Ovarian SCT tend to respond poorly to chemotherapy (CT). We explored the efficacy of wP with or w/o bev in a randomized 1:1 phase II trial in patients (pts) with relapse who were not candidate to surgery & after > 1 line of platinum based CT.
Primary endpoint is the PFS rate at 6 months (PFR-6). Pts in the wP arm were allowed to receive bev alone at progression. A Bayesian approach allowed continuous monitoring PFR-6 with sequential analyses planned every 20 pts to allow early stopping for efficacy. wP+Bev will be considered interesting if the probability is > 0.9 to show that the estimated PFR-6 in wP+Bev is higher than in wP arm.
From 02/13 to 10/16, 60 pts with SCT (52 AGCT (Adult Granulosa cell tumor), 2 SLT (Sertoli Leydig tumor), 6 other) were randomized. All pts had recurrent disease and were previously treated with CT (47 pts received ≤2 lines). Baseline characteristics were well balanced between the 2 arms. 17 pts (28%) received prior hormonal therapy. Platinum-free interval (PFI) was ≥ 12 months in 21 pts (66%) and 22 (79%) in the wP and wP +bev group, respectively. The PFR-6 [95% CI] was 71% [55%; 84%] vs 72% [55%; 87%] in wP arm (arm A) and wP+bev (arm B). Median PFS were 14.7 and 14.9 months, in arm A and B respectively. In wP arm 50% of pts received bev alone at cross over, with median PFS of 7.3 months. Median TFST were 28.5, 33.6 and 33.6 months, in arm A + cross over bev, arm A w/o crossover and arm B respectively. Most frequent AE (all grade) were: hypertension in 78% of pts wP vs 93% of pts wP+Bev, fatigue (63% vs 78%), neuropathy (56% vs 74%), proteinuria (13% vs 63%), bleeding (16% vs 59%), alopecia (34% vs 56%), vomiting (16% vs 7%). Grade 3/4 AEs were reported in 10 arm wP vs 12 pts in arm wP+Bev.Table: 934O
A randomized trial is feasible in rare cancer with a strong international collaboration. wP confirmed as active drug in SCT. Bev added to wP tends to increase ORR compared to wP alone but failed to significantly improve PFR-6 nor PFS in relapsed SCT pts.
Clinical trial identification
Legal entity responsible for the study
Thanks to all the patients and their families, the investigators, study nurses, pharmacists, pathologists and all study team.
Thanks to Roche laboratory for their financial support.
P. Harter: Honoraria: Roche, Astrazeneca, Tesaro; Consulting: Roche, AstraZeneca, Tesaro, Clovis, Pharmamar. I.B. Vergote: Consulting role: GCI Health, Oncoinvent AS, Rocje NV, Genmab A/S, Advaxis Inc, Morphotec Inc, F. Hoffmann-La Roche Ltd, Cerulean Pharma Inc, Novocure GMBH, AstraZeneca LP, Mateon Therapeutics Inc, Immunogen Inc, Eli Lilly benelux NV, Amgen INc, Theradex Europe Limited, Pfizer Inc, Debiopharma International SA, Vifor Pharma Belgie NV, Novartis Pharma AG, MSD Belgium BVBA, Oxigene Inc, Janssen-Cilag, Nektar Therapeutics, Bayer Pharma AG; Grant: Amgen, Roche; Travel accomodations: Tesaro, Theradex, Elsevier. K. Fujiwara: Honoraria: Chugai, Roche. L. Gladieff: Honoraria: AstraZeneca, Tesaro, Clovis, Roche; Travel accommodations: Roche, Pharmamar. H-J. Lueck: Honoraria: Tesaro, Roche, Amgen, AstraZeneca; Consulting: Tesaro, Roche, Pfizer, Novartis; Speakers' bureau: Roche, Novartis, Pfizer, Amgen; Travel accommodations: AstraZeneca, Tesaro. A. Floquet: Travel accommodations: Roche. A. Schnelzer: Consulting: Roche S. Pignata: Honoraria, Consulting, Travel accommodations: Roche. F. Selle: Consulting: MSD, Roche, AstraZeneca, Tesaro; Travel accommodations: MSD, Roche. J. Sehouli: Honoraria: Roche, AstraZeneca, Tesaro, Pharmamar; Consulting: Novartis, Clovis, Roche, AstraZeneca, Tesaro; Research fundings: Amgen, Novartis, Lilly, Bayer. G. Mangili: Speakers' bureau: Astrazeneca; Research fundings: Ipsen; Travel accommodations: Roche, PharmaMar. P. Pautier: Consulting role: Roche, Tesaro, AstraZeneca, Lilly. U. De Giorgi: Honoraria: BMS, AstraZeneca, Sanofi, Pfizer, Ipsen. P-E. Heudel: Consulting role: AstreZeneca, Pfizer, Novartis; Research fundings: AstrasZeneca; Travel and accommodation: Pfizer, Novartis. All other authors have declared no conflicts of interest.