Study supports activity of GEMZAR in the treatment of early-stage breast cancer

June 02, 2007

CHICAGO, June 2, 2007 -- GEMZAR® (gemcitabine HCl for injection), approved in combination with paclitaxel (Taxol®) in the first-line, post-surgical treatment of metastatic breast cancer, was the subject of a study presented today with encouraging results in the pre-surgical treatment of breast cancer. The study was presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO).

Results showed that adding GEMZAR to the current standard-of-care treatment was a promising regimen for patients with stage II-III breast cancer. Eli Lilly and Company, the manufacturer and marketer of GEMZAR, also cited five completed or ongoing Phase III trials which will further study GEMZAR as a chemotherapeutic foundation for the treatment of early-stage breast cancer.

Today's Phase II study (Abstract # 595 ) evaluated the addition of GEMZAR to the current standard-of-care of epirubicin and cyclophosphamide followed by paclitaxel in patients with stage II-III breast cancer. The treatment schedule was a dose-dense sequential neoadjuvant (pre-surgical) chemotherapy combination, meaning that the combination was administered at shorter intervals between treatments. Results showed a promising regimen in terms of pathologic complete response (pCR-the absence of invasive tumor in the breast). In addition, patients who tested positive for the HER-2 gene also were given trastuzumab (Herceptin®) and demonstrated additional response.

"The data released today reflects our ongoing, aggressive research plan involving GEMZAR as a key therapeutic foundation for the treatment of breast cancer," said Allen Melemed, M.D., medical director, global oncology at Lilly. "We are encouraged with the activity GEMZAR has shown in this breast cancer study."

Enrollment has been completed in one trial, and is ongoing in an additional four, Phase III early-stage breast cancer studies evaluating the addition of GEMZAR to commonly-used treatment regimens. Two adjuvant (post-surgical) therapy trials, NSABP B-38 (4,400 patients) and TANGO (3,000 patients), will compare the addition of GEMZAR to the paclitaxel arm of each study. A third adjuvant trial, SUCCESS (3,600 patients), will compare the addition of GEMZAR to a docetaxel-based regimen. Two additional trials, which are neoadjuvant specific, NSABP B-40 (1,200 patients) and Neo-TANGO (800 patients), will evaluate the addition of GEMZAR to the paclitaxel or docetaxel arm of the treatment regimen. For more information on these studies, log on to www.lillytrials.com or www.clinicaltrials.gov.

More About ASCO Abstract # 595

The trial enrolled stage II-III breast cancer patients (with a median age of 45), including inflammatory tumors, a type of breast cancer that causes the breast to swell, redden and feel warm. Of the 73 patients enrolled in the study, 42 (57.5%) were classified as T2; 12 (16.5%) as T3, and; 19 (26%) as T4, which included 13 patients with inflammatory tumors. A T-classification represents the stage of the tumor with T4 being the most advanced. A biopsy was performed before treatment for the biomarker component of the study.

Patients received a first sequence of epirubicin and cyclophosphamide (90/600 mg/m2) for three cycles followed by a second sequence of paclitaxel and GEMZAR (150/2500 mg/m2) for six cycles. Treatment was administered on day one, every two weeks, with growth factor support. HER-2 positive patients (20 patients, 27.3%), were given trastuzumab (2 mg/kg with a loading dose 4 mg/kg) concomitantly. Afterward, the patients underwent surgery, radiotherapy and adjuvant hormonal therapy according to institutional practice.

All patients from the study showed response to the regimen. Of the entire study group, 27 (36.9%) patients achieved a pCR (absence of invasive tumor in the breast), with 50% representation from the HER-2 positive patients who also were given trastuzumab. Forty-seven patients (64.4%) underwent conservative surgery.

The grade 3/4 hematological toxicities were: leukopenia in six patients (9%); neutropenia (a decrease in white blood cells) in eight patients (12%), and; anemia (a decrease in red blood cells) in one (2%). Nausea (13%) and vomiting (15%) were the most frequent grade 3/4 non-hematological toxicities. Asymptomatic decrease in cardiac ejection fraction was observed in one patient treated with trastuzumab with subsequent normalization.
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About Breast Cancer

Breast cancer is the most common form of cancer among women, affecting nearly one out of every eight women. The disease is diagnosed in more than 1.1 million women worldwide each year. Breast cancer progresses in stages based on tumor size, how the cancer affects the lymph nodes and whether it has metastasized to other parts of the body. In general, individuals with earlier stages of disease have better chances for long-term survival and recovery.

GEMZAR
Indications
GEMZAR in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.

GEMZAR is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (stage IIIA or IIIB), or metastatic (stage IV) non-small cell lung cancer.

GEMZAR is indicated as first-line treatment for patients with locally advanced (nonresectable stage II or stage III) or metastatic (stage IV) adenocarcinoma of the pancreas. GEMZAR is indicated for patients previously treated with 5-FU.

GEMZAR in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.

Important Safety Information for GEMZAR Myelosuppression is usually the dose-limiting toxicity with GEMZAR therapy.

Contraindication
Known hypersensitivity to GEMZAR. Anaphylactoid reaction has been reported rarely.

Warnings
Infusion times of GEMZAR longer than 60 minutes and more frequent than weekly dosing have been shown to increase toxicity.

Pulmonary toxicity has been reported with the use of GEMZAR. In cases of severe lung toxicity, GEMZAR therapy should be discontinued immediately and appropriate supportive care measures instituted.

Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of GEMZAR. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been rarely reported. The majority of the cases of renal failure leading to death were due to HUS.

Serious hepatotoxicity, including liver failure and death, has been reported very rarely in patients receiving GEMZAR alone or in combination with other potentially hepatotoxic drugs.

GEMZAR is Pregnancy Category D. GEMZAR can cause fetal harm when administered to a pregnant woman.

Precautions
Use caution in patients with pre-existing renal impairment or hepatic insufficiency. Administration of GEMZAR may exacerbate underlying hepatic insufficiency.

The optimum regimen for safe administration of GEMZAR with therapeutic doses of radiation has not yet been determined in all tumor types. GEMZAR has radiosensitizing activity and radiation recall reactions have been reported.

It is not known whether GEMZAR or its metabolites are excreted in human milk.

The effectiveness of GEMZAR in pediatric patients has not been demonstrated.

The toxicities of GEMZAR observed in pediatric patients were similar to those reported in adults.

GEMZAR clearance is affected by age as well as gender.

Patients receiving therapy with GEMZAR should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents.

Monitoring and Dosage Modifications
Dosage adjustments for hematologic toxicity may be required.

Serum creatinine, potassium, calcium, and magnesium should be monitored during combination therapy with cisplatin.

Patients should be assessed with a CBC, including differential and platelet count, prior to each dose of GEMZAR. Modify or suspend therapy according to the Dosage Reduction Guidelines in the full Prescribing Information.

Hepatic and renal function (including transaminases and serum creatinine) should be evaluated prior to therapy with GEMZAR and periodically thereafter.

Adverse Events
The most severe adverse events (grades 3/4) with GEMZAR plus paclitaxel for the treatment of patients with MBC were neutropenia (48%); alopecia (18%); leukopenia (11%); anemia (7%); fatigue (7%); thrombocytopenia (6%); ALT elevation (6%); and neuropathy-sensory (6%). The most common adverse events (all grades) were nausea (50%); fatigue (40%); myalgia (33%); and vomiting (29%). The most severe adverse events (grades 3/4) with GEMZAR for the first-line treatment of patients with pancreatic cancer were neutropenia (24%-26%); alkaline phosphatase elevation (16%-20%); AST elevation (12%-17%); nausea/vomiting (12%-13%); ALT elevation (10%-11%); anemia (10%); leukopenia (9%-10%); thrombocytopenia (8%-10%); bilirubin elevation (4%-8%); and pain (2%-7%). The most common adverse events (all grades) were AST (72%-78%); alkaline phosphatase (71%-77%); anemia (65%-73%); ALT (72%); leukopenia (64%-71%); nausea and vomiting (64%-71%); neutropenia (61%-62%); thrombocytopenia (36%-47%); pain (10%-42%); fever (30%-38%); proteinuria (10%-32%); constipation (10%-31%); diarrhea (24%-30%); rash (24%-28%); and bilirubin (16%-26%).

The most severe adverse events (grades 3/4) with GEMZAR plus cisplatin for the first-line treatment of patients with NSCLC were neutropenia (57%-64%); thrombocytopenia (50%-55%); leukopenia (29%-46%); anemia (22%-25%); nausea (27%); vomiting (23%); nausea/vomiting (39%); neuromotor (12%); hypomagnesemia (7%); neurohearing (6%); creatinine elevation (5%); alopecia (1%-13%); and dyspnea (1%-7%). The most common adverse events (all grades) were paresthesias (38%); hyperglycemia (30%); infection (18%-28%); and constipation (17%-28%).

The most severe adverse events (grades 3/4) with GEMZAR plus carboplatin for the treatment of patients with advanced ovarian cancer were neutropenia (71%), thrombocytopenia (35%), leukopenia (53%), anemia (28%), nausea (6%), vomiting (6%), and constipation (7%). The most common adverse events (all grades) were RBC transfusion (38%), alopecia (49%), neuropathy/sensory (29%), nausea (69%), fatigue (40%), vomiting (46%), diarrhea (25%), and constipation (42%).

See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sections in the accompanying full Prescribing Information for safety and dosing guidelines.

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 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

ALIMTA® (pemetrexed for injection), Lilly GEMZAR® (gemcitabine HCl for injection), Lilly Taxol® (paclitaxel), Bristol-Meyers Squibb Herceptin® (trastuzumab), Genentech

This press release contains forward-looking statements about the potential of GEMZAR for the treatment of breast cancer and reflects Lilly's current beliefs. However, as with any pharmaceutical product under development, there are substantial risks and uncertainties in the process of development, commercialization, and regulatory review. There is no guarantee that the product will receive additional regulatory approvals. There is also no guarantee that the product will continue to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's filing with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

Sánchez-Muñoz A, Dueños-García R, et al. Neoadjuvant chemotherapy with a dose-dense sequential combination of epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine +/- trastuzumab in stage II and III breast cancer. Correlation between pathologic complete response and biologic markers. Abstract #595, American Society of Clinical Oncology (ASCO) Annual Meeting 2007. American Cancer Society, "What Are the Key Statistics for Breast Cancer"," American Cancer Society, www.cancer.org, (May 2, 2007). Pan American Health Organization, "Guidelines for Internatioal Breast Health and Cancer Control," www.paho.org, (March 21, 2006). American Cancer Society, "How is Breast Cancer Staged"," American Cancer Society, www.cancer.org (February 28, 2007).

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