Non-Small Cell Lung Cancer
Conditions
Brief summary
This 2 arm study will evaluate the management of Tarceva-induced skin rash in patients with non-small cell lung cancer who have failed first-line chemotherapy for advanced disease. Eligible patients will be randomized to receive a)doxycycline 100mg po daily or b)no preventative treatment; all patients will receive Tarceva 150mg/kg po daily. The anticipated time on study treatment is until disease progression or intolerable toxicity, and the target sample size is 100-500 individuals.
Interventions
DRUGDoxycline
100mg po daily
DRUGerlotinib [Tarceva]
150mg po daily
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* adult patients, 18-75 years of age; * confirmed non-small cell lung cancer; * failure after first line chemotherapy for advanced disease, and scheduled for second line therapy with Tarceva.
Exclusion criteria
* rash of any etiology at study entry; * history of significant heart disease; * any other malignancies (other than adequately treated squamous cell skin cancer, or in situ cancer of the cervix); * history of allergic reactions to tetracyclines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade During the First 4 Months of Treatment | Days 0, 14, 28 and Months 2, 3, and 4 | Description of skin rash (folliculitis, including erythema, papulo-pustules, nodule, and crust) was according to Common Terminology Criteria for Adverse Events (CTCAE) version 3 scale. Medical pictures of the face (front and sides views) systematically, and of any region presenting with skin lesions were obtained. The pictures were reviewed by a centralized committee of evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Days 0, 14, 28 and Months 2, 3, and 4 | A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust. |
| Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity | Days 0, 14, 28 and Months 2, 3, and 4 | Intensity of skin rashes was classified according to CTCAE grading. Grade 1 equals (=) Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering less than (\<)50 percent (%) of body surface area (BSA); Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation. |
| Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade After the First 4 Months of Treatment | Months 7, 10, and 12 | — |
| Number of Skin Rash (Folliculitis) Events After the First 4 Months of Treatment | Months 7, 10, and 12 | A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules. |
| Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Months 7, 10, and 12 | A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust. |
| Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity | Months 7, 10, and 12 | Intensity of skin rashes was classified according to CTCAE grading. Grade 1=Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering \<50% of BSA; Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation. |
| Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Number of Participants With an Event | Days 0, 14, 28 and Months 2, 3, and 4 | Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis. |
| Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Time to Event | Days 0, 14, 28 and Months 2, 3, and 4 | Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis. |
| Percentage of Participants Estimated to be Event Free at 4 Months | Days 0, 14, 28 and Months 2, 3, and 4 | Percentage of participants estimated to be without skin rash (folliculitis) at 4 months. |
| Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Number of Participants With an Event | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis. |
| Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Time to Event | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis. |
| Percentage of Participants Estimated to be Event Free at 12 Months | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | Percentage of participants estimated to be without skin rash (folliculitis) at 12 months. |
| Duration of Skin Rash (Folliculitis) During the First 4 Months of Treatment | Days 0, 14, 28 and Months 2, 3, and 4 | If the cutaneous rash was ongoing at the last visit or Month 4, the duration of cutaneous rash was calculated between start of folliculitis and Visit Month 4 or premature withdrawal visit or death. |
| Duration of Skin Rash (Folliculitis) During the Whole Treatment Period | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | If the end of cutaneous rash was missing, the duration of cutaneous rash was calculated between start of folliculitis and last evaluation date. |
