Trial Outcomes & Findings for A Study of Tarceva (Erlotinib) to Compare Two Different Doses in in Currently Smoking Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (CURRENTS) (NCT NCT01183858)

Last Updated: 2015-08-19

Results Overview

PFS is defined as the time from randomization to the date of first occurrence of disease progression or death. For target lesions, Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

315 participants

Primary outcome timeframe

Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 Months)

Results posted on

2015-08-19

Participant Flow

315 participants were randomized. 313 participants were included in the Intent-to -treat (ITT) population. The ITT population excluded 2 randomized participants: 1 participant randomized in error and 1 participant with missing source data.

Participant milestones

Participant milestones
Measure	Erlotinib 150 mg Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg Erlotinib 300 mg single daily oral dose until disease progression.
Overall Study STARTED	154	159
Overall Study Safety Population	154	158
Overall Study COMPLETED	1	3
Overall Study NOT COMPLETED	153	156

Reasons for withdrawal

Reasons for withdrawal
Measure	Erlotinib 150 mg Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg Erlotinib 300 mg single daily oral dose until disease progression.
Overall Study Death not related to Progressive Disease	5	6
Overall Study Adverse Event	14	11
Overall Study Investigator's Decision	0	3
Overall Study Insufficient Therapeutic Response	2	0
Overall Study Refused Treatment	1	4
Overall Study Withdrew Consent	4	4
Overall Study Discontinued Smoking	3	1
Overall Study Protocol Violation	1	0
Overall Study Administrative/Other	6	6
Overall Study Progressive Disease	112	115
Overall Study Death related to Progressive Disease	4	5
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

A Study of Tarceva (Erlotinib) to Compare Two Different Doses in in Currently Smoking Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (CURRENTS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=159 Participants Erlotinib 300 mg single daily oral dose until disease progression.	Total n=313 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 9.25 • n=93 Participants	59.2 years STANDARD_DEVIATION 9.14 • n=4 Participants	59.4 years STANDARD_DEVIATION 9.18 • n=27 Participants
Sex: Female, Male Female	34 Participants n=93 Participants	35 Participants n=4 Participants	69 Participants n=27 Participants
Sex: Female, Male Male	120 Participants n=93 Participants	124 Participants n=4 Participants	244 Participants n=27 Participants

PRIMARY outcome

Timeframe: Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 Months)

Population: Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=159 Participants Erlotinib 300 mg single daily oral dose until disease progression.
Progression-Free Survival (PFS)	6.86 weeks Interval 6.29 to 12.0	7.00 weeks Interval 6.29 to 11.0

PRIMARY outcome

Timeframe: Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months)

Population: Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=159 Participants Erlotinib 300 mg single daily oral dose until disease progression.
Progression-Free Survival (PFS) at the End of Study	6.86 weeks Interval 6.29 to 12.0	7.00 weeks Interval 6.29 to 11.43

SECONDARY outcome

Timeframe: Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)

Population: Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

OS defined as the time from randomization to the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=159 Participants Erlotinib 300 mg single daily oral dose until disease progression.
Overall Survival (OS)	6.77 months Interval 5.65 to 8.77	6.83 months Interval 5.39 to 8.48

SECONDARY outcome

Timeframe: Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)

Population: Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant was defined as a responder if they sustained a complete response (CR) or partial response (PR) for at least 4 weeks during randomized treatment (confirmed response). Patients with no tumor assessment after the start of study treatment were to be considered as non-responders. The percentage of participants in each best response category is presented.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=159 Participants Erlotinib 300 mg single daily oral dose until disease progression.
Overall Response Rate (ORR) Not Evaluable	14.9 percentage of participants Interval 9.7 to 21.6	17.6 percentage of participants Interval 12.0 to 24.4
Overall Response Rate (ORR) Partial Response	7.1 percentage of participants Interval 3.6 to 12.4	2.5 percentage of participants Interval 0.7 to 6.3
Overall Response Rate (ORR) Complete Response	0.0 percentage of participants Interval 0.0 to 0.0	0.0 percentage of participants Interval 0.0 to 0.0
Overall Response Rate (ORR) Stable Disease	33.1 percentage of participants Interval 25.8 to 41.1	34.0 percentage of participants Interval 26.6 to 41.9
Overall Response Rate (ORR) Progressive Disease	44.8 percentage of participants Interval 36.8 to 53.0	45.9 percentage of participants Interval 38.0 to 54.0

SECONDARY outcome

Timeframe: Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)

Population: Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans. Disease control rates were measured according to RECIST version 1.1 criteria. A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) for at least 4 weeks during randomized treatment (confirmed response), or Stable Disease (SD) for at least 6 weeks. Patients with no tumor assessment after the start of study treatment were considered as having uncontrolled disease. The percentage of participants with Disease Control is presented.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=159 Participants Erlotinib 300 mg single daily oral dose until disease progression.
Disease Control Rate (DCR)	40.3 percentage of participants Interval 32.4 to 48.5	36.5 percentage of participants Interval 29.0 to 44.5

SECONDARY outcome

Timeframe: Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)

Population: Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Time to progression (TTP) in weeks was defined as the time from randomization to the date of disease progression. Participants without event were censored at the date of the last tumor assessment when the patient was known to be progression free.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=159 Participants Erlotinib 300 mg single daily oral dose until disease progression.
Time to Progression (TTP)	9.86 weeks Interval 6.43 to 12.14	9.14 weeks Interval 6.43 to 12.0

SECONDARY outcome

Timeframe: Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months)

Population: Safety population included all randomized participants who received at least one dose of study drug.

An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Adverse Events in the following categories are presented: Adverse Events, Serious Adverse Events, AEs leading to withdrawal from treatment and AEs leading to death.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=158 Participants Erlotinib 300 mg single daily oral dose until disease progression.
Number of Participants With Adverse Events (AEs) at the End of the Study Adverse Events (AEs)	130 participants	141 participants
Number of Participants With Adverse Events (AEs) at the End of the Study Serious Adverse Events	29 participants	35 participants
Number of Participants With Adverse Events (AEs) at the End of the Study AEs leading to withdrawal	18 participants	15 participants
Number of Participants With Adverse Events (AEs) at the End of the Study AEs leading to death	12 participants	13 participants

SECONDARY outcome

Timeframe: Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months)

Population: Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.

OS defined as the time from randomization to the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Erlotinib 150 mg n=154 Participants Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=159 Participants Erlotinib 300 mg single daily oral dose until disease progression.
Overall Survival (OS) at the End of Study	7.00 months Interval 5.65 to 8.84	6.90 months Interval 5.62 to 8.64

Adverse Events

Erlotinib 150 mg

Serious events: 29 serious events

Other events: 115 other events

Deaths: 0 deaths

Erlotinib 300 mg

Serious events: 35 serious events

Other events: 128 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

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

Measure	Erlotinib 150 mg n=154 participants at risk Erlotinib 150 mg single daily oral dose until disease progression.	Erlotinib 300 mg n=158 participants at risk Erlotinib 300 mg single daily oral dose until disease progression.
Skin and subcutaneous tissue disorders Rash	27.9% 43/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	47.5% 75/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	8.4% 13/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	10.8% 17/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	5.2% 8/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	10.1% 16/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis acneiform	7.1% 11/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	5.7% 9/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	18.8% 29/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	29.1% 46/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	13.0% 20/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	10.8% 17/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	8.4% 13/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	8.9% 14/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	5.8% 9/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	7.0% 11/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	1.9% 3/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	5.1% 8/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.65% 1/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	5.1% 8/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
General disorders Fatigue	13.6% 21/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	16.5% 26/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
General disorders Chest pain	4.5% 7/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	8.9% 14/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
General disorders Asthenia	5.8% 9/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	7.6% 12/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
General disorders Pain	5.2% 8/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	3.2% 5/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.9% 26/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	12.0% 19/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	14.9% 23/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	12.0% 19/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased appetite	16.9% 26/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	20.3% 32/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Investigations Weight decreased	4.5% 7/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	9.5% 15/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Anaemia	3.9% 6/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	5.1% 8/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 3/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	5.1% 8/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Nervous system disorders Headache	5.8% 9/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	1.3% 2/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	5.2% 8/154 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.	3.8% 6/158 • Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) Safety population: All participants who received at least 1 dose of study drug.