At the 42nd American Society of Clinical Oncology (ASCO) annual meeting in Atlanta, Eli Lilly and Co announced results of a phase II trial evaluating its thoracic cancer drug pemetrexed(Drug information on pemetrexed) (Alimta) in first-line treatment of metastatic breast cancer. The study also detailed exploratory pharmacogenomic analyses to potentially identify the presence of specific biomarkers for pemetrexed. Lilly's study is among the first bodies of research evaluating the potential use of biomarkers with chemotherapy agents.

On Track for Further Evaluation

The phase II study was a randomized, double-blind trial of 92 patients with locally advanced or metastatic breast cancer. The two sets of patient groups were given two different doses of pemetrexed. The study concluded that since efficacy and safety for both doses were similar, the lower dose (600 mg/m²) is suitable for further study. In addition, exploratory biomarker analysis suggests an efficacy correlation for folypolyglutamate synthase (FFGS) and thymidine phosphorylase (TP).

"We are encouraged by these results," said Allen Melemed, MD, Lilly associate medical director and a study author. "And while it's too soon to be conclusive, it does seem like we're heading in the right direction. Our hope is to be able to offer patients and their doctors more choices, and to one day help them know with more certainty which ones work for them."

Lilly is considering plans for a phase III trial, as well as further evaluation of the biomarkers that were explored.

Study Details

The trial enrolled women with a histologic/cytologic diagnosis of breast cancer and evidence of locally recurrent disease or distant metastasis not amenable to local therapy. Patients received pemetrexed (arm A: 600 mg/m²; arm B: 900 mg/m²) on a 21-day cycle, with a median of six cycles delivered. All patients received folic acid(Drug information on folic acid) and vitamin B12 supplementation. Forty-seven patients, aged 33 to 81 years (with a median age of 57), enrolled in arm A and 45 in arm B.

Arms A and B had response rates of 17% and 15%, median progression-free survival times of 4.2 and 4.1 months, and median times to tumor progression of 4.2 and 4.6 months, respectively. Toxicity was mild in both arms (grade 3/4), with neutropenia occurring in less than 20% of patients and leukopenia in less than 9%. Nonhematologic side effects were mild and similar to those commonly experienced when pemetrexed is used as monotherapy, eg, disorders of the blood and lymphatic system, gastrointestinal disorders, fatigue, rash, and desquamation.

Primary tumor samples from 49 patients were assessed for gene expression. Two markers, FPGS and TP, showed the most conclusive results. Best response rates and median times to tumor progression for high vs low FPGS expression subgroups were 37.5% vs 10% and 8.57 vs 2.99 months. The results for TP were 27.6% vs 6.2% and 5.39 vs 1.94 months.

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