808MO - Paclitaxel with or without pazopanib in ovarian cancer patients with relapse during bevacizumab maintenance therapy: The GINECO randomized phase II TAPAZ study

Background

Anti-angiogenic rechallenge combining bevacizumab and chemotherapy is efficient among relapse Ovarian Cancer (OC) patients (pts). However few data are available with tyrosine kinase inhibitors if progression during bevacizumab maintenance.

Methods

TAPAZ is a French randomized (2:1) phase II trial including recurrent OC pts during the first year of bevacizumab maintenance therapy in 1^st or 2^nd line, comparing weekly paclitaxel 65 mg/m² with pazopanib 600 to 800 mg daily (PP arm) to weekly paclitaxel 80mg/m² (P arm). Primary endpoint was Progression-Free-Survival (PFS). Main secondary endpoints were Overall Survival (OS), safety, pharmacokinetic, and Quality of Life (QoL).

Results

116 pts were enrolled, 79 in PP and 37 in P arms. Median age was 65 y [42-85], relapse < 6months (mo) 70%, serous histology 88%, FIGO III/IV 98%. With a median follow-up of 12.8 mo [1-47], median PFS was 4.6 mo [3.9-6.1] in PP arm vs 5.5 mo [4.8-7.3] in P arm (p=0.6) and OS 13.5 vs 12.8 mo, respectively (p=0.77). Weekly median dose of Paclitaxel was 65 mg/m² in PP arm and 80 mg/m² in P arm. 14% of pts in PP arm received 800 mg of daily Pazopanib. 81% of pts in P arm stopped treatment because of progression vs 66% (p =0.09). G3/4 toxicities were more frequent in PP arm (87% vs 70%, p=0.03). Treatments discontinuation for toxicity was 47% in PP arm (including the 2 drugs in 19%) vs 12% in P arm (p<0.001). In PP arm, discontinuation was mainly due to digestive (31%), vascular (thrombosis, HBP) (28%) and hematologic (17%) disorders, with 3 sepsis and 2 toxic deaths (pulmonary embolism and digestive perforation). More significant deterioration of global QoL and diarrhea at 4 mo was reported in PP arm (mean change: -9 [-14; -3], p=0.003 and 11 [2-19], p=0.01, respectively). In PP arm, PFS and OS were not related to pazopanib plasma exposure at cycle 1 (p=0.7 and 0.5) but pts experiencing vomiting at cycle 1 had higher pazopanib exposure (p=0.01).

Conclusions

Addition of pazopanib to paclitaxel in recurrent OC pts progressing during bevacizumab maintenance is not superior to paclitaxel. It increases toxicity and compromises chemotherapy efficacy leading to more frequent early treatment discontinuations.

Clinical trial identification

EudraCT 2014-003843-37; NCT02383251 (First posted: March 2015, Last Update: January 2020).

Editorial acknowledgement

Legal entity responsible for the study

ARCAGY-GINECO.

Funding

ARCAGY-GINECO, Novartis.

Disclosure

F. Joly Lobbedez: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Astellas; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (institution), Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy: Clovis. M. Fabbro: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GSK. D. Berton: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro; Travel/Accommodation/Expenses, ESMO: Pfizer; Travel/Accommodation/Expenses, ESCO: PharmaMar. A. Anota: Honoraria (self): Roche; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: Sandoz; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Pfizer/Hospira; Travel/Accommodation/Expenses: Novartis. A. Puszkiel: Full/Part-time employment: Hospices Civils de Lyon, Groupement Hospitalier Sud. A. Floquet: Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: MSD; Travel/Accommodation/Expenses, Non-remunerated activity/ies: Roche. L. Bengrine Lefevre: Honoraria (institution), Full/Part-time employment: Centre Georges Francois Leclerc (hospital); Advisory/Consultancy: AstraZeneca. B. You: Honoraria (institution): HCL & Université de Lyon; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: GSK; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis; Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: ECS Progastrin; Research grant/Funding (institution): Gineco. A. Lortholary: Honoraria (self): GSK; Honoraria (self): Roche; Honoraria (self): Novartis. D. Spaeth: Honoraria (self): Astra; Travel/Accommodation/Expenses: Pfizer. C. Abdeddaim: Advisory/Consultancy: GSK/Tesaro; Advisory/Consultancy: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck. M-C. Kaminsky-Forrett: Honoraria (self): Tesaro; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: Merck. D. Petran: Travel/Accommodation/Expenses, Congrès, Réunions: Amgen; Travel/Accommodation/Expenses, Congrès, Réunions: Sandoz; Travel/Accommodation/Expenses, Congrès, Réunions: Pfizer; Travel/Accommodation/Expenses, Congrès, Réunions: Ipsen; Travel/Accommodation/Expenses, Congrès, Réunions: Roche; Travel/Accommodation/Expenses, Congrès, Réunions: BMS. P-E. Brachet: Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.