Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Recurrence

Disease Progression

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Pemetrexed

Docetaxel

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Tyrosine

500mg/m2 / 3 weeks (Alimta) or 75mg/m2 / 3 weeks (Taxotere)

Alimta or Taxotere

erlotinib [Tarceva]

Clinical Trials

This 2 arm study will evaluate the efficacy, safety, and pharmacokinetics of Tarceva and that of standard of care chemotherapy in patients with advanced, recurrent, or metastatic NSCLC experiencing disease progression after failure of platinum-based chemotherapy.Eligible patients will be randomized to receive either Tarceva 150mg po daily, or comparator (either Alimta 500mg/m2 every 3 weeks, or Taxotere 75mg/m2 every 3 weeks). The anticipated time on study treatment is until disease progression ,and the target sample size is 500+ individuals.

A Study of Tarceva (Erlotinib) and Standard of Care Chemotherapy in Patients With Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer (NSCLC)

An Open-label, Randomized Study to Evaluate the Effect of Tarceva, Compared With Alimta (Pemetrexed) or Taxotere (Docetaxel),on Survival in Patients With Advanced, Recurrent or Metastatic Non-small Cell Lung Cancer Who Have Experienced Disease Progression During Platinum-based Chemotherapy

Overall survival (OS) was determined from the date of randomization to the date of death irrespective of the cause of death.

OS was determined from the date of randomization to the date of death irrespective of the cause of death. Kaplan-Meier estimates were used for analysis.

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by immunohistochemistry (IHC). OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis.

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis.

Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.0). Progressive Disease was defined as at least a 20 percent (%) increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The primary analysis of PFS used objective progression (RECIST) plus clinical progression (based on relevant clinical findings - if any). A further assessment of PFS was made on objective (radiological) progression. If clinical progression was diagnosed first, the participant was censored at the date of the last tumor assessment, where non-progression was documented.

Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy.

Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Event free estimates were determined using Kaplan-Meier estimates.

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC.Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease was defined as At least a 20 % increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first in EGFR positive and negative populations. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Kaplan-Meier estimates were used for analysis.

EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. Tumor response was evaluated according to RECIST criteria (version 1.0). PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first in EGFR positive and negative populations. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Event free estimates were determined using Kaplan-Meier estimates.

Best overall response was defined as the best response according to RECIST recorded from the date of randomization until disease progression or recurrence. CR: disappearance of all target lesions; PR: reduction by at least 30% of the sum of the longest diameters of each target lesion, taking the initial sum of the longest diameters as a reference; Stable disease (SD): insufficient tumor reduction to define partial response and/or tumor increase less than that necessary to define tumor progression, taking as a reference the smallest sum of the longest diameter since the start of treatment; Progressive Disease (PD): increase by at least 20% in the sum of LD of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. 95% Confidence Interval (CI) for one sample binomial using Pearson-Clopper method. Participants with a missing response were considered non-responders.

The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the Functional Assessment of Cancer Treatment-General scale (FACT-G) and the lung cancer subscale (LCS). The FACT-L total score ranges from 0 to 136, higher scores represent better QOL.

The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the FACT-G and the LCS. The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Time to deterioration of QoL or symptom progression is defined as time from randomization until either a clinically meaningful decline from baseline in Total FACT-L or, death on study, whichever occurs first. The clinically meaningful decline that was used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment. Kaplan-Meier estimate was used to determine time to event.

The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the FACT-G and the LCS. The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Kaplan Meier estimates were used for analysis.

Participants' responses on the FACT-L were scored according to the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline.

Participants' responses on the FACT-L were scored according to FACIT measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline. Kaplan Meier estimated were used for analysis.

TOI is defined as the sum of the scores of the Physical Well- Being (PWB), Functional Well-Being (FWB), and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline.

TOI is defined as the sum of the scores of the PW, FWB, and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6- point decline from baseline. Kaplan-Meier estimates were used for analysis.

TOI is defined as the sum of the scores of the PW, FWB, and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. The clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline. Kaplan-Meier estimates were used for analysis.

Hoffmann-La Roche

All participants who received at least one dose of the trial medication and had at least one safety follow-up, whether withdrawn prematurely or not, were included in the safety analysis population (SAP).

Participants received either Alimta 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or Taxotere 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, Taxotere was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.

Comparator

Participants received a single oral dose of erlotinib 150 mg/day until disease progression, unacceptable toxicity or death.

Erlotinib

Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.

Participants received erlotinib, 150 mg, administered orally as a tablet, once daily until disease progression, unacceptable toxicity, or death.

Total

Age, Continuous

Sex: Female, Male

Full Analysis Set (FAS): All participants randomized were included according to the therapy that they were randomized to receive in the FAS population.

Medical Communications

Percentage of Participants Who Died (All Participants; Data Cutoff: 07 September 2010)

Duration of Overall Survival in All Participants (Data Cutoff 07 September 2010)

Probable Percentage of Participants Remaining Alive at 1 Year

EGFR Positive (n=149,143)

EGFR Negative (n=39,32)

FAS population; Only participants with confirmed presence or absence of EGFR were included in the analysis. number (n) equals (=) number of participants who were EGFR positive or negative

Percentage of Participants Who Died in Epidermal Growth Factor Receptor (EGFR) Positive and Negative Population

FAS population; Only participants with confirmed presence or absence of EGFR were included in the analysis. n=number of participants who were EGFR positive or negative

Duration of OS in EGFR Positive and Negative Population

EGFR Positive (n=30,32)

EGFR Negative (n=8,4)

Participants received either pemetrexed 500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel l75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.

FAS population; n=number of EGFR positive or negative participants remaining at risk

Probable Percentage of Participants Remaining Alive at 1 Year in the EGFR Positive and Negative Population

Percentage of Participants With Disease Progression or Death (All Participants; Data Cut Off 07 September 2010)

Progression-Free Survival (PFS) in All Participants (Data Cutoff 07 September 2010)

Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months

Percentage of Participants With Disease Progression or Death in EGFR Positive and Negative Population (Data Cut Off 07 September 2010)

FAS population; Only Participants with confirmed status of EGFR were included in the analysis; number of participants who were EGFR positive or negative

PFS in EGFR Positive and Negative Population (Data Cutoff 07 September 2010)

EGFR Positive (n=23,18)

EGFR Negative (n=4,5)

Participants received either pemetrexed500 mg/m\^2 every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable t oxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.

FAS population; n=number of EGFR positive or negative participants who remained at risk

Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months in EGFR Positive and Negative Population

Participants received a single oral dose of erlotinib 150 mg/day as a tablet until disease progression, unacceptable toxicity or death.

Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator Using RECIST

FAS population; Only participants with both a baseline FACT-L assessment and a subsequent FACT-L assessment were included in the analysis.

Percentage of Participants With Deterioration in Quality of Life Determined Using Functional Assessment of Cancer Therapy - Lung (FACT-L)

Time to Deterioration in Quality of Life Using FACT-L

Probable Percentage of Participants Remaining Without Deterioration in Quality of Life at 6 Months as Assessed by FACT-L

Percentage of Participants With Symptomatic Progression Using FACT-L

Time to Symptomatic Progression Using FACT-L

Probable Percentage of Participants With Symptomatic Progression at 6 Months as Assessed by FACT-L

Percentage of Participants With Deterioration in the Trial Outcome Index (TOI)

Time to Deterioration in the TOI

Probable Percentage of Participants With Deterioration in the TOI at 6 Months as Assessed by FACT-L

Participants received either pemetrexed 500 milligrams per square meter (mg/m\^2) every 21 days until disease progression, unacceptable toxicity or death or docetaxel 75 mg/m\^2 every 3 weeks until disease progression, unacceptable toxicity or death. Choice of comparator was left to the discretion of the investigator in countries where both treatments are registered to use and are commercially available for second line use (otherwise, docetaxel was administered), assigning the participant to either comparator depending upon the medical needs of the participant. Participants were required to receive concomitant treatment therapy as indicated in the product label.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Tarceva (Erlotinib) and Standard of Care Chemotherapy in Patients With Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer (NSCLC)	NCT00556322	Non-Small Cell ...	Alimta or Taxot... erlotinib [Tarc...	18 Years -	Hoffmann-La Roche
A Study of Tarceva (Erlotinib) and Standard of Care Chemotherapy in Patients With Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer (NSCLC)	NCT00556322	Non-Small Cell ...	Alimta or Taxot... erlotinib [Tarc...	18 Years -	Hoffmann-La Roche

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