LY2835219 Shows Strong Single-Agent Activity in Preliminary Study in Metastatic Breast Cancer

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Amita Patnaik, MD

LY2835219 in Metastatic Breast Cancer

Inhibitors of cyclin-dependent kinase (CDK) 4/6 are getting attention as a novel approach for the treatment of breast cancer. At the 2014 American Association for Cancer Research (AACR) Annual Meeting, two presentations focused on these new agents. One was a phase II study of Pfizer’s compound palbociclib as first-line therapy (see page 1) and the second was a preliminary study of Lilly’s compound LY2835219 in heavily pretreated patients.

The Pfizer study showed that the combination of palbociclib plus letrozole doubled progression-free survival as first-line treatment of metastatic breast cancer. In contrast, LY2835219 appears to have strong single-agent activity in this disease. Both studies identified hormone receptor positivity as the major biomarker for selecting patients for treatment with these agents.

Phase I Trial

“These results confirm single-agent activity of LY2835219. This compound appears to be very effective in heavily pretreated patients with metastatic breast cancer. Although our study was not designed to compare outcomes based on hormone receptor status, results in the hormone receptor–positive patients were very encouraging,” said lead author Amita Patnaik, MD, Associate Director of Clinical Research at South Texas Accelerated Research Therapeutics in San Antonio.

The phase I trial reported by Dr. Patnaik explored the effect of LY2835219 in five different tumor types (n = 132). At the AACR meeting, Dr. Patnaik reported results in a cohort of 47 patients with metastatic breast cancer who received a median of seven prior therapies. Median age was 55 years. The majority had two or more metastatic sites; 74% had visceral metastases. Thirty-six patients (76%) were hormone receptor–positive.

Among all patients, 11 (19%) had a partial response and 24 (29.8%) had stable disease. Progressive disease occurred in 11 patients (23.8%) who received LY2835219. Progression-free survival was estimated at 9.1 months.

Among hormone receptor–positive patients, 9 (25%) had confirmed partial responses and 20 (56%) had stable disease, including 2 with unconfirmed partial responses; the clinical benefit rate was 61%, and disease control rate was 81%. Responses were durable, Dr. Patnaik said.

All of the responders and 20 of 24 patients with stable disease were hormone receptor–positive. Eighteen patients with hormone receptor–positive disease are still being treated with LY2835219. The drug will move forward for further evaluation in breast cancer.

Drug-Related Toxicity

The most common side effects of LY2835219 were diarrhea, fatigue, nausea, vomiting, leukopenia, and neutropenia. “Side effects were tolerable, and no patient discontinued study due to drug-related toxicity,” Dr. Patnaik said.

Fatigue was the dose-limiting toxicity and 200 mg every 12 hours was identified as the maximum tolerated dose.

The investigators determined that neutropenia did not correlate with clinical benefit. ■

Disclosure: Dr. Patnaik has received research funding from and has been a consultant for Eli Lilly.


1. Finn RS, Crown JP, Lang I, et al: Final results of a randomized phase II study of PD 0332991, a cyclin-dependent kinase (CDK)-4/6 inhibitor, in combination with letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1/TRIO-18). AACR Annual Meeting. Abstract CT101. Presented April 6, 2014.

2. Patnaik A, Rosen LS, Tolaney SM, et al: Clinical activity of LY2835219, a novel cell cycle inhibitor selective for CDK4 and CDK6, in patients with metastatic breast cancer. AACR Annual Meeting. Abstract CT232. Presented April 7, 2014.

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