Lilly Breast Cancer Studies Explore Potential Role of Pharmacogenomics in Customizing Chemotherapy

At the 42nd American Society of Clinical Oncology (ASCO) annual meeting in Atlanta, Ga., Eli Lilly and Company has unveiled two breast cancer studies involving pharmacogenomics and its chemotherapies GEMZAR^® (gemcitabine HCl) and ALIMTA^® (pemetrexed).

They are among the early trials involving pharmacogenomics in breast cancer treatment.

Richard Gaynor, M.D., vice president, cancer research and global oncology platform leader for Lilly said, "While these are preliminary trial results, the hope is that in the future, treatment-predictive pharmacogenomics may lead to highly tailored treatments that offer optimum patient outcomes."

While breast cancer has been the focus of much research and attention over the years, it is only in recent times that this cancer has been recognized as not one but many diseases, according to Vered Stearns, M.D., assistant professor of oncology, Johns Hopkins School of Medicine and an ASCO presenter on the subject of breast cancer and pharmacogenomics.

Stearns said, "This new outlook on breast cancer will move treatment from the 'one-size-fits-all' to the personalized medicine approach."

"Right now, we treat cancer based on stage, age, other diseases, etc., as opposed to what the actual cancer of that woman looks like," said Stearns, adding., "And we tend to over-treat because we're worried about the cancer coming back."

"Pharmacogenomics can help analyze tumors' specific genetic make- up to potentially guide cancer treatment decisions, thereby avoiding unnecessary toxicity, and leading to better patient outcomes."

According to Gaynor, chemotherapies, which remain the foundational therapies of choice, may experience a resurgence if pharmacogenomics can be employed in hopes of maximizing treatment success.

This "right patient, right drug, right time" philosophy is what guides Lilly Oncology. "Cancer is personal - it affects different people differently, from a biological, physiological, and psychological perspective," said Gaynor.

"And Lilly is responding by working to personalize and optimize its prevention and treatment, with innovative research and solutions including chemotherapies, targeted agents and pharmacogenomics."

In a correlative study on a combined analysis of approximately 90 women receiving neoadjuvant (pre-surgical) chemotherapy, researchers sought to identify gene expression profiles/biomarkers that predict patients' response to chemotherapy. They also tried to determine whether these biomarkers were drug-specific.

Scientists from the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center and Lilly Research Laboratories in Indianapolis, Ind. evaluated two groups of locally advanced breast cancer patients receiving chemotherapy.

DNA microarray analysis was performed on pre-treatment core biopsies from the patients.

They then treated the first group of patients (L9819) with four cycles of doxorubicin + cyclophospharmide (AC), followed by four cycles of paclitaxel (Taxol^®) or paclitaxel + trastuzumab (Herceptin^®).

The second group of patients (S329) received four cycles of Gemzar + doxorubicin followed by four cycles of Gemzar + cisplatin. Clinical response was based on RECIST criteria.

Successful microarrays were obtained on 45 of the L9819 group and 46 of the S329 group, and separate analyses on each dataset identified gene expression patterns that predicted with 75-80 percent accuracy clinical response on those patients that completed all eight cycles of chemotherapy.

Comparisons of both L9819 and S329 predictors indicated that the study may provide the means to predict response related to both general and drug- specific chemotherapy, in this case Gemzar.

Another Lilly study compared two doses of Alimta in advanced breast cancer, and attempted to identify potential biomarkers.

The main objective of the study was to access response rate on the two arms, and conduct exploratory biomarker analysis.