This randomized, double-blind comparison demonstrates that biosimilar filgrastim (EP2006) and the US-licensed reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially increasing access to filgrastim treatment.

Purpose Currently, antiangiogenic strategies in metastatic breast cancer have demonstrated modest improvements in progression-free survival (PFS) but not improved quality or duration of survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab is a human immunoglobulin G1 antibody that binds vascular endothelial growth factor receptor-2 and blocks ligand-stimulated activation. The ROSE/TRIO-012 trial evaluated ramucirumab with docetaxel in unresectable, locally recurrent, or metastatic breast cancer. Patients and Methods In this double-blind, placebo-controlled, randomized, multinational phase III trial, 1,144 patients with human epidermal growth factor receptor 2 (HER2) –negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomly assigned at a two-to-one ratio to receive docetaxel 75 mg/m2 plus ramucirumab 10 mg/kg or docetaxel 75 mg/m2 plus placebo once every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographic region. An independent data monitoring committee oversaw the trial. The primary end point was investigator-assessed PFS. Results Median PFS in patients treated with ramucirumab plus docetaxel was 9.5 months, compared with 8.2 months in patients who received placebo plus docetaxel (hazard ratio [HR], 0.88; P = .077). Median overall survival was 27.3 months in patients who received ramucirumab plus docetaxel, compared with 27.2 months in patients who received placebo plus docetaxel (HR, 1.01; P = .915). Toxicities seen at significantly higher rates in patients receiving ramucirumab included fatigue, hypertension, febrile neutropenia, palmar-plantar erythrodysesthesia syndrome, and stomatitis. Conclusion Addition of ramucirumab to docetaxel in HER2-negative advanced breast cancer did not meaningfully improve important clinical outcomes.

629 Background: CT-P6(C) is an anti-HER2 MoAb, a biosimilar to trastuzumab (T). This trial is a global phase III study to compare C with T, both in combination with paclitaxel (P) as first-line treatment in women with HER2+ MBC. Methods: 475 patients with centrally confirmed HER2+ MBC were randomized to receive either C+P (n=244) or T+P (n=231). Patients had to have a baseline LVEF ≥50% and no history of serious cardiac disease. Study medication was as follows: C or T 8 mg/kg i.v. (day 1), followed by 3-weekly C or T 6 mg/kg. P (175 mg/m23-weekly) was co-administered. The primary endpoint was overall response rate (ORR) as determined by independent review. Pooled analysis with data from phase I/IIb (NCT01084863) and III studies (NCT01084876) was predefined and endorsed by the EMA. Patient safety was monitored throughout the study by an independent data monitoring committee. Treatment was continued until disease progression, death or patient’s withdrawal. Results: In the pooled ITT population, ORR was 57% for C+P and 62% for T+P (difference: 5%; 95% CI: -0.14, 0.04) during the first 8 cycles of treatment. The limits of the 95% CIs for the difference in the proportions of responders were contained within the pre-defined range [-0.15, 0.15] required for equivalence. Median time to progression and median time to response were 11.07 vs. 12.52 months (P =0.10), and 1.38 vs. 1.38 months (P =0.37) for C+P and T+P, respectively. Frequency of treatment-related AEs is shown in the Table. Conclusions: Equivalence of C and T was observed for ORR in patients with HER2+ MBC in combination with P as first-line therapy. Secondary efficacy endpoints also supported the comparability between C and T. C was well tolerated with a safety profile comparable to that of T. Clinical trial information: NCT01084876. [Table: see text]

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Based on a modified dosing protocol designed to optimize efficacy, an open-label EFL vs. capecitabine (4:3 randomization) Phase 2 trial for metastatic breast cancer is in progress. Eniluracil inactivates dihydropyrimidine dehydrogenase, thereby preventing the formation of α-fluoro-β-alanine, and conferring 100% oral bioavailability and a 5 hr half-life on 5-fluorouracil (5-FU). Study drugs are administered orally for 1st- or 2nd-line treatment for metastatic disease in patients previously treated with an anthracycline and a taxane. Arm 1: eniluracil (40 mg) taken 11–16 hr before 5-FU (30 mg/m2); leucovorin (30 mg) taken with 5-FU and the next day. The regimen is administered once/week for 3 weeks/4 weeks. Arm 2: capecitabine (1000 mg/m2) taken bid for 14 days/21days. Arm 2 patients with disease progression could crossover to take EFL in Arm X. Two sites in the USA and 19 in Russia are enrolling. Currently, 115 patients (21% are 1st-line, 70% had previous 5-FU treatment) are enrolled and 83 have had tumor assessments. EFL was well tolerated with no unexpected toxicities. As of May 2012, there were 11, 7, & 1 partial responses in Arms 1, 2, & X, respectively. The primary endpoint, progression-free survival, will be determined approximately 7.5 months after the trial is enrolled with 140 evaluable patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-01.