| Percentage of Participants With Other Skin Lesions of Any Grade During the First 4 Months of Treatment | Days 0, 14, 28 and Months 2, 3, and 4 | Other skin lesions included presence or absence of xerosis and paronychia. |
| Number of Skin Rash (Folliculitis) Events During the First 4 Months of Treatment | Days 0, 14, 28 and Months 2, 3, and 4 | A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules. |
| Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Days 0, 14, 28 and Months 2, 3, and 4 | Other skin lesions included xerosis and paronychia. Intensity was classified according to CTCAE grading. Grade 1=Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering \<50% of BSA; Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation; Grade 4=Generalized exfoliative, ulcerative, or bullous dermatitis. If a participant had several skin lesions, the maximal intensity was taken into account. |
| Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | Erlotinib dose adjustment was done in case of toxicity occurrence. Keratitis, diarrhea, interstitial lung disease, and other toxic occurrences determined erlotinib dose reduction. If erlotinib was previously discontinued for skin rash or diarrhea of Grade 2 and if these symptoms of Grade 2 recurred OR if the symptoms were intolerable for the participants, erlotinib was discontinued until recovery/Grade 1 then the dose was reduced of one level of 50 mg. |
| Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | Occurrence of folliculitis-type skin rash of Grade greater than or equal to (≥)2 led to dose modification. Continuation of treatment with doxycycline after occurrence of folliculitis-type skin rash of Grade ≥2 was upon the investigator's opinion. |
| Percentage of Participants With Global Disease Control by Visit | Months 2, 4, 7, 10, and 12 | Disease control was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for evaluation and was defined as participants with either complete response (CR), partial response (PR), or stable disease (SD). |
| Percentage of Participants by Best Global Response Under Treatment | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | Response was determined according to the RECIST criteria for evaluation and was defined as participants with either CR, PR, SD, or progression. No CR was reported. |
| Progression-Free Survival (PFS) - Percentage of Participants With an Event | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | PFS was defined by the time between first intake of treatment with erlotinib and disease progression or death for any cause; estimated using Kaplan-Meier method. |
| Progression-Free Survival (PFS) - Time to Event | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | PFS was defined by the time between first intake of treatment with erlotinib and disease progression or death for any cause; estimated using Kaplan-Meier method. |
| Percentage of Participants Estimated to be Progression Free at 4 and 12 Months | Months 4 and 12 | — |
| Overall Survival (OS) - Percentage of Participants With an Event | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method. |
| Overall Survival (OS) - Time to Event | Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 | OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method. |
| Percentage of Participants Estimated to be Alive at 4 and 12 Months | Months 4 and 12 | — |
| Dermatology Life Quality Index (DLQI) Global Score | Baseline, Days 14 and 28 and Months 2, 3, and 4 | Quality of life was assessed by participant's responses to a DLQI questionnaire. The DLQI is a 10-item questionnaire assessing quality of life; questions were assessed on a 4-point scale (0=not at all; 1=a little; 2=a lot; and 3=very much). The DLQI was calculated by summing the score of each question resulting in a maximum of 30 (extremely large effect on participant's life) and a minimum of 0 (no effect at all on participant's life). The higher the score, the more quality of life is impaired. Analysis was performed by visit well as at the last available value after baseline (Endpoint); change from baseline to endpoint was also determined. |
| Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Baseline, Days 14 and 28 and Months 2, 3, and 4 | Quality of life was assessed by participant's responses to a DLQI questionnaire. The DLQI is a 10-item questionnaire assessing quality of life; questions were assessed on a 4-point scale (0=not at all; 1=a little; 2=a lot; and 3=very much). The DLQI was calculated by summing the score of each question resulting in a maximum of 30 (extremely large effect on participant's life) and a minimum of 0 (no effect at all on participant's life). The higher the score, the more quality of life is impaired. The DLQI global score was classified into 5 levels: 0-1 (no effect at all), 2-5 (small effect), 6-10 (moderate effect), 11-20 (very large effect) and 21-30 (extremely large effect). |
| Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Baseline, Days 14 and 28, and Months 2, 3, and 4 | Quality of life was assessed by participant's responses to a VAS questionnaire - (evaluation of satisfaction with skin status). VAS was measured on a 100 millimeter (mm) scale where 0 = not at all satisfied and 100 = very satisfied. Participants were asked to mark the line corresponding to their satisfaction at each visit and the distance from the left edge was measured. A negative change from baseline indicates improvement. Analysis was performed by visit well as at the last available value after baseline (Endpoint). |
| Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type | Days 0, 14, 28 and Months 2, 3, and 4 | Other skin lesions included xerosis and paronychia. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib + Doxycycline Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline. | 73 |
| Erlotinib Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity. | 74 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 8 |
| Overall Study | Death | 7 | 10 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Progression | 52 | 42 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Erlotinib + Doxycycline | Erlotinib | Total |
|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 10.6 | 64.2 years STANDARD_DEVIATION 11.1 | 63.8 years STANDARD_DEVIATION 10.8 |
| Sex: Female, Male Female | 25 Participants | 24 Participants | 49 Participants |
| Sex: Female, Male Male | 48 Participants | 50 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 71 / 73 | 69 / 74 |
| serious Total, serious adverse events | 18 / 73 | 24 / 74 |
Outcome results
Primary
Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade During the First 4 Months of Treatment
Description of skin rash (folliculitis, including erythema, papulo-pustules, nodule, and crust) was according to Common Terminology Criteria for Adverse Events (CTCAE) version 3 scale. Medical pictures of the face (front and sides views) systematically, and of any region presenting with skin lesions were obtained. The pictures were reviewed by a centralized committee of evaluation.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population; data for 1 participant in the erlotinib treatment group were missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade During the First 4 Months of Treatment | 71.2 percentage of participants |
| Erlotinib | Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade During the First 4 Months of Treatment | 80.8 percentage of participants |
p-value: 0.175Chi-squared
Secondary
Dermatology Life Quality Index (DLQI) Global Score
Quality of life was assessed by participant's responses to a DLQI questionnaire. The DLQI is a 10-item questionnaire assessing quality of life; questions were assessed on a 4-point scale (0=not at all; 1=a little; 2=a lot; and 3=very much). The DLQI was calculated by summing the score of each question resulting in a maximum of 30 (extremely large effect on participant's life) and a minimum of 0 (no effect at all on participant's life). The higher the score, the more quality of life is impaired. Analysis was performed by visit well as at the last available value after baseline (Endpoint); change from baseline to endpoint was also determined.
Time frame: Baseline, Days 14 and 28 and Months 2, 3, and 4
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erlotinib + Doxycycline | Dermatology Life Quality Index (DLQI) Global Score | Baseline (n=67,69) | 0.2 units on a scale | Standard Deviation 0.5 |
| Erlotinib + Doxycycline | Dermatology Life Quality Index (DLQI) Global Score | Day 14 (n=63,62) | 1.7 units on a scale | Standard Deviation 3.2 |
| Erlotinib + Doxycycline | Dermatology Life Quality Index (DLQI) Global Score | Day 28 (n=60,56) | 1.7 units on a scale | Standard Deviation 2.5 |
| Erlotinib + Doxycycline | Dermatology Life Quality Index (DLQI) Global Score | Month 2 (n=35,37) | 2.3 units on a scale | Standard Deviation 4.1 |
| Erlotinib + Doxycycline | Dermatology Life Quality Index (DLQI) Global Score | Month 3 (n=29,27) | 1.7 units on a scale | Standard Deviation 2.7 |
| Erlotinib + Doxycycline | Dermatology Life Quality Index (DLQI) Global Score | Month 4 (n=19,24) | 1.6 units on a scale | Standard Deviation 3 |
