Purpose: Patients with recurrent ovarian clear cell carcinoma (OCCC) have limited effective options due to chemo-resistance. A phase II study was designed to assess the activity of ENMD-2076, an oral multi-target kinase selective against Aurora-A and VEGFR. Experimental design: This multi-center Phase II study included patients with recurrent OCCC who received prior platinum-based chemotherapy. Primary endpoints were objective response and 6-month progression free survival (PFS) rates. Correlative analyses include ARID1A and PTEN expression by immunohistochemistry and gene sequencing with a targeted custom capture next generation sequencing (NGS) panel. Results: 40 patients were enrolled with a median age of 54, 38 were evaluable. ENMD was well tolerated with main related grade 3 toxicities being hypertension (28%), proteinuria (10%) and diarrhea (10%). Best response was partial response for 3 patients (1 unconfirmed) and stable disease for 26 patients. The overall 6-month PFS rate was 22% and differed according to ARID1A expression (ARIDIA -ve vs ARID1A+ve; 33%vs 12%, p=0.023). PTEN positive expression was observed in 20/36 patients and there was no correlation with outcome. Median PFS in patients with PI3KCA wild-type vs PI3KCA-mutated group was 5 versus 3.7 months (p=0.049). Molecular profiling showed variants in PI3KCA (27%), ARID1A (26%) and TP53 (7%). The patient with the longest treatment duration (22 months) was PTEN wild type, diploid PTEN with putative bi-allelic inactivation of ARID1A. Conclusion: Single agent ENMD-2076 did not meet the pre-set bar for efficacy. Loss of ARID1A correlated with better PFS on ENMD-2076 and warrants further investigation as a potential predictive biomarker.
https://ift.tt/2nD1dj1
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου
Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.