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Clinical Trial
. 2023 Aug;149(10):7637-7649.
doi: 10.1007/s00432-023-04647-9. Epub 2023 Mar 31.

Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ)

Radoslav Chekerov #  1 , Tjadina Arndt #  2 , Klaus Pietzner  2 , Ulrich Canzler  3 , Pauline Wimberger  3 , Hans-Georg Strauß  4 , Sven Mahner  5 , Linn Woelber  6 , Nikolaus de Gregorio  7 , Gertraud Stocker  8 , Ekkehard von Abel  9 , Tanja Neunhoeffer  10 , Antje Kristina Belau  11 , Alexander Mustea  12 , Isil Yalinkaya  2 , Elena Ioana Braicu  2 , Rolf Richter  2 , Jalid Sehouli  2 ; NOGGO ovarian cancer study group
Affiliations
Clinical Trial

Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ)

Radoslav Chekerov et al. J Cancer Res Clin Oncol. 2023 Aug.

Abstract

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/m2 (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.

Keywords: Pazopanib; Platinum-resistant ovarian cancer; Topotecan.

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Conflict of interest statement

We declare the following potential conflicts of interest. Employment: none of the authors. Stock or other Ownership: none of the authors. Honoraria: Roche, Eisai, Novartis, MSD, Seagen, GSK, Astra Zeneca, Pfizer, Lumenis, TEVA, pomedicis, Omniamed, PharmaMar, Vifor Pharma, Hexal AG, Lilly (RC, KP, UC, PW, SM, LW, NdG, GS, EvA, AM, EIB, JS). Consulting or advisory role: AstraZeneca, Roche, GSK, Clovis, Eisai, MSD, Seagen, Tesaro, Merck, Novocure, Olympus, Sensor Kinesis, Nykode, Myriad, Daichy (KP, PW, UC, SM, LW, NdG, AM, TN, EIB, JS). Research funding: Roche, GSK, AstraZeneca, Amgen, Novartis, Lilly, Bayer, Medac, Clovis, PharmaMar, Tesaro, Novocure (RC, KP, PW, SM, LW, NdG, GS, AKB, AM, TN, EIB, JS). Patents, Rolayties or Intellectual property: none of the authors. Expert Testimony: none of the authors. Travel, Accomodation, Expenses: Medac, Roche, GSK, AstraZeneca, Lilly (RC, KP, PW, SM, LW, NdG, AM, EIB, JS). Other relationship: none of the authors.

Figures

Fig. 1
Fig. 1
Patient recruitment and treatment within the TOPAZ phase I/II trial
Fig. 2
Fig. 2
Kaplan–Meier plots for Progressive and Overall survival
See this image and copyright information in PMC

References

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