| Erlotinib + Doxycycline | Dermatology Life Quality Index (DLQI) Global Score | Endpoint (n=65,63) | 2.0 units on a scale | Standard Deviation 3.3 |
| Erlotinib + Doxycycline | Dermatology Life Quality Index (DLQI) Global Score | Change at Endpoint (n=35,37) | 1.9 units on a scale | Standard Deviation 3.3 |
| Erlotinib | Dermatology Life Quality Index (DLQI) Global Score | Change at Endpoint (n=35,37) | 3.2 units on a scale | Standard Deviation 4.8 |
| Erlotinib | Dermatology Life Quality Index (DLQI) Global Score | Baseline (n=67,69) | 0.2 units on a scale | Standard Deviation 0.6 |
| Erlotinib | Dermatology Life Quality Index (DLQI) Global Score | Month 3 (n=29,27) | 3.2 units on a scale | Standard Deviation 3.7 |
| Erlotinib | Dermatology Life Quality Index (DLQI) Global Score | Day 14 (n=63,62) | 3.7 units on a scale | Standard Deviation 4.3 |
| Erlotinib | Dermatology Life Quality Index (DLQI) Global Score | Endpoint (n=65,63) | 3.4 units on a scale | Standard Deviation 4.8 |
| Erlotinib | Dermatology Life Quality Index (DLQI) Global Score | Day 28 (n=60,56) | 3.4 units on a scale | Standard Deviation 4 |
| Erlotinib | Dermatology Life Quality Index (DLQI) Global Score | Month 4 (n=19,24) | 2.6 units on a scale | Standard Deviation 3.5 |
| Erlotinib | Dermatology Life Quality Index (DLQI) Global Score | Month 2 (n=35,37) | 4.3 units on a scale | Standard Deviation 5.3 |
Secondary
Duration of Skin Rash (Folliculitis) During the First 4 Months of Treatment
If the cutaneous rash was ongoing at the last visit or Month 4, the duration of cutaneous rash was calculated between start of folliculitis and Visit Month 4 or premature withdrawal visit or death.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT Population; only participants with an event (folliculitis) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erlotinib + Doxycycline | Duration of Skin Rash (Folliculitis) During the First 4 Months of Treatment | 59.6 days | Standard Deviation 35.9 |
| Erlotinib | Duration of Skin Rash (Folliculitis) During the First 4 Months of Treatment | 60.6 days | Standard Deviation 33.5 |
Secondary
Duration of Skin Rash (Folliculitis) During the Whole Treatment Period
If the end of cutaneous rash was missing, the duration of cutaneous rash was calculated between start of folliculitis and last evaluation date.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT Population; only participants with an event (folliculitis) were included in the analysis.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Erlotinib + Doxycycline | Duration of Skin Rash (Folliculitis) During the Whole Treatment Period | 86.7 days | Standard Deviation 81.1 |
| Erlotinib | Duration of Skin Rash (Folliculitis) During the Whole Treatment Period | 99.3 days | Standard Deviation 90.5 |
Secondary
Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity
Intensity of skin rashes was classified according to CTCAE grading. Grade 1=Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering \<50% of BSA; Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation.
Time frame: Months 7, 10, and 12
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity | Initial intensity: Grade 1 | 2 participants |
| Erlotinib + Doxycycline | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity | Maximal intensity: Grade 1 | 2 participants |
| Erlotinib | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity | Initial intensity: Grade 1 | 1 participants |
| Erlotinib | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity | Maximal intensity: Grade 1 | 1 participants |
Secondary
Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type
A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust.
Time frame: Months 7, 10, and 12
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Erythema | 1 participants |
| Erlotinib + Doxycycline | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Papulo-pustule | 1 participants |
| Erlotinib + Doxycycline | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Nodule | 0 participants |
| Erlotinib + Doxycycline | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Crust | 0 participants |
| Erlotinib | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Crust | 0 participants |
| Erlotinib | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Erythema | 1 participants |
| Erlotinib | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Nodule | 0 participants |
| Erlotinib | Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type | Papulo-pustule | 1 participants |
Secondary
Number of Skin Rash (Folliculitis) Events After the First 4 Months of Treatment
A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules.
Time frame: Months 7, 10, and 12
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Number of Skin Rash (Folliculitis) Events After the First 4 Months of Treatment | 2 rash events |
| Erlotinib | Number of Skin Rash (Folliculitis) Events After the First 4 Months of Treatment | 1 rash events |
Secondary
Number of Skin Rash (Folliculitis) Events During the First 4 Months of Treatment
A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Number of Skin Rash (Folliculitis) Events During the First 4 Months of Treatment | 57 rash events |
| Erlotinib | Number of Skin Rash (Folliculitis) Events During the First 4 Months of Treatment | 62 rash events |
Secondary
Overall Survival (OS) - Percentage of Participants With an Event
OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Overall Survival (OS) - Percentage of Participants With an Event | 71.2 percentage of participants |
| Erlotinib | Overall Survival (OS) - Percentage of Participants With an Event | 67.6 percentage of participants |
Secondary
Overall Survival (OS) - Time to Event
OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib + Doxycycline | Overall Survival (OS) - Time to Event | 227.0 days |
| Erlotinib | Overall Survival (OS) - Time to Event | 251.0 days |
Secondary
Percentage of Participants by Best Global Response Under Treatment
Response was determined according to the RECIST criteria for evaluation and was defined as participants with either CR, PR, SD, or progression. No CR was reported.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants by Best Global Response Under Treatment | PR | 15.5 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants by Best Global Response Under Treatment | SD | 36.2 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants by Best Global Response Under Treatment | Progression | 48.3 percentage of participants |
| Erlotinib | Percentage of Participants by Best Global Response Under Treatment | PR | 10.3 percentage of participants |
| Erlotinib | Percentage of Participants by Best Global Response Under Treatment | SD | 48.3 percentage of participants |
| Erlotinib | Percentage of Participants by Best Global Response Under Treatment | Progression | 41.4 percentage of participants |
Secondary
Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life
Quality of life was assessed by participant's responses to a DLQI questionnaire. The DLQI is a 10-item questionnaire assessing quality of life; questions were assessed on a 4-point scale (0=not at all; 1=a little; 2=a lot; and 3=very much). The DLQI was calculated by summing the score of each question resulting in a maximum of 30 (extremely large effect on participant's life) and a minimum of 0 (no effect at all on participant's life). The higher the score, the more quality of life is impaired. The DLQI global score was classified into 5 levels: 0-1 (no effect at all), 2-5 (small effect), 6-10 (moderate effect), 11-20 (very large effect) and 21-30 (extremely large effect).
Time frame: Baseline, Days 14 and 28 and Months 2, 3, and 4
Population: ITT Population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, no effect (n=35,37) | 65.7 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, no effect (n=60,56) | 66.7 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, small effect (n=60,56) | 25.0 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, moderate effect (n=60,56) | 8.3 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, very large effect (n=60,56) | 0.0 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, extremely large effect (n=60,56) | 0.0 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, extremely large effect (n=63,62) | 1.6 percentage of participants | 3 |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, small effect (n=35,37) | 22.9 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, moderate effect (n=35,37) | 5.7 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, very large effect (n=35,37) | 5.7 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, extremely large effect (n=35,37) | 0.0 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 3, no effect (n=29,27) | 69.0 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 3, small effect (n=29,27) | 27.6 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 3, moderate effect (n=29,27) | 0.0 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 3, very large effect (n=29,27) | 3.4 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 4, no effect (n=19,24) | 78.9 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 4, small effect (n=19,24) | 15.8 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 4, very large effect (n=19,24) | 5.3 percentage of participants | — |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Baseline, no effect (n=67,69) | 98.5 percentage of participants | 0.5 |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Baseline, small effect (n=67,69) | 1.5 percentage of participants | 3.2 |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, no effect (n=63,62) | 69.8 percentage of participants | 2.5 |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, small effect (n=63,62) | 27.0 percentage of participants | 3.3 |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, moderate effect (n=63,62) | 0.0 percentage of participants | 4.1 |
| Erlotinib + Doxycycline | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, very large effect (n=63,62) | 1.6 percentage of participants | 2.7 |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, moderate effect (n=63,62) | 21.0 percentage of participants | 5.3 |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, extremely large effect (n=63,62) | 0.0 percentage of participants | 3.5 |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 3, small effect (n=29,27) | 44.4 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, no effect (n=60,56) | 41.1 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Baseline, no effect (n=67,69) | 97.1 percentage of participants | 0.6 |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, small effect (n=60,56) | 35.7 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 3, moderate effect (n=29,27) | 11.1 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, moderate effect (n=60,56) | 19.6 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, small effect (n=63,62) | 30.6 percentage of participants | 4.8 |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, very large effect (n=60,56) | 1.8 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 3, very large effect (n=29,27) | 7.4 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 28, extremely large effect (n=60,56) | 1.8 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Baseline, small effect (n=67,69) | 2.9 percentage of participants | 4.3 |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, no effect (n=35,37) | 40.5 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 4, no effect (n=19,24) | 50.0 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, small effect (n=35,37) | 27.0 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, very large effect (n=63,62) | 6.5 percentage of participants | 3.7 |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, moderate effect (n=35,37) | 21.6 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 4, small effect (n=19,24) | 41.7 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, very large effect (n=35,37) | 8.1 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Day 14, no effect (n=63,62) | 41.9 percentage of participants | 4 |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 2, extremely large effect (n=35,37) | 2.7 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 4, very large effect (n=19,24) | 8.3 percentage of participants | — |
| Erlotinib | Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life | Month 3, no effect (n=29,27) | 37.0 percentage of participants | — |
Secondary
Percentage of Participants Estimated to be Alive at 4 and 12 Months
Time frame: Months 4 and 12
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants Estimated to be Alive at 4 and 12 Months | 4 Months | 68.5 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants Estimated to be Alive at 4 and 12 Months | 12 Months | 27.1 percentage of participants |
| Erlotinib | Percentage of Participants Estimated to be Alive at 4 and 12 Months | 4 Months | 69.7 percentage of participants |
| Erlotinib | Percentage of Participants Estimated to be Alive at 4 and 12 Months | 12 Months | 33.5 percentage of participants |
Secondary
Percentage of Participants Estimated to be Event Free at 12 Months
Percentage of participants estimated to be without skin rash (folliculitis) at 12 months.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants Estimated to be Event Free at 12 Months | 19.8 percentage of participants |
| Erlotinib | Percentage of Participants Estimated to be Event Free at 12 Months | 11.2 percentage of participants |
Secondary
Percentage of Participants Estimated to be Event Free at 4 Months
Percentage of participants estimated to be without skin rash (folliculitis) at 4 months.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants Estimated to be Event Free at 4 Months | 24.7 percentage of participants |
| Erlotinib | Percentage of Participants Estimated to be Event Free at 4 Months | 11.2 percentage of participants |
Secondary
Percentage of Participants Estimated to be Progression Free at 4 and 12 Months
Time frame: Months 4 and 12
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants Estimated to be Progression Free at 4 and 12 Months | 4 Months | 30.1 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants Estimated to be Progression Free at 4 and 12 Months | 12 Months | 6.3 percentage of participants |
| Erlotinib | Percentage of Participants Estimated to be Progression Free at 4 and 12 Months | 4 Months | 31.0 percentage of participants |
| Erlotinib | Percentage of Participants Estimated to be Progression Free at 4 and 12 Months | 12 Months | 10.8 percentage of participants |
Secondary
Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade After the First 4 Months of Treatment
Time frame: Months 7, 10, and 12
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade After the First 4 Months of Treatment | 2.7 percentage of participants |
| Erlotinib | Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade After the First 4 Months of Treatment | 1.4 percentage of participants |
Secondary
Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction
Occurrence of folliculitis-type skin rash of Grade greater than or equal to (≥)2 led to dose modification. Continuation of treatment with doxycycline after occurrence of folliculitis-type skin rash of Grade ≥2 was upon the investigator's opinion.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT population; only participants that discontinued or interrupted doxycycline were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction | Adverse event | 50.0 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction | Other | 50.0 percentage of participants |
Secondary
Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction
Erlotinib dose adjustment was done in case of toxicity occurrence. Keratitis, diarrhea, interstitial lung disease, and other toxic occurrences determined erlotinib dose reduction. If erlotinib was previously discontinued for skin rash or diarrhea of Grade 2 and if these symptoms of Grade 2 recurred OR if the symptoms were intolerable for the participants, erlotinib was discontinued until recovery/Grade 1 then the dose was reduced of one level of 50 mg.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT population; only participants that discontinued or interrupted erlotinib were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction | Adverse event | 80.0 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction | Investigator's decision | 0 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction | Other | 20.0 percentage of participants |
| Erlotinib | Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction | Adverse event | 85.7 percentage of participants |
| Erlotinib | Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction | Investigator's decision | 2.4 percentage of participants |
| Erlotinib | Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction | Other | 11.9 percentage of participants |
Secondary
Percentage of Participants With Global Disease Control by Visit
Disease control was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for evaluation and was defined as participants with either complete response (CR), partial response (PR), or stable disease (SD).
Time frame: Months 2, 4, 7, 10, and 12
Population: ITT population; number (n) = number of participants analyzed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With Global Disease Control by Visit | Month 4 (n=19,25) | 89.5 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Global Disease Control by Visit | Month 10 (n=7,12) | 100.0 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Global Disease Control by Visit | Month 7 (n=11,17) | 72.7 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Global Disease Control by Visit | Month 12 (n=7,10) | 71.4 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Global Disease Control by Visit | Month 2 (n=34,33) | 88.2 percentage of participants |
| Erlotinib | Percentage of Participants With Global Disease Control by Visit | Month 12 (n=7,10) | 40.0 percentage of participants |
| Erlotinib | Percentage of Participants With Global Disease Control by Visit | Month 2 (n=34,33) | 93.9 percentage of participants |
| Erlotinib | Percentage of Participants With Global Disease Control by Visit | Month 4 (n=19,25) | 80.0 percentage of participants |
| Erlotinib | Percentage of Participants With Global Disease Control by Visit | Month 7 (n=11,17) | 76.5 percentage of participants |
| Erlotinib | Percentage of Participants With Global Disease Control by Visit | Month 10 (n=7,12) | 66.7 percentage of participants |
Secondary
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity
Other skin lesions included xerosis and paronychia. Intensity was classified according to CTCAE grading. Grade 1=Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering \<50% of BSA; Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation; Grade 4=Generalized exfoliative, ulcerative, or bullous dermatitis. If a participant had several skin lesions, the maximal intensity was taken into account.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population; only participants with an adverse event classified as other skin lesion during the first 4 months were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Grade 1 | 69.0 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Grade 2 | 24.1 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Grade 3 | 6.9 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Grade 4 | 0 percentage of participants |
| Erlotinib | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Grade 4 | 3.2 percentage of participants |
| Erlotinib | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Grade 1 | 29.0 percentage of participants |
| Erlotinib | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Grade 3 | 16.1 percentage of participants |
| Erlotinib | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity | Grade 2 | 51.6 percentage of participants |
Comparison: Erlotinib + doxycycline vs Erlotinib: Grade 3p-value: 0.003Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type
Other skin lesions included xerosis and paronychia.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type | Xerosis | 37.0 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type | Paronychia | 6.8 percentage of participants |
| Erlotinib | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type | Xerosis | 41.1 percentage of participants |
| Erlotinib | Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type | Paronychia | 8.2 percentage of participants |
Secondary
Percentage of Participants With Other Skin Lesions of Any Grade During the First 4 Months of Treatment
Other skