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.(i)
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.(ii) Researchers at Eli Lilly and Company are actively investigating
the efficacy and safety of lung cancer treatments ALIMTA(R) (pemetrexed for
injection) and GEMZAR(R) (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 chemonaive African-American patients with stage IIIB/IV
NSCLC treated with GEMZAR in combination with carboplatin or paclitaxel
(Taxol(R)) versus patients taking carboplatin in combination with
paclitaxel.(iii) The second study provided data from six previous trials
for non-Caucasian patients with advanced or metastatic NSCLC treated with
ALIMTA.(iv)
"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 lillytrials or
clinicaltrials.
"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 100,000 cells/mm(3) 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
administration 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%); infection 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 sections 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 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
LillyOncology.
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
Taxol(R) (paclitaxel), Bristol-Myers 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.
References
(i) American Cancer Society, "Cancer Still a Heavy Burden for African
Americans," cancer/docroot/NWS/content/NWS_1_1x_Cancer_Still_a_Heavy _Burden_for_African_Americans.asp (April 17, 2007).
(ii) American Cancer Society, "Cancer Facts & Figures for
Hispanics/Latinos 2006-2008," p. 3.
(iii) 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 advanced (Stage IIB, IV) non-small cell lung cancer (Alpha
Oncology trial A1-99002L). American Society of Clinical Oncology (ASCO)
Annual Meeting 2007.
(iv) Obasaju CK, Kulkarni P, Wang Y, et al. Effect of race on the
safety and efficacy of pemetrexed therapy in locally advanced and
metastatic non- small cell lung cancer (NSCLC). American Society of
Clinical Oncology (ASCO) Annual Meeting 2007.
Eli Lilly and Company
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