ASCO Study Confirms Importance of Histology in Treatment of Non-Small Cell Lung Cancer With ALIMTA (pemetrexed for injection)
16 May 2008 - 11:00AM
PR Newswire (US)
INDIANAPOLIS, May 15 /PRNewswire-FirstCall/ -- Lung cancer patients
whose histology is factored into treatment decisions may fare
better as a result, according to data from a pivotal non-small cell
lung cancer (NSCLC) clinical trial. Data from the trial, which
involved Eli Lilly and Company's ALIMTA(R) (pemetrexed for
injection), will be presented at the 44th Annual Meeting of the
American Society of Clinical Oncology (ASCO) in Chicago, Ill., May
30 -- June 3, 2008. "The data presented at ASCO confirms that
histology matters when treating non-small cell lung cancer," said
Richard Gaynor, M.D., vice president, cancer research and global
oncology platform leader for Lilly. "We are seeing continued
affirmation that when physicians factor in a patient's histology,
pemetrexed becomes an even more valuable treatment option in
non-small cell lung cancer." Results from a multicenter,
double-blind Phase III trial will be presented on June 2, 2008, at
ASCO (Abstract # 8011). The study also was one of those featured
during ASCO's live online presscast, a virtual press event that
marked the first time researchers were invited to present key
abstracts to the media prior to the annual meeting. The trial
compared the efficacy and safety of pemetrexed versus a placebo in
663 patients with stage IIIB/IV NSCLC whose disease had not
progressed after four cycles of platinum-based induction
chemotherapy. According to the results, patients treated with
pemetrexed demonstrated increased efficacy with respect to
progression-free survival compared to those treated by placebo (4.3
months vs. 2.6 months), and pemetrexed patients also achieved
better tumor response (p < 0.001). However, when data was broken
down by histology, it was comparable to previous pemetrexed trials
evaluating histology -- patients with a non-squamous histology
fared better than those with a squamous histology. Patients with
non-squamous histology who were treated with pemetrexed achieved
4.5 months of median progression-free survival compared to 2.8
months for patients with squamous histology. "The efficacy findings
of this data show that pemetrexed performed better in patients with
non-squamous histology for the treatment of non-small cell lung
cancer," said the trial's lead investigator, Tudor Ciuleanu, M.D.
of the Institutul Oncologi I Chiricuta in Cluj, Romania. Patients
in the trial were treated with pemetrexed (500 mg/m2) plus best
supportive care or placebo plus best supportive care. All patients
were supplemented with vitamin B12, folic acid and dexamethasone.
No significant toxicity differences were identified between the two
trial arms with the exception of grade 3/4 anemia (pemetrexed 4.5%,
placebo 1.4%) and total serious adverse events due to the treatment
(pemetrexed 4.3%, placebo 0%). The data presented at ASCO
reaffirmed findings from previous studies, most notably a Phase III
study of pemetrexed plus cisplatin versus gemcitabine plus
cisplatin in chemonaive patients with locally advanced or
metastatic NSCLC. That study showed NSCLC patients with a
non-squamous histology (those with adenocarcinoma or large cell
carcinoma) demonstrated increased benefits when treated with
pemetrexed(1). 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(2). NSCLC has five-tier
staging, starting at 0 and rising to the severity of stage IV(3).
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(4). 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(5). About Lilly
Oncology, a Division of Eli Lilly and Company For more than four
decades, Lilly Oncology has been dedicated to delivering innovative
solutions that improve the care of people living with cancer.
Because no two cancer patients are alike, Lilly Oncology is
committed to developing novel treatment approaches. Our quest is to
develop a broad portfolio of tailored therapies that accelerate the
pace and progress of cancer care. 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. ALIMTA(R)
(pemetrexed for injection), Lilly P-LLY This press release contains
forward-looking statements about the potential of ALIMTA 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 product will receive additional
regulatory approvals. There is also no guarantee that the product
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 < 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 greater
than or equal to 1500 cells/mm3 and the platelet count is greater
than or equal to 100,000 cells/mm3 and creatinine clearance is
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.
Concomitant administration of nephrotoxic drugs or substances that
are tubularly secreted could result in delayed clearance of ALIMTA.
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. 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. Abbreviated Adverse Events (%
incidence) The most common adverse events (grades 3/4) with ALIMTA
versus docetaxel, respectively, for the treatment of patients with
NSCLC were anemia (8 vs 7); leukopenia (5 vs 28); neutropenia (5 vs
40); thrombocytopenia (2 vs 1); ALT elevation (3 vs 1); febrile
neutropenia (2 vs 13); infection without neutropenia (6 vs 4);
infection/febrile neutropenia -- other (2 vs 1); fatigue (16 vs
17); thrombosis/embolism (3 vs 3); cardiac ischemia (3 vs 1);
anorexia (5 vs 8); dyspnea (18 vs 26); and chest pain (7 vs 8). The
most common clinically relevant adverse events (all grades) with
ALIMTA versus docetaxel, respectively, were fatigue (87 vs 81);
anorexia (62 vs 58); nausea (39 vs 25); constipation (30 vs 23);
vomiting (25 vs 19); diarrhea (21 vs 34); stomatitis/pharyngitis
(20 vs 23); edema (19 vs 24); dyspnea (72 vs 74); chest pain (38 vs
32); neuropathy/sensory (29 vs 32); infection without neutropenia
(23 vs 17); anemia (33 vs 33); fever (26 vs 19); and rash (17 vs
9). The most common adverse events (grades 3/4) with ALIMTA in
combination with cisplatin versus cisplatin alone, respectively,
for the treatment of patients with MPM were neutropenia (24 vs 4);
leukopenia (16 vs 1); anemia (6 vs 0); thrombocytopenia (5 vs 0);
infection without neutropenia (2 vs 0); infection with grade 3/4
neutropenia (1 vs 0); infection/febrile neutropenia -- other (1 vs
0); febrile neutropenia (1 vs 0); fatigue (17 vs 13);
thrombosis/embolism (6 vs 4); nausea (12 vs 6); vomiting (11 vs 5);
dyspnea (11 vs 7); and chest pain (9 vs 6). The most common
clinically relevant adverse events (all grades) with ALIMTA in
combination with cisplatin versus cisplatin alone, respectively,
were neutropenia (58 vs 16); leukopenia (55 vs 20); anemia (33 vs
14); thrombocytopenia (27 vs 10); fatigue (80 vs 74);
thrombosis/embolism (7 vs 4); nausea (84 vs 79); vomiting (58 vs
52); constipation (44 vs 39); anorexia (35 vs 25);
stomatitis/pharyngitis (28 vs 9); diarrhea (26 vs 16); dyspnea (66
vs 62); chest pain (40 vs 30); and rash (22 vs 9). See complete
Warnings, Precautions, Adverse Reactions, and Dosage and
Administration sections in the full Prescribing Information for
safety and dosing guidelines. (1) Scagliotti G, Purvish P, et al.
Phase III study of pemetrexed plus cisplatin versus gemcitabine
plus cisplatin in chemonaive patients with locally advanced or
metastatic non-small cell lung cancer (NSCLC). Abstract PRS-3, 12th
World Conference on Lung Cancer (WCLC) 2007. Journal of Thoracic
Oncology, Vol 2 No 8, Supplement 4, Page S306, August 2007. (2)
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). (3)
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).
(4) 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 . (5)
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). (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 of Eli Lilly and Company,
office, +1-317-276-8478, mobile, +1-317-997-1481, ; or Neil Hochman
of CPR Worldwide, office, +1-212-453-2067, or mobile,
+1-516-784-9089,
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