Study Highlights Quality-of-Life Data CHICAGO, June 2
/PRNewswire-FirstCall/ -- ALIMTA(R) (pemetrexed for injection)
showed additional utility in the treatment of the most diagnosed
type of cancer(i), according to data presented today at the 43rd
Annual Meeting of the American Society of Clinical Oncology (ASCO).
Results from a Phase III study suggest that a first-line
ALIMTA-based regimen may deliver less toxicity than a commonly used
therapy in advanced non-small cell lung cancer (NSCLC). ALIMTA is
manufactured and marketed by Eli Lilly and Company. A prospective,
randomized, multicenter Phase III study was conducted to compare
ALIMTA plus carboplatin with the commonly used regimen of GEMZAR(R)
(gemcitabine HC1 for injection) plus carboplatin (ASCO Abstract #
7517(ii)). The study, conducted by the Norwegian Lung Cancer Group,
enrolled 446 chemonaive patients with either stage IIIB or IV
NSCLC. The primary purpose of the study was to evaluate if the
ALIMTA-carboplatin combination provided increased quality-of-life
benefits while offering comparable survival data. As such, the
primary endpoint was quality of life (defined in the study as
nausea/vomiting; dyspnea or a difficulty in breathing, and;
fatigue) and the secondary endpoint was overall survival. Thus far,
384 patients have been analyzed for toxicity and there were fewer
patients in the ALIMTA arm who experienced Grade 3/4
thrombocytopenia or a low platelet level (48 vs. 107, p < .001);
leukopenia or a lowering of leukocyte white blood cells (44 vs. 89,
p < .001), and; granulocytopenia or a lowering of granulocyte
white blood cells (78 vs. 98, p=.02). More patients in the GEMZAR
arm received transfusion of platelets (5 vs. 19, p=.02). At this
point, no difference in survival has been observed. "The patients
in this study received a comparable quality-of-life benefit whether
they received ALIMTA and carboplatin or GEMZAR and carboplatin,"
said Bjorn Henning Gronberg, M.D. of St. Olavs University Hospital
in Norway and the study's principal investigator. "Patients on the
ALIMTA arm also appeared to benefit from a lower toxicity profile."
Additional data to be presented on Sunday, June 3rd at ASCO from a
Phase II, open-label, non-randomized trial will report on an
International Oncology Network Study evaluating the safety of a
triplet therapy in which bevacizumab (Avastin(R)) was added to the
combination of ALIMTA plus oxaliplatin (Eloxatin(R)) in patients
with advanced NSCLC (Abstract # 7700(iii)). Previous research has
indicated that oxaliplatin and ALIMTA, as single agents, have shown
activity in NSCLC, and ALIMTA has shown synergistic effects when
combined with platinum-based drugs.(iv,v) This preliminary study
was conducted to evaluate the efficacy and safety of the
combination as first-line treatment for NSCLC. "We are pleased to
see that ALIMTA has a synergistic effect with platinum agents like
carboplatin," said Richard Gaynor, M.D., vice president, cancer
research and global oncology platform leader for Lilly. "We look
forward to continued research on ALIMTA as a chemotherapeutic
foundation with targeted therapies and other anti-cancer agents for
the treatment of lung cancer. "Lilly is aggressively investigating
potential novel therapies in other tumor types, as we are committed
to providing patients with therapeutic options that fight the
cancer but do not compromise quality of life." Lilly also has
studied ALIMTA plus cisplatin for the first-line treatment of
NSCLC. In the first quarter of 2007, a study of ALIMTA plus
cisplatin versus GEMZAR plus cisplatin met its primary endpoint of
non-inferiority relative to overall survival. Utilizing these data,
Lilly plans to submit ALIMTA for an indication for the first-line
treatment of NSCLC to the European Medicines Agency (EMEA) later
this year. At ASCO, researchers will also present data that show
ALIMTA as a chemotherapeutic foundation to a variety of approved
and investigational targeted anti-cancer agents, including
bevacizumab (Avastin(R)), erlotinib (Tarceva(R)), cetuximab
(Erbitux(R)) and vandetanib (Zactima(TM)). ALIMTA is an antifolate
which interferes with a crucial process that allows cancer cells to
reproduce and spread. The most common side effects when ALIMTA is
used as monotherapy are disorders of the blood and lymphatic
system, gastrointestinal disorders, fatigue, rash and desquamation
or flaking of skin in scales. Myelosuppression is usually the
dose-limiting toxicity with ALIMTA therapy. About Non-Small Cell
Lung Cancer NSCLC is the most common type of lung cancer and
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 performed on all
patients receiving ALIMTA. Patients should not begin a new cycle of
treatment unless the ANC is 1500 cells/mm3, the platelet count is
> 100,000 cells/mm3 and creatinine clearance greater than or
equal to 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 bevacizumab (Avastin(R)), Genentech oxaliplatin
(Eloxatin(R)), Sanofi Aventis erlotinib (Tarceva(R)), Genentech,
OSI Pharmaceuticals cetuximab (Erbitux(R)), Bristol-Myers Squibb,
ImClone, Merck vandetanib (Zactima(TM)), AstraZeneca 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) Parkin DM, Bray F, Ferlay J,
Pisani P, Global Cancer Statistics, 2002. CA Cancer J Clin
2005;55;74-108. (ii) Gronberg, BH. Pemetrexed+carboplatin vs.
gemcitabine+carboplatin in the treatment of stage IIIB/IV non-small
cell lung cancer. Abstract #7517, American Society of Clinical
Oncology (ASCO) Annual Meeting 2007. (iii) Heist RS, Auerbach M, et
al. Phase II trial of oxaliplatin, pemetrexed, and bevacizumab in
previously-treated advanced non-small cell lung cancer (NSCLC).
Abstract #7700, American Society of Clinical Oncology (ASCO) Annual
Meeting 2007. (iv) Scagliotti GV, Kortsik C, Dark GG, et al.
Pemetrexed combined with oxaliplatin or carboplatin as first-line
treatment in advanced non- small cell lung cancer: a multicenter,
randomized, phase II trial. Clin Cancer Res. 2005 Jan 15;11 (2 Pt
1):690-6. (v) Zinner RG, Fossella FV, Gladish GW, et al. Phase II
study of pemetrexed in combination with carboplatin in the
first-line treatment of advanced nonsmall cell lung cancer. Cancer.
2005 Dec 1;104(11):2449-56. (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
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Eli Lilly and Company CONTACT: Gregory L. Clarke of Lilly,
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