Efficacy

Superior outcomes with 1st-line therapy in MBC

Overall Response Rate
Overall Response Rate by Location and Age
Superior TTP - A Durable Response

Overall Response Rate
First-line GEMZAR therapy (GEMZAR plus paclitaxel) demonstrated superior treatment outcomes compared with paclitaxel alone in a Phase III metastatic breast cancer study.

85% improvement in overall response rate.

Overall survival
There was a strong trend toward improved survival for the group given GEMZAR, based on an interim survival analysis.

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Overall Response Rate by Location and Age
Retrospective subset analysis from the Phase III registration trial.

RR in patients with nonvisceral disease only at baseline

* No visceral involvement.

RR in patients with visceral disease at baseline

† May also have had nonvisceral involvement.

Lung and liver (RR) analysis (percentages)

‡ Includes pleural effusion, pleura, and pleural fluid.

Data represent a retrospective subset analysis from the registration study. Statistical significance is not implied in the subset analysis shown. Subgroup analyses can be limited by various factors (e.g., decreased statistical power, increased variance, multiplicity) that may limit the conclusions regarding statistical inference and clinical benefit seen from treatment.

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Retrospective subset analysis from the phase III registration trial.

Data represent a retrospective subset analysis from the registration study. Statistical significance is not implied in the subset analysis shown. Subgroup analyses can be limited by various factors (eg, decreased statistical power, increased variance, multiplicity) that may limit the conclusions regarding statistical inference and clinical benefit seen from treatment.

* From a single-agent safety database of 979 patients, grades 3/4 thrombocytopenia was more common in the elderly.

Retrospective subset analysis from the phase III registration trial.
Best change from baseline^† for patients with a best overall response of stable disease,^‡ partial response, or complete response.

Of the 267 patients in the GEMZAR plus paclitaxel arm, 196 (73%) had a best overall response of stable disease,^‡ partial response, or complete response.

Of the 262 patients in the paclitaxel arm, 155 (59%) had a best overall response of stable disease,^† partial response, or complete response.

† Investigator-assessed measurements. Note that 2 patients in the paclitaxel arm with stable disease did not have post-baseline investigator-assessed measurements.
‡ Stable disease: No change of disease (this includes an increase of <25% or a decrease of <50%).

Retrospective subset analysis from the phase III registration trial.

Data represent a retrospective subset analysis from the registration study. Statistical significance is not implied in the subset analysis shown. Subgroup analyses can be limited by various factors (eg, decreased statistical power, increased variance, multiplicity) that may limit the conclusions regarding statistical inference and clinical benefit seen from treatment.

* Anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.

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Superior TTP — A Durable Response
Patients receiving GEMZAR therapy* achieved longer time to disease progression (TTP) over paclitaxel alone.

Median time to disease progression (TTP)

79% improvement in TTP.

* GEMZAR combined with paclitaxel.

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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.

Myelosuppression is usually the dose-limiting toxicity with GEMZAR therapy.
See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sections in the accompanying full Prescribing Information for safety and dosing guidelines.

Reference:

Data on file, Eli Lilly and Company; 1a: ONC20060214B; 1b: ONC20060214C; 1c: ONC20070801A; 1d: ONC20070801B; 1e: ONC20060214E.

©2008 Eli Lilly and Company. All Rights Reserved. This site is intended for use by healthcare professionals in the United States only.
GEMZAR^® is a registered trademark of Eli Lilly and Company. GC 50579

About GEMZAR

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 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.

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.

Important Safety Information

Myelosuppression is usually the dose-limiting toxicity with GEMZAR therapy.

Contraindication
Known hypersensitivity to GEMZAR.

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. 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.

