CDK inhibitor shows promise in metastatic breast cancer

The oral drug LY2835219 demonstrated encouraging activity as single-agent therapy for patients with metastatic breast cancer, according to study results presented at the American Association for Cancer Research Annual Meeting.

The benefits were particularly apparent among patients with hormone receptor-positive disease.

“Hormone receptor positivity currently is the best available biomarker to select patients with breast cancer most likely to benefit from this treatment,” Amita Patnaik, MD, associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio, said during a press conference. “The data are rather encouraging for a very heavily pretreated patient population.”

Amita Patnaik

Patnaik and colleagues evaluated LY2835219 (Eli Lilly) — which inhibits cyclin-dependent kinases 4 and 6 — in 132 patients with one of five tumor types: breast cancer, glioblastoma, melanoma, lung cancer and colon/rectum cancer.

All patients received LY2835219 orally every 12 hours for 28 days. Treatment continued until tumor progression or unacceptable toxicity.

The cohort included 47 patients (median age, 55 years) with metastatic breast cancer, the majority of whom (76.5%) had HR-positive disease. These patients had undergone a median seven prior therapies, no longer derived benefit from standard treatment, had measurable disease based on RECIST criteria and had an ECOG performance status of ≤2. Patients were required to cease other treatments with the exception of hormone therapy.

Nine (19%) of the 47 patients with metastatic breast cancer demonstrated confirmed partial response, 24 (51%) achieved stable disease and 11 (23%) progressed while on treatment. Among patients with HR-positive metastatic breast cancer, researchers reported a 25% partial response rate and a 55% stable disease rate. The disease control rate — a combination of complete responses, partial responses and stable disease — was 70% overall and 81% for HR-positive patients.

The current estimate of median PFS is 9.1 months, although that figure remains “a moving target” because 18 patients still remain on treatment, Patnaik said.

The most common toxicities among patients with breast cancer were diarrhea, nausea, fatigue, neutropenia, vomiting, thrombocytopenia and leukopenia. However, most adverse events were grade 1 or grade 2, and no patients discontinued treatment due to drug-related toxicities, Patnaik said.

“Although our study was not designed to compare patient outcomes based on HR status, the clinical benefit rate was 61 percent in our patients with HR-positive breast cancer, which means patients had disease control for longer than 24 weeks or had their tumors reduce in size by more than 30 percent,” Patnaik said. “These results indicate … the drug warrants further evaluation in larger, confirmatory studies.”

For more information:

Patnaik A. Abstract #CT232. Presented at: AACR Annual Meeting; San Diego; April 5-9, 2014.

Disclosure: The study was funded by Eli Lilly. Patnaik reports research funding and honoraria from Eli Lilly.