Enzastaurin Shows Favorable Results in Late-Stage Lung Cance

[RandyW]

Targeted, Oral Agent Enzastaurin Shows Favorable Results in Late-Stage Lung Cancer

Study Supports Lilly's Commitment to Advances in Lung Cancer Treatment

CHICAGO, June 2 /PRNewswire-FirstCall/ -- Enzastaurin, an

investigational targeted, oral agent under development by Eli Lilly and

Company, showed encouraging results in treating patients with late-stage

non-small cell lung cancer (NSCLC), according to data presented today at

the 43rd Annual Meeting of the American Society of Clinical Oncology

(ASCO).

The data presented were gathered from a multicenter Phase II study of

enzastaurin as a second- or third-line treatment of NSCLC (ASCO Abstract

#7543(i)). The rationale for the study was based on enzastaurin's unique

mechanism of action as a serine/threonine kinase inhibitor, which is

believed to suppress signaling through the PKC-beta and PI3K/AKT pathways.

Historically, over-expression and activity of PKC-beta and PI3K/AKT have

been associated with poor prognosis and treatment resistance in NSCLC. The

primary objective of the study was progression-free survival at six months.

Secondary endpoints were safety and overall survival at 12 months.

"These data in NSCLC shed new light on the potential versatility of

this agent," said Richard Gaynor, M.D., vice president, cancer research and

global oncology platform leader for Lilly. "Our objective with enzastaurin

is to continue investigating the efficacy and safety of this unique

molecule in order to determine the diseases where enzastaurin could have

the most positive impact on patients."

In the study, patients received 500 mg of oral enzastaurin, once daily,

until disease progression or unacceptable toxicity occurred. In the 54

patients enrolled, the median progression-free survival was 1.9 months (95%

Confidence Interval: 1.7-1.9) and the progression-free survival rate at six

months was 14% (95% CI: 4.4%-23.6%). The median overall survival was 9.9

months (95% CI: 6.5-14.6). The overall survival rate at 12 months was 46.3%

(95% CI: 32.1%-60.5%). The most common toxicity was fatigue. Additional

toxicities observed included ataxia (n=1), thromboembolism (n=1), anemia

(n=1) and dizziness.

"Based on the encouraging survival and tolerability data gathered thus

far, further evaluation of enzastaurin in NSCLC, as a single agent or in

combination, is warranted," said chief investigator for the study, Gerold

Bepler, M.D., Ph.D., chief of thoracic oncology at the H. Lee Moffitt

Cancer Center and Research Institute in Tampa, Florida.

Additional data presented at ASCO this year examined studies of

enzastaurin in breast cancer, first-line glioblastoma, ovarian and

pancreatic cancers, as well as other solid tumors. Specifically, the data

included: testing enzastaurin on cell signaling, proliferation and

apoptosis in breast cancer, testing in Phase I/II with radiation

combination therapy for first- line treatment of glioblastoma multiforme, a

pre-clinical study on ovarian chemo-resistant cancer cell lines, testing

for growth suppression in pancreatic cancer, as well as dosage testing on

other solid tumors.

"Through a constant stream of innovation, we remain committed to

fighting cancer," said Gaynor. "By aggressively studying enzastaurin across

multiple tumor types, we believe that we will find appropriate and

innovative uses for this targeted therapy to help benefit patients."

Enzastaurin

Enzastaurin is an oral, serine threonine kinase inhibitor which

selectively targets the PKC-beta and PI3K/AKT signaling pathways. By

blocking these key pathways frequently over-expressed in a wide variety of

cancers, enzastaurin suppresses tumor cell proliferation, induces tumor

cell death and inhibits tumor-induced angiogenesis. Enzastaurin is being

evaluated in a Phase III trial (currently enrolling patients) as a

maintenance therapy for the treatment of diffuse large B-cell lymphoma

(DLBCL), as well as being evaluated in several Phase II studies across a

variety of more common tumor types including: breast, colon, lung, ovarian

and prostate cancers. More details on the enzastaurin Phase III trial, as

well as information on global recruitment sites, may be found at

http://www.clinicaltrials.gov, http://www.lillytrials.com or by calling 1-877-CTLilly

(1-877-285-4559).

About Lilly Oncology, a Division of Eli Lilly and Company

For more than four decades, Lilly Oncology has been collaborating with

cancer researchers to deliver innovative treatment choices and valuable

programs to patients and their physicians. Inspired by courageous patients

living with cancer, Lilly Oncology is providing treatments that are

considered global standards of care and developing a broad portfolio of

novel targeted therapies to accelerate the pace and progress of cancer

care. To learn more about Lilly's commitment to cancer, please visit

http://www.LillyOncology.com.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing

portfolio of first-in-class and best-in-class pharmaceutical products by

applying the latest research from its own worldwide laboratories and from

collaborations with eminent scientific organizations. Headquartered in

Indianapolis, Ind., Lilly provides answers -- through medicines and

information -- for some of the world's most urgent medical needs.

P-LLY

[neilb]

My read of the abstract is not nearly so positive as the press release. None of the 54 patients had a partial response and only 35% had stable disease. This doesn't compare very favorably with other second-line therapies.

Here's the abstract:

http://www.asco.org/portal/site/ASCO/me ... ctID=30343

[RandyW]

thanks Neil Appreciate that

[neilb]

On the other hand, if I'm reading things correctly, there does appear to be positive news about Alimta, Taxol, Tarceva, and Avastin, among other drugs (see also Gemzar, Oxaliplatin, and Axitinib). Much of the positive news is in second-line and later settings.