Clinical outcomes and alternative chemotherapy (CT) options in patients (pts) with de novo carboplatin (carbo)-resistant stage III or IV ovarian cancer (CA) based on the drug-induced apoptosis (MiCK) assay.

Abstract

e16525 Background: In order to understand platinum-resistant ovarian CA better, we evaluated the outcomes of pts with in vitro carbo resistance and CT alternatives based on the MiCK assay. Methods: 77 pts with primary stage III or IV ovarian CA previously untreated with CT had a MiCK assay prior to therapy. The MiCK assay was performed as described (J Trans Med 2012; 10:162). Physicians did not receive the results of the assay prior to CT. The time to recurrence in pts treated with standard carbo+paclitaxel CT who had in vitro de novo carbo resistance (carbo KU<1 in the MiCK assay) was compared to time to recurrence in pts treated with carbo+paclitaxel with no in vitro resistance (carbo KU>1) using the log-rank test. The pattern of assay sensitivity to other drugs was analyzed. Results: In pts with de novo carbo resistance in the MiCK assay who were treated with carbo+paclitaxel, the median time to recurrence was only 5.0 months compared to 16 months in pts with carbo sensitivity (p = 0.01). In patients with de novo carbo resistance, 63% of pts were still sensitive (KU>1) to cisplatin in the MiCK assay. For those pts resistant to carbo in the MiCK assay, alternative active CTs were cisplatin 63%, docetaxel 50%, cisplatin+gemcitabine 60%, topotecan 25%, liposomal doxorubicin 20%, etoposide 50%, gemcitabine 17% and cyclophosphamide 50%. The MiCK assay was able to rank individual drugs and combinations with highest drug induced apoptosis for individual patients. Conclusions: Pts with de novo in vitro carbo resistance have more rapid relapse, and can be prospectively rapidly identified before initial CT (time required for MiCK assay 48 hours). Alternative drugs or combinations with in vitro activity (still using drugs within national evidence based treatment guidelines) can be identified with the MiCK assay. This suggests that for pts with relapsing disease with clinically apparent carbo resistance, the MiCK assay can identify individualized CT for such pts. This study gives the framework for a prospective randomized phase III trial of assay-directed CT versus standard CT in platinum-resistant ovarian CA. Clinical trial information: NCT 00443196.