28 days) for six cycles to identify the maximum tolerated dose (MTD) of Pazopanib added in a dose-escalating scheme with 400 mg starting dose. The phase II analysed safety and efficacy aspects. For all patients with clinical remission a maintenance with Pazopanib until progression was allowed. This trial is registered with ClinicalTrials.gov, number NCT01600573., Results: Between June 2012 and February 2017, 11 patients were enrolled in the phase I, and 50 patients in the phase II study. The MTD of Pazopanib was determined by 400 mg/daily. Haematological and liver toxicities determined the dose limiting toxicities (DLT) and the most common grade 3-4 adverse events: leucopenia (25%), neutropenia (22%), thrombocytopenia (19%), accumulation of cholestatic (20%) and hepatocellular damage (15%), which often caused dose modifications, but no new life-threatening events. Overall response was 16% and clinical benefit rate 68%. Median progression-free survival (PFS) was 3.5 months (95% CI 2.0-5.0). Due to early progression only 20% of the patients were able to start with maintenance treatment., Conclusion: The combination of pazopanib and weekly topotecan is feasible, resulting in a manageable haematological and liver toxicity, but despite its encouraging response rate, was not associated with a significant survival benefit., (© 2023. The Author(s).)

Purpose: The OVA-YOND study is the first prospective, non-interventional trial designed to evaluate trabectedin (1.1 mg/m 2 ) plus PLD (30 mg/m 2 ) in patients with platinum-sensitive recurrent ovarian cancer (ROC), given according to the marketing authorization in real-life clinical practice across Germany., Methods: Eligible patients were adults with platinum-sensitive ROC, pretreated with ≥ 1 platinum-containing regimen/s. The primary endpoint was to assess safety/tolerability of the combination., Results: Seventy-seven patients with platinum-sensitive relapse from 31 sites were evaluated. Patients received a median of 6 cycles (range 1-21) with 39 patients (50.6%) receiving ≥ 6 cycles. Median treatment duration was 4.2 months (range 0.7-18.8), mostly on an outpatient basis (88.3% of patients). Most common grade 3/4 trabectedin-related adverse events (AEs) were leukopenia (18.2%), neutropenia (15.6%), thrombocytopenia (9.1%), alanine (7.8%) and aspartate aminotransferase (6.5%) increase, and nausea/vomiting (5.2% each). Neutropenia (18.2%), leukopenia (15.6%), thrombocytopenia (10.4%), and nausea/vomiting (5.2% each) were the most frequent grade 3/4 PLD-related AEs. No deaths attributed to drug-related AEs or unexpected AEs occurred. Five patients (6.5%) had a complete response and 19 patients (24.7%) achieved a partial response for an objective response rate of 31.2% with median response duration of 6.25 months. Sixteen patients (20.8%) had disease stabilization for a disease control rate of 51.9%. Median progression-free survival was 6.3 months and median overall survival was 16.4 months., Conclusion: Trabectedin plus PLD confer clinically meaningful benefit to pre-treated patients with platinum-sensitive ROC, being comparable to those previously observed in selected populations from clinical trials and with a manageable safety profile.

Purpose: Triple-negative breast cancer (TNBC) is characterized by a strong heterogeneity with regard to tumour biology as well as in the clinical course of the disease. This study aimed to analyse whether there are any prognostic factors enabling prediction of the clinical outcome in patients with TNBC. Particularly, the impact of Her2-neu score 0 versus Her2-neu score 1 and 2 on survival was investigated., Materials and Methods: We retrospectively studied a cohort of 1013 patients with TNBC, diagnosed at seven hospitals between May 2002 and February 2015. We studied the impact of Her2-neu scores (0 vs. 1 or 2 with negative FISH) on disease-free survival (DFS) and overall survival (OS)., Results: 1013 patients were included in this study. 447 (44.13 %) of them had a T2-4 tumour. A total of 314 (31.00 %) were nodal-positive and 714 (70.48 %) had high-grade tumours. The Her2-neu score of all participating patients was determined. 588 (58.05 %) of them had a Her2-neu score 0, and 425 (41.95 %) had a score of 1 or 2. This study shows that TNBC patients with a Her2-neu score 0 had a significantly poorer outcome regarding DFS (p = 0.0001) and OS (p = 0.0051) compared to a score of 1 or 2. In contrast, grading did not seem to have any prognostic value for women with TNBC., Conclusion: The Her2-neu score 0 might be considered as an innovative prognostic factor for patients with TNBC indicating poor clinical outcome.

Radicality in primary surgical management in gynaecological cancers, especially in ovarian cancer, is the most important factor influencing patient survival. Postoperative residual tumour is one of the most important prognostic factors in ovarian cancer. Radical pelvic and paraaortic lymphadenectomy is recommended in cases of complete resection because of the high incidence of lymph node metastases, especially in the high paraaortic region. A multicenter, prospective randomised study of advanced ovarian cancer by the AGO Ovarian Cancer Study Group is planned to analyse the therapeutic impact of systematic lymphadenectomy in ovarian cancer.