Abbreviated Adverse Events (% incidence)
The most severe adverse events (grades 3/4) with GEMZAR plus cisplatin for the first-line treatment of patients with NSCLC in comparative trials of a 28-day regimen (GEMZAR plus cisplatin versus cisplatin alone) and a 21-day regimen (GEMZAR plus cisplatin versus etoposide plus cisplatin), respectively, were neutropenia (57 vs 4, 64 vs 76); thrombocytopenia (50 vs 4, 55 vs 13); leukopenia (46 vs 3, 29 vs 43); anemia (25 vs 7, 22 vs 15); nausea 28d (27 vs 21); vomiting 28d (23 vs 19); nausea/vomiting 21d (39 vs 26); neuromotor 28d (12 vs 3); hypomagnesemia 28d (7 vs 2); neurohearing 28d (6 vs 6); creatinine elevation 28d (5 vs 3); and dyspnea (7 vs 5, 1 vs 0). The most common adverse events (all grades) of the 28-day regimen (GEMZAR plus cisplatin versus cisplatin alone) and the 21-day regimen (GEMZAR plus cisplatin versus etoposide plus cisplatin), respectively, were anemia (89 vs 67, 88 vs 77); leukopenia (82 vs 25, 86 vs 87); neutropenia (79 vs 20, 88 vs 87), thrombocytopenia (85 vs 13, 81 vs 45), lymphocytopenia 28d (75 vs 51); hematuria (15 vs 13, 22 vs 10); creatinine 28d (38 vs 31), hyperglycemia 28d (30 vs 23); hypomagnesemia 28d (30 vs 17); nausea 28d (93 vs 87); vomiting 28d (78 vs 71); nausea and vomiting 21d (96 vs 86); alopecia (53 vs 33, 77 vs 92); neuromotor 28d (35 vs 15); constipation (28 vs 21, 17 vs 15); neurohearing 28d (25 vs 21); paresthesias 21d (38 vs 16); and infection (18 vs 12, 28 vs 21).

The most severe adverse events (grades 3/4) with GEMZAR plus carboplatin versus carboplatin, respectively, for the treatment of patients with advanced ovarian cancer were neutropenia (71 vs 12), thrombocytopenia (35 vs 11), leukopenia (53 vs 7), anemia (28 vs 11), nausea (6 vs 3), vomiting (6 vs 3), and constipation (7 vs 3). The most common adverse events (all grades) were neutropenia (90 vs 58); leukopenia (86 vs 70); anemia (86 vs 75); and thrombocytopenia (78 vs 57); RBC transfusion (38 vs 15), alopecia (49 vs 17), neuropathy/sensory (29 vs 27), nausea (69 vs 61), fatigue (40 vs 32), vomiting (46 vs 36), diarrhea (25 vs 14), and constipation (42 vs 37).

The most severe adverse events (grades 3/4) with GEMZAR plus paclitaxel versus paclitaxel, respectively, for the treatment of patients with MBC were neutropenia (48 vs 11); alopecia (18 vs 22); leukopenia (11 vs 2); anemia (7 vs 4); fatigue (7 vs 2); thrombocytopenia (6 vs 2); ALT elevation (6 vs 1); and neuropathy-sensory (6 vs 3). The most common adverse events (all grades) were alopecia (90 vs 92); anemia (69 vs 51); neutropenia (69 vs 31); neuropathy-sensory (64 vs 58); nausea (50 vs 31); fatigue (40 vs 28); myalgia (33 vs 33); vomiting (29 vs 15); and thrombocytopenia (26 vs 7).

The most severe adverse events (grades 3/4) with GEMZAR versus 5-FU for the first-line treatment of patients with pancreatic cancer and data reported from a single agent safety database, respectively, were neutropenia (26 vs 5, 24); alkaline phosphatase elevation (16 vs 17, 20); AST elevation (12 vs 2, 17); nausea/vomiting (13 vs 5, 12); ALT elevation (10 vs 0, 11); anemia (10 vs 0, 10); leukopenia (10 vs 2, 9); thrombocytopenia (10 vs 2, 8); bilirubin elevation (4 vs 9, 8); and pain (2 vs 0, 7). The most common adverse events (all grades), defined as reported in > 25% of patients, were AST elevation (72 vs 52, 78); alkaline phosphatase elevation (71 vs 64, 77); anemia (65 vs 45, 73); ALT elevation (72 vs 38, 72); leukopenia (71 vs 15, 64); nausea and vomiting (64 vs 58, 71); neutropenia (62 vs 18, 61); thrombocytopenia (47 vs 15, 36); pain (10 vs 7, 42); fever (30 vs 16, 38); proteinuria (10 vs 2, 32); constipation (10 vs 11, 31); diarrhea (24 vs 31, 30); rash (24 vs 13, 28); and bilirubin elevation (16 vs 25, 26).

See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information for safety and dosing guidelines.

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