CHICAGO, June 1, 2007 -- Statistics show lung cancer is the leading cause of cancer death in African-Americans, with 21,550 new cases expected to be diagnosed and 16,700 deaths expected this year. Equally devastating, lung cancer is the leading cause of cancer death in Hispanic men and the second leading cause of cancer death in Hispanic women. Researchers at Eli Lilly and Company are actively investigating the efficacy and safety of lung cancer treatments ALIMTA® (pemetrexed for injection) and GEMZAR® (gemcitabine HCl for injection) in treating non-small cell lung cancer (NSCLC) in African-Americans, Hispanics and other diverse populations.
Two retrospective Lilly studies were unveiled today at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill. They offered cursory insight into how a diverse group of patients respond to treatment with Lilly chemotherapeutic options. One study analyzed data of chemonaïve African-American patients with stage IIIB/IV NSCLC treated with GEMZAR in combination with carboplatin or paclitaxel (Taxol®) versus patients taking carboplatin in combination with paclitaxel. The second study provided data from six previous trials for non-Caucasian patients with advanced or metastatic NSCLC treated with ALIMTA.
“African-Americans are often underrepresented in clinical trials and, therefore, little is known about the possible impact of race on the utility of many medications,” said Coleman Obasaju, M.D., Ph.D., United States oncology medical director of Lilly and the principal investigator of these two studies. “Because lung cancer is a particularly devastating disease, and a growing concern in the African-American population, it was a logical starting point for our analysis.”
The GEMZAR study released at ASCO analyzed overall survival data from a previous randomized Phase III trial in the treatment of NSCLC, viewing data outcomes and toxicity data of 128 African-Americans compared with 906 Caucasians. The trial was designed to compare the efficacy of GEMZAR plus carboplatin with GEMZAR plus paclitaxel and a reference regimen of carboplatin plus paclitaxel. Data from all three arms were pooled for this analysis. Overall survival, the primary endpoint, on the African-American arm was 8.7 months compared to 8.1 months in the Caucasian arm, which was not significantly different. African-Americans demonstrated slightly lower incidences of grade 3/4 toxicities (constitutional, hemorrhagic and metabolic).
The ALIMTA study reviewed a post-hoc analysis of pooled data from six previous trials, including one Phase III in a second-line setting and five Phase II trials in a first-line setting. Patients with Stage IIIB/IV NSCLC were given at least one dose of ALIMTA (single-agent or in combination with other treatments) every 21 days. The trial evaluated results from 411 Caucasian patients compared with 117 non-Caucasian (African-American, Asian and Hispanic) patients. Based on this analysis, race did not have a statistically significant impact on efficacy parameters (response rate, survival and disease control rate). Non-Caucasian patients had lower grade 3/4 toxicities, including neutropenia (a decrease in white blood cells); anemia (a decrease in red blood cells); fatigue; and nausea.
“At the very least, the data unveiled today suggests that we should continue actively studying the impact of our medications on a diverse number of populations,” said Dr. Obasaju.
To that end, Lilly recently began enrollment into what may be the largest and most diverse Phase III study in NSCLC. The study will evaluate ALIMTA in 1,000 patients with NSCLC. Enrollment will include 200 African-Americans, 200 Asians, 200 Hispanics and 400 Caucasians. For more information on this trial visit www.lillytrials.com or www.clinicaltrials.gov.
“Scientific reasoning tells us that because of genetic differences, patients with similar tumors may respond differently to specific treatment regimens,” said Richard Gaynor, M.D., vice president, cancer research and global oncology platform leader at Lilly. “Ultimately, our goal is to ensure that we offer the optimal outcome to each and every patient.”
About Non-Small Cell Lung Cancer
The most common type of lung cancer, non-small cell lung cancer (NSCLC) represents 75-80 percent of all lung cancers. NSCLC has five-tier staging, starting at 0 and rising to the severity of stage IV. 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 blood stream.
ALIMTA Indications
ALIMTA in combination with cisplatin is indicated for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.
ALIMTA as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after prior chemotherapy. The effectiveness of ALIMTA in second-line NSCLC was based on the surrogate endpoint, response rate. There are no controlled trials demonstrating a clinical benefit, such as a favorable survival effect or improvement of disease-related symptoms.
Important Safety Information
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 <45 mL/min. One patient with severe renal impairment (creatinine clearance 19 mL/min) who did not receive folic acid and vitamin B12 died of drug-related toxicity following administration of ALIMTA alone.
ALIMTA can suppress bone marrow function, as manifested by neutropenia, thrombocytopenia, and anemia (or pancytopenia).
Patients must be instructed to take folic acid and vitamin B12 with ALIMTA as a prophylaxis to reduce treatment-related hematologic and GI toxicities.
Pregnancy Category D—ALIMTA may cause fetal harm when administered to a pregnant woman.
Precautions
Complete blood cell counts, including platelet counts and periodic chemistry tests, should be per-formed on all patients receiving ALIMTA.
Patients should not begin a new cycle of treatment unless the ANC is 1500 cells/mm3, the plate-let count is >100,000 cells/mm3 and creatinine clearance = 45 mL/min.
Pretreatment with dexamethasone or its equivalent has been reported to reduce the incidence and severity of skin rash.
The effect of third space fluid, such as pleural effusion and Ascites on ALIMTA is unknown.
In patients with clinically significant third space fluid, consideration should be given to draining the effusion prior to ALIMTA administration.
Caution should be used when administering ibuprofen concurrently with ALIMTA to patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 mL/min). Patients with mild to moderate renal insufficiency should avoid taking NSAIDs with short elimination half-lives for a period of 2 days before, the day of, and 2 days following administration of ALIMTA. In the absence of data regarding potential interaction between ALIMTA and NSAIDs with longer half-lives, all patients taking these NSAIDs should interrupt dosing for at least 5 days before, the day of, and 2 days following ALIMTA administration. If concomitant admini-stration of an NSAID is necessary, patients should be monitored closely for toxicity, especially myelosuppression, renal and gastrointestinal toxicities.
Concomitant administration of nephrotoxic drugs or substances that are tubularly secreted could result in delayed clearance of ALIMTA.
It is recommended that nursing be discontinued if the mother is being treated with ALIMTA.
ALIMTA should be administered under the supervision of a qualified physician experienced in the use of antineoplastic agents.
Dose adjustments may be necessary in patients with hepatic insufficiency.
Dosing and Modification Guidelines
Dose adjustments at the start of a subsequent cycle should be based on nadir hematologic counts or maximum nonhematologic toxicity from the preceding cycle of therapy. Modify or suspend therapy according to the Dosage Reduction Guidelines in the full Prescribing Information.
Adverse Events
The most common adverse events (grades 3/4) with ALIMTA in combination with cisplatin for the treatment of patients with MPM were neutropenia (24%); leukopenia (16%); anemia (6%); thrombocytopenia (5%); infection without neutropenia (2%); fatigue (17%); thrombsis/embolism 6%); nausea (12%); vomiting (11%); dyspnea (11%); and chest pain (9%). The most common clinically relevant adverse events (all grades) were fatigue (80%); thrombosis/embolism (7%); nausea (84%); vomiting (58%); constipation (44%); anorexia (35%); stomatitis/pharyngitis (28%); diarrhea (26%); dyspnea (66%); chest pain (40%); and rash (22%).
The most common adverse events (grades 3/4) with ALIMTA for the treatment of patients with NSCLC were anemia (8%); leukopenia (5%); neutropenia (5%); thrombocytopenia (2%); infec-tion without neutropenia (6%); fatigue (16%); thrombosis/embolism (3%); cardiac ischemia (3%);anorexia (5%); dyspnea (18%); and chest pain (7%). The most common clinically relevant adverse events (all grades) were fatigue (87%); anorexia (62%); nausea (39%); constipation (30%); vomiting (25%); diarrhea (21%); stomatitis/pharyngitis (20%); dyspnea (72%); chest pain (38%); neuropathy/sensory (29%); infection without neutropenia (23%); and rash (17%).
See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sec-tions in the accompanying full Prescribing Information for safety and dosing guidelines.
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 indi-cated for patients previously treated with 5-FU.
GEMZAR in combination with carboplatin is indicated for the treatment of patients with ad-vanced 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 meas-ures 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 discon-tinuation 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. Administra-tion 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 radia-tion 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 experi-enced 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 phos-phatase 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%); leu-kopenia (64%-71%); nausea and vomiting (64%-71%); neutropenia (61%-62%); thrombocyto-penia (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%), leuko-penia (53%), anemia (28%), nausea (6%), vomiting (6%), and constipation (7%). The most common adverse events (all grades) were RBC transfusion (38%), alopecia (49%), neuropa-thy/sensory (29%), nausea (69%), fatigue (40%), vomiting (46%), diarrhea (25%), and constipa-tion (42%).
See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sec-tions 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
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 products 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 filing with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.
American Cancer Society, “Cancer Still a Heavy Burden for African Americans,” http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Cancer_Still_a_Heavy_Burden_for_African_Americans.asp (April 17, 2007). American Cancer Society, “Cancer Facts & Figures for Hispanics/Latinos 2006-2008,” p. 3. Obasaju CK, Gonin R, Catalano RB, et al. Subgroup analysis of African American patients from a randomized Phase 3 trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in ad-vanced (Stage IIB, IV) non-small cell lung cancer (Alpha Oncology trial A1-99002L). American Society of Clinical Oncology (ASCO) Annual Meeting 2007.