Trial Outcomes & Findings for A Study of Erlotinib [Tarceva] as Monotherapy or Intermittent Dosing With Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer. (TALISMAN) (NCT NCT01204697)

NCT ID: NCT01204697

Last Updated: 2015-11-16

Results Overview

According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, progressive Disease (PD) is defined as: for Target Lesions - At least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). (Note: the appearance of one or more new lesions is also considered progression). For Non-Target Lesions - Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

74 participants

Primary outcome timeframe

Month 6

Results posted on

2015-11-16

Participant Flow

Participant milestones

Participant milestones
Measure	Erlotinib Participants received erlotinib (Tarceva) at a dose of 150 milligram per day (mg/day) orally as monotherapy, up to progressive disease (PD), death, or unacceptable toxicity.	Docetaxel and Erlotinib Participants received docetaxel at a dose of 75 milligram per square meter (mg/m\^2) as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Overall Study STARTED	36	38
Overall Study Treated	36	37
Overall Study COMPLETED	5	2
Overall Study NOT COMPLETED	31	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Erlotinib Participants received erlotinib (Tarceva) at a dose of 150 milligram per day (mg/day) orally as monotherapy, up to progressive disease (PD), death, or unacceptable toxicity.	Docetaxel and Erlotinib Participants received docetaxel at a dose of 75 milligram per square meter (mg/m\^2) as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Overall Study Death	26	27
Overall Study Lost to Follow-up	3	4
Overall Study Withdrawal by Subject	2	4
Overall Study Randomized, but not treated	0	1

Baseline Characteristics

A Study of Erlotinib [Tarceva] as Monotherapy or Intermittent Dosing With Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer. (TALISMAN)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erlotinib n=36 Participants Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=37 Participants Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.	Total n=73 Participants Total of all reporting groups
Age, Continuous	68.4 years STANDARD_DEVIATION 8.3 • n=5 Participants	65.9 years STANDARD_DEVIATION 8.1 • n=7 Participants	67.2 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	36 Participants n=7 Participants	72 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 6

Population: FAS population

Outcome measures

Outcome measures
Measure	Erlotinib n=36 Participants Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=37 Participants Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Percentage of Participants Free From Disease Progression or Death at 6 Months	8.3 percentage of participants Interval 0.0 to 17.4	8.1 percentage of participants Interval 0.0 to 16.9

SECONDARY outcome

Timeframe: From randomization until progressive disease or death, assessed up to 18 months

Population: FAS population

Progression-free Survival (PFS) was defined as the interval (in days) between the date of randomization and the first documentation of progressive disease or death from any cause. Participants alive and progression-free were considered as censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without post-baseline tumor assessment, but known to be alive, were censored at the time of randomization. PFS (days) = (Date of Event - Date of Randomization) + 1. PFS was assessed using the Kaplan-Meier method. Detailed definition of PD is provided in Outcome Measure 1.

Outcome measures

Outcome measures
Measure	Erlotinib n=36 Participants Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=37 Participants Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Progression-free Survival (PFS)	2.33 months Interval 2.13 to 4.13	2.82 months Interval 2.3 to 3.97

SECONDARY outcome

Timeframe: From randomization until death, assessed up to 18 months

Population: FAS population

Overall survival (OS) was defined as the interval (in days) between the date of randomization and death from any cause. Participants alive at the time of the analysis were censored at the date they were last known to be alive. OS was assessed using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Erlotinib n=36 Participants Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=37 Participants Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Overall Survival (OS)	5.61 months Interval 3.54 to 8.69	8.95 months Interval 6.13 to 10.4

SECONDARY outcome

Timeframe: From randomization until progressive disease or death, assessed up to 18 months

Population: FAS population

Best overall response (complete response \[CR\]/partial response \[PR\]) was defined as the best response recorded from the start of the treatment until disease progression (PD). Best response in this trial was defined as the best response observed at any post-treatment visits. According to RECIST Version 1.1, CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than \[\<\] 10 mm). No new lesions. PR was defined as greater than or equal to \[\>=\] 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

Outcome measures

Outcome measures
Measure	Erlotinib n=36 Participants Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=37 Participants Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR)	2.8 percentage of participants Interval 0.0 to 8.15	8.1 percentage of participants Interval 0.0 to 16.9

SECONDARY outcome

Timeframe: From randomization until progressive disease or death, assessed up to 18 months

Population: FAS population

Disease control was defined as PR, CR, or SD. Participants who did not achieve a CR or PR or SD were counted as non-responders in the analysis of disease control. According to RECIST Version 1.1, SD was defined as not qualifying for CR, PR, and PD. Detailed definitions of CR and PR are provided in Outcome Measure 4.

Outcome measures

Outcome measures
Measure	Erlotinib n=36 Participants Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=37 Participants Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Percentage of Participants With Disease Control	41.7 percentage of participants Interval 25.6 to 57.8	37.8 percentage of participants Interval 22.2 to 53.5

SECONDARY outcome

Timeframe: From randomization until progressive disease or death, assessed up to 18 months

Population: FAS population. Here, number of participants analyzed signifies those participants who had a best overall response of CR or PR.

Duration of response (DoR) was defined as the interval (in days) from first documentation of a response (CR/PR depending on which occurred first) to the date of the first documentation of disease progression or death from any cause. Participants presenting a response were considered as censored at the date of the last assessment with a documentation of non-progression. DoR (days) = (Date of PD/death - Date of CR/PR) + 1. Assessments were performed according to RECIST Version 1.1. DoR was assessed using the Kaplan-Meier method. Detailed definitions of CR and PR are provided in Outcome Measure 4.

Outcome measures

Outcome measures
Measure	Erlotinib n=1 Participants Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=3 Participants Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Duration of Response (DoR)	NA months Median and corresponding 95% confidence interval were not estimable as the only participant evaluable was censored.	8.69 months Interval 1.87 to 10.8

Adverse Events

Erlotinib

Serious events: 15 serious events

Other events: 32 other events

Deaths: 0 deaths

Docetaxel and Erlotinib

Serious events: 10 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Erlotinib n=36 participants at risk Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=37 participants at risk Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/36 • Up to 18 months	10.8% 4/37 • Up to 18 months
Blood and lymphatic system disorders Neutropenia	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months
Cardiac disorders Cardiac tamponade	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Gastrointestinal disorders Abdominal pain	0.00% 0/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
Gastrointestinal disorders Gastrointestinal haemorrhage	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Gastrointestinal disorders Gastrointestinal ulcer haemorrhage	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
General disorders Chest pain	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
General disorders Device dislocation	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
General disorders General physical health deterioration	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
General disorders Mucosal inflammation	0.00% 0/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
General disorders Performance status decreased	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Immune system disorders Anaphylactic reaction	0.00% 0/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
Infections and infestations Pneumonia	0.00% 0/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
Infections and infestations Sepsis	0.00% 0/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
Infections and infestations Urinary tract infection	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Metabolism and nutrition disorders Cachexia	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Metabolism and nutrition disorders Dehydration	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Metabolism and nutrition disorders Diabetes mellitus inadequate control	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Musculoskeletal and connective tissue disorders Muscular weakness	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Renal and urinary disorders Renal failure acute	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.8% 1/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Cough	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 3/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Lung disorder	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.00% 0/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
General disorders Uncoded	0.00% 0/36 • Up to 18 months	2.7% 1/37 • Up to 18 months
Vascular disorders Angiopathy	2.8% 1/36 • Up to 18 months	0.00% 0/37 • Up to 18 months

Other adverse events

Other adverse events
Measure	Erlotinib n=36 participants at risk Participants received erlotinib at a dose of 150 mg/day orally as monotherapy, up to PD, death, or unacceptable toxicity.	Docetaxel and Erlotinib n=37 participants at risk Participants received docetaxel at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 3-week cycle, and erlotinib at a dose of 150 mg/day orally from Day 2 to Day 16 of each 3-week cycle for 4 cycles, administered in absence of PD, death, or unacceptable toxicity. Following the 4 cycles, erlotinib 150 mg/day was administered orally as monotherapy up to PD, death or unacceptable toxicity.
Blood and lymphatic system disorders Anaemia	11.1% 4/36 • Up to 18 months	8.1% 3/37 • Up to 18 months
Blood and lymphatic system disorders Leukopenia	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months
Blood and lymphatic system disorders Neutropenia	0.00% 0/36 • Up to 18 months	24.3% 9/37 • Up to 18 months
Cardiac disorders Tachycardia	0.00% 0/36 • Up to 18 months	8.1% 3/37 • Up to 18 months
Gastrointestinal disorders Abdominal pain	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Gastrointestinal disorders Abdominal pain upper	8.3% 3/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Gastrointestinal disorders Diarrhoea	25.0% 9/36 • Up to 18 months	37.8% 14/37 • Up to 18 months
Gastrointestinal disorders Dyspepsia	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months
Gastrointestinal disorders Dysphagia	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Gastrointestinal disorders Nausea	5.6% 2/36 • Up to 18 months	8.1% 3/37 • Up to 18 months
Gastrointestinal disorders Vomiting	0.00% 0/36 • Up to 18 months	13.5% 5/37 • Up to 18 months
General disorders Asthenia	22.2% 8/36 • Up to 18 months	27.0% 10/37 • Up to 18 months
General disorders Chest pain	13.9% 5/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
General disorders Mucosal inflammation	0.00% 0/36 • Up to 18 months	13.5% 5/37 • Up to 18 months
General disorders Pyrexia	11.1% 4/36 • Up to 18 months	16.2% 6/37 • Up to 18 months
Hepatobiliary disorders Hypertransaminasaemia	8.3% 3/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Immune system disorders Anaphylactic reaction	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months
Infections and infestations Folliculitis	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Metabolism and nutrition disorders Decreased appetite	5.6% 2/36 • Up to 18 months	8.1% 3/37 • Up to 18 months
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Musculoskeletal and connective tissue disorders Neck pain	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Nervous system disorders Coordination abnormal	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months
Nervous system disorders Dysgeusia	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Nervous system disorders Neuropathy peripheral	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Cough	11.1% 4/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 3/36 • Up to 18 months	18.9% 7/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Haemoptysis	8.3% 3/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months
Skin and subcutaneous tissue disorders Dry skin	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Skin and subcutaneous tissue disorders Erythema	8.3% 3/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Skin and subcutaneous tissue disorders Pruritus	5.6% 2/36 • Up to 18 months	0.00% 0/37 • Up to 18 months
Skin and subcutaneous tissue disorders Rash	44.4% 16/36 • Up to 18 months	32.4% 12/37 • Up to 18 months
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/36 • Up to 18 months	5.4% 2/37 • Up to 18 months

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER