Results of a phase II study of pemetrexed as first-line chemotherapy for advanced or metastatic breast cancer

Abstract

1073 Background: Pemetrexed, a multitargeted antifolate, inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyl transferase (GARFT), a folate-dependent enzyme involved in purine synthesis. Inhibition of these targets contributes to its cytotoxicity. As palliation is the primary goal for patients (pts) with advanced breast cancer, safe and efficacious new single-agent options are needed. Methods: The primary objective was response rate (RECIST); secondary objectives were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Women with advanced or metastatic disease continued Tx until intolerable toxicity or PD. Treatment (Tx): pemetrexed (P) 600 mg/m2 IV on Day 1 each 14-day cycle. Std dexamethasone premed (day prior, day of, and day after) was given, unless contraindicated. Folic acid and vitamin B12 were given throughout the study. Results: 37 pts enrolled; 36 received >1 dose of P and 34 were evaluable. The median age was 61.4 yrs; ECOG 0/1 was 51%/49%; 68% were ER+ and 54% were PR+. Prior Tx included adjuvant chemotherapy (60%), or hormones/biologics (60%). Pts received a median of 6 cycles of P (range, 1 - 21). 15 pts had doses delayed (n=9) or reduced (n=6). Based on 34 evaluable pts, the overall response rate (ORR) was 26.5% (1 CR, 3% and 8 PR, 23.5% for an ORR of 26.5 % (CI 12.9, 44.4); 16 pts had SD, 47% with 3 pts, 9% having SD for >6 months for a Clinical Benefit Rate (ORR + SD >6 mos) of 35%; 9 had PD (26.5%). The median DOR was 6.5 mos (range, 1.6 - 15.1). Median PFS was 4.1 mos (range, <1 - 11.3) and 6-month PFS was 31.2%. Median OS was 18.9 mos (range, <1 - 22.6). Reasons off Tx were progression (59.5%), toxicity (13.5%), MD or pt request/WD consent (11%, each), and other (5%, 1 pt each Tx error and ineligibility after Dose 1). Grade 3–4 Tx-related toxicities were neutropenia (36%); leukopenia, fatigue (14%, each); anemia (11%); hyperglycemia, asthenia and nausea (6%, each). Mild alopecia was seen in 11% of patients. Conclusions: In this small phase II study single-agent pemetrexed showed moderate activity in the first line setting with acceptable toxicity and no significant alopecia. This research was sponsored by Eli Lilly and Company, Indianapolis, IN. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly AstraZeneca Oncology, GlaxoSmithKline, Novartis Abraxis Oncology, Eli Lilly, Pfizer Oncology