Phase III trial of induction gemcitabine (G) or paclitaxel (T) plus carboplatin (C) followed by elective T consolidation in advanced ovarian cancer (OC): Interim analysis of induction chemotherapy

Abstract

5536 Background: Induction TC is a standard of care for advanced OC. GC is approved for use in recurrent platinum-sensitive OC. Phase II trials show G + platinum to be active as first-line therapy for OC. Also, evidence suggests that 12-month T consolidation improves progression- free survival (PFS). This trial compared safety and efficacy of GC and TC induction regimens followed by elective T consolidation. This interim disclosure, permitted by protocol, reports toxicity and response results for the first 449 pts randomized to induction regimens. Methods: Pts enrolled with histologic diagnosis and prior resection of Stage Ic-IV epithelial ovarian, primary peritoneal, or fallopian tube carcinomas were randomized to two induction arms. GC arm was given G 1,000 mg/m2 on Days 1, 8 plus C AUC 5 on Day 1. TC arm was given T 175 mg/m2 plus C AUC 6 on Day 1. Up to six 21-day cycles were permitted. Pts with CR were allowed consolidation therapy with T 135 mg/m2 every 28 days up to 12 months. Non-CR patients were given single-agent crossover therapy (GC: T 175 mg/m2 on Day 1; TC: G 1,000 mg/m2 on Days 1, 8) every 21 days until CR, PD, or undue toxicity. Best response was assessed in pts with measurable disease by RECIST; CR required normalized CA-125. The 2-sided Fisher's exact test determined p-values. Results: Enrollment was stopped in 2006 at 919 pts and the protocol modified to allow PFS as primary endpoint. Interim results are summarized below. Demographics were well balanced between arms. Anemia, thrombocytopenia, and platelet transfusions were greater for GC, while neuropathy and severe alopecia were greater for TC. ORR and DCR were not statistically different in the two induction arms. Conclusions: Based upon this interim analysis, toxicity profiles for each induction arm were consistent with prior clinical experience. Response rates were comparable for GC and TC therapies. Parameter Induction GC Induction PC p- Value Demographics (enrolled pts) N=225 N=224 Median age (range) 60 (22–84) 61 (27–86) FIGO stage at initial surgery, n (%) IC 11 (4.9%) 12 (5.4%) II 27 (12.0%) 22 (9.8%) III 153 (68.0%) 158 (70.5%) IV 34 (15.1%) 31 (13.8%) Zubrod performance status, n (%) 0 137 (60.9%) 134 (59.8%) 1 69 (30.7%) 79 (35.3%) 2 13 (5.8%) 7 (3.1%) Toxicity (pt-based), n (%) N=219 N=220 G3–4 Neutropenia 173 (79.0%) 181 (82.3%) 0.4001 G3–4 Thrombocytopenia 143 (65.3%) 40 (18.2%) <0.0001 G3–4 Anemia 52 (23.7%) 20 (9.1%) <0.0001 G3–4 Fatigue 18 (8.2%) 11 (5.0%) 0.1848 G3–4 Nausea 9 (4.1%) 6 (2.7%) 0.4460 G3–4 Vomiting 7 (3.2%) 5 (2.3%) 0.5752 >G2 Neuropathy 24 (11.0%) 43 (19.5%) 0.0165 G3–4 Febrile neutropenia 2 (0.9%) 7 (3.2%) 0.1752 G3–4 Myalgia 4 (1.8%) 3 (1.4%) 0.7240 G2 Alopecia 79 (36.1%) 110 (50.0%) 0.0038 RBC transfusion 15 (6.8%) 11 (5.0%) 0.4274 Platelet transfusion 7 (3.2%) 0 (0.0%) 0.0073 Best response, n (%) N=66 N=58 Complete response (CR) 30 (45.5%) 26 (44.8%) Partial response (PR) 13 (19.7%) 12 (20.7%) Stable disease (SD) 5 (7.6%) 8 (13.8%) Progressive disease (PD) 6 (9.1%) 4 (6.9%) Unknown 12 (18.2%) 8 (13.8%) ORR (CR+PR) 43 (65.2%) 38 (65.5%) >0.999 DCR (CR+PR+SD) 48 (72.7%) 46 (79.3%) 0.410 Pts in T consolidation, n (% of enrolled) 111 (49.3%) 110 (49.1%) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company