Lilly Studies Try to Shed Light on Impact of Race on Lung Cancer Treatment
June 01 2007 - 2:00PM
PR Newswire (US)
Company Launches 1,000-Patient Lung Cancer Diversity Study CHICAGO,
June 1 /PRNewswire-FirstCall/ -- 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 http://www.lillytrials.com/ or
http://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 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 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 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. (i) 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). (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.
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Hochman, CPR Worldwide, +1-212-453-2067, or mobile,
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