OCCC is a rare entity linked to good prognosis at early stages but chemoresistance and poor survival in advanced setting. Molecular heterogeneity is common in OCCC, with PI3K/mTOR pathway alterations as most common drivers.
Consecutive series of 75 patients (pts) with OCCC treated in VHH/VHIO from 2000 to 2016. Objective: to study outcomes with standard therapy (progression-free survival [PFS], overall survival [OS]) and treatment selection in a chemotherapy (ChT) resistant setting based on molecular profiling performed in house (targeted NGS panel).
Median age was 55 years (y), FIGO (2014) stage I 51%, II 11%, III 33%, IV 5%. Primary surgery was performed in 92% achieving optimal cytoreduction in 86%. All pts received first-line of platinum (Pt)-based ChT. With a median follow-up of 9.5 y, 50.6% pts relapsed (I 34.2%, II 62.5%, III 68%, IV 50%), median OS was 11.2 y (CI95%: 6-NR). Factors significantly associated with relapse and death in univariate Cox models were ECOG performance status and stage at diagnosis (p < 0.001). At 1st and 2nd relapse, 58 and 50% remained Pt-sensitive, respectively. Median PFS with therapies after 1st relapse in a Pt-sensitive setting (91% Pt combos) was 12.6 months (m) (CI95% 9.5-25.4) and in Pt-resistant setting (69% non-platinum ChT) 3 m (2.5-NA). In total, 18 pts (24%) had genomic profiling (7 PIK3CA mut, 1 BRCA1 mut, 1 MSH6 mut), and 16 pts (21%) received experimental agents after 1st relapse (8 antiangiogenic, 4 targeted or immunotherapy unmatched, 4 targeted matched [3 PI3K inh and 1 PARP inh]). Median PFS was 4.8, 5.6 and 9.6 m respectively. When compared to non-Pt ChT in a Pt-resistant setting increased PFS was found with matched targeted agents (HR = 0.26, CI95% 0.1-1).
As reported in the literature, in our cohort, OCCC are more frequent diagnosed at early stages having a better prognosis. In the relapse setting Pt sensibility and Pt-based ChT imply better outcomes. However, in the Pt-resistant setting targeted therapies result in better PFS compared to ChT. Molecular profiling allows to select matched agents which may improve outcomes in this poor prognosis population. Further research in molecular characterization and matched targeted therapy is an unmet need.
Clinical trial identification
Legal entity responsible for the study
Vall d'Hebron Institute of Oncology (VHIO).
Has not received any funding.
All authors have declared no conflicts of interest.