Patients with Adenocarcinoma or Large Cell Carcinoma Histologies Achieved Improvement in Overall Survival when Treated with ALIMTA-based Regimen INDIANAPOLIS, May 28 /PRNewswire-FirstCall/ -- The type of non-small cell lung cancer (NSCLC) patients have may now influence their treatment regimen and, in turn, survival outcome according to the results of a major study published online in the Journal of Clinical Oncology. Publication of the study was announced by Eli Lilly and Company. The 1,725-patient study, the largest Phase III clinical trial in the first-line NSCLC setting, evaluated ALIMTA(R) (pemetrexed for injection) plus cisplatin versus GEMZAR(R) (gemcitabine HCl for injection) plus cisplatin, a standard of treatment in this setting. The trial met its primary endpoint of non-inferiority relative to overall survival. Additionally, in a pre-planned histological analysis, patients with either adenocarcinoma or large-cell carcinoma had a statistically superior and clinically relevant improvement in overall survival when treated with the pemetrexed regimen in the first-line setting. In comparison, patients with squamous cell histology were found to have a more favorable overall survival when treated with the gemcitabine regimen. "While non-small cell lung cancer has typically been treated as one disease, this study confirms that histology, or tumor type, can provide a clue as to which treatment regimen works best for a particular tumor type," said the study's lead author, Giorgio Scagliotti, M.D., Department of Clinical and Biological Sciences Thoracic Oncology Unit, University of Torino, Orbassano, Italy. "If we can tailor the therapy for better results, we are closer to improving outcomes for this terrible disease." The overall survival of patients treated with either the pemetrexed regimen or gemcitabine regimen was found to be non-inferior, with a median survival of 10.3 months. However, when researchers reviewed survival rates according to histological analysis, it was found that patients with adenocarcinoma achieved 12.6 months of overall median survival when treated with the pemetrexed regimen compared to 10.9 months for those treated with the gemcitabine regimen. Patients with large cell carcinoma who were treated with the pemetrexed regimen achieved 10.4 months of overall median survival versus 6.7 months for those treated with the gemcitabine regimen. Both findings are statistically significant. Comparatively, patients with squamous cell histology were found to have a more favorable rate of survival when treated with the gemcitabine regimen, achieving 10.8 months of median survival, compared to the 9.4 months for those treated with the pemetrexed regimen. This finding also was statistically significant. The Phase III, randomized study compared the overall survival between pemetrexed+cisplatin versus gemcitabine+cisplatin in 1,725 chemonaive patients with stage IIIB or IV NSCLC who also exhibited a performance status of 0-1. Patients on the pemetrexed arm (n = 862) were treated with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day one every three weeks for up to six cycles. Patients on the gemcitabine arm (n = 863) were treated with cisplatin (75 mg/m2) on day one and gemcitabine (1250 mg/m2) on days one and eight every three weeks for up to six cycles. Hematologic grade 3/4 drug-related toxicities - neutropenia, anemia and thrombocytopenia - were significantly lower for patients on the pemetrexed arm (p less than or equal to 0.001). Drug-related grade 3/4 febrile neutropenia (p = 0.002) and alopecia (all grades; p < 0.001) were also significantly less on the pemetrexed arm. However, drug-related grade 3/4 nausea (p = 0.004) was more common in patients treated with pemetrexed. Safety data by histology was generally consistent with the overall safety results. "In research, we're always looking for a new door to open - a different way of looking at the problem, in the hope of finding a better solution. That's why this study is so important. It has opened a door that points to histology as a way of helping physicians decide which lung cancer treatment may work best for a particular patient," said Richard Gaynor, M.D., vice president of cancer research and global oncology platform leader at Lilly. Notes to Editor About Non-Small Cell Lung Cancer (NSCLC) NSCLC is the most common type of lung cancer and represents 85 to 90 percent of all lung cancers.(1) NSCLC has five-tier staging, starting at 0 and rising to the severity of stage IV.(2) NSCLC can spread through the lymphatic system, penetrating the chest lining, ribs, and the nerves and blood vessels that lead to the arm. The liver, bones and brain are potential targets if the cancerous cells enter the bloodstream. According to the World Health Organization (WHO) Cancer Report, lung cancer is the world's most common cancer and the leading cause of cancer death for both men and women. More than 1 million people die from lung cancer each year.(3) NSCLC is defined as a group of histologies, that is, tumor types differentiated by cellular structure. The most common NSCLC histology types are squamous (or epidermoid) carcinoma, adenocarcinoma, and large cell carcinoma. These histologies are often classified together because, to date, approaches to diagnosis, staging, prognosis, and treatment have been similar.(4) 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/. (1) American Cancer Society, "What Is Non-Small Cell Lung Cancer?," October 15, 2007, American Cancer Society, http://www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Is_Non- Small_Cell_Lung_Cancer.asp?rnav=cri, (February 21, 2008). (2) American Cancer Society, "How Is Non-Small Cell Lung Cancer Staged?" October 15, 2007, American Cancer Society, http://www.cancer.org/docroot/CRI/content/CRI_2_4_3x_How_Is_Non- Small_Cell_Lung_Cancer_Staged.asp?rnav=cri, (February 21, 2008). (3) World Health Organization, Gender in Lung Cancer and Smoking Research, Department of Gender, Women and Health, 2003, http://www.who.int/gender/documents/en/lungcancerlow.pdf. (4) National Cancer Institute, "Non-Small Cell Lung Cancer Treatment (PDQ(R)) Health Professional Version," December 14, 2007, National Cancer Institute, http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell- lung/HealthProfessional/page2, (February 14, 2008). 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(R) (pemetrexed for injection), Lilly GEMZAR(R) (gemcitabine HCl for injection), Lilly This press release contains forward-looking statements about the potential of ALIMTA and GEMZAR for the treatment of non-small cell lung 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 products will receive additional regulatory approvals. There is also no guarantee that the products will continue to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements. Important Safety Information for ALIMTA Myelosuppression is usually the dose-limiting toxicity with ALIMTA therapy. Contraindication ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed or to any other ingredient used in the formulation. Warnings ALIMTA should not be administered to patients with a creatinine clearance 25% of patients, were AST elevation (72 vs 52, 78); alkaline phosphatase elevation (71 vs 64, 77); anemia (65 vs 45, 73); ALT elevation (72 vs 38, 72); leukopenia (71 vs 15, 64); nausea and vomiting (64 vs 58, 71); neutropenia (62 vs 18, 61); thrombocytopenia (47 vs 15, 36); pain (10 vs 7, 42); fever (30 vs 16, 38); proteinuria (10 vs 2, 32); constipation (10 vs 11, 31); diarrhea (24 vs 31, 30); rash (24 vs 13, 28); and bilirubin elevation (16 vs 25, 26). See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sections in the accompanying full Prescribing Information for safety and dosing guidelines. (Logo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO ) http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE: Eli Lilly and Company CONTACT: Amy Sousa, Lilly, +1-317-276-8478, ; or Neil Hochman, CPR Worldwide, +1-212-453-2067,

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