894P - PRECEDENT subset analysis: safety and disease control with vintafolide monotherapy following discontinuation of pegylated liposomal doxorubicin (PLD)

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Ovarian Cancer
Presenter Dariusz Wydra
Citation Annals of Oncology (2014) 25 (suppl_4): iv305-iv326. 10.1093/annonc/mdu338
Authors D. Wydra1, S.A. Ghamande2, N.Y. Gabrail3, E. Nowara4, M. Bidzinski5, S. Depasquale6, R. Clark7, R.T. Penson8
  • 1Dept Of Gynecology, Gynecological Oncology, And Gynecological Endocrinology, Medical University of Gdansk, 80-402 - Gdansk/PL
  • 2Gynecologic Oncology, Georgia Regents University, Augusta/US
  • 3The Cancer Treatment And Research Facility, Gabrail Cancer Center, Canton/US
  • 4Clinical And Experimental Oncology Department, Cancer Center and Institute Gliwice Branch, Gliwice/PL
  • 5Department Of Gynecological Oncology, Specialist Hospital Inflancka, Warsaw/PL
  • 6Department Of Obstetrics And Gynecology, Chattanooga’s Program in Women’s Oncology, Chattanooga/US
  • 7Clinical Development, Endocyte, Inc., West Lafayette/US
  • 8Hematology/oncology, Massachusetts General Hospital, Boston/US

Abstract

Aim

Differential expression of the folate receptor (FR) in normal (low) and malignant (high) tissues makes FRs promising therapeutic targets. The randomized phase II PRECEDENT trial (NCT00722592) comparing vintafolide (Vinta), a folic-acid/desacetylvinblastine conjugate, and PLD vs PLD alone in platinum-resistant ovarian cancer (PROC) patients (pts) demonstrated progression-free survival (PFS) benefit in the combination arm (5.0 vs 2.7 months, respectively) and etarfolatide could predict Vinta responders (Naumann et al, JCO. 2013;31:4400). This subset analysis evaluated safety and disease control in pts who discontinued PLD and continued on single-agent Vinta.

Methods

PROC pts (≥18 years) with ECOG PS of 0-2 and <2 prior systemic cytotoxic regimens were randomized (2:1) to Vinta + PLD or PLD alone. Per protocol, pts in the Vinta + PLD arm who had reached maximum allowable cumulative dose of PLD, or who discontinued PLD due to unacceptable toxicity, could continue with single-agent Vinta. Study endpoints included PFS, response rate, and safety.

Results

The intention-to-treat population was 149 pts (Vinta + PLD, n = 100; PLD, n = 49). Twenty-two pts from the combination arm discontinued PLD and continued on Vinta alone. The most common reasons for PLD discontinuation were maximum permitted dose (n = 6) and hand-foot syndrome (n = 9). Median number of cycles of Vinta alone was 4 (range: 1-16). In pts receiving only Vinta, median time from monotherapy to progression, death, or treatment discontinuation was 4.3 months, and median survival time was 18 months. Treatment toxicity in these 22 pts was less during treatment with Vinta alone, compared with the Vinta + PLD combination, for the following (respectively): gastrointestinal disorders (9.1% vs 95.5%); skin or soft tissue disorders (9.1% vs 90.9%); hematologic disorders (9.1% vs 77.3%).

Conclusions

Following discontinuation of PLD, Vinta monotherapy resulted in continued disease control with a favorable side-effect profile. These data indicate a potential benefit of continued Vinta monotherapy for patients unable to continue on the Vinta + PLD combination.

Disclosure

R. Clark: Other substantive relationships: Employee of Endocyte; R.T. Penson: Scientific Advisory Board Member: Endocyte Corporate-sponsored research: Clinical Trial Funding - PI for Endocyte. All other authors have declared no conflicts of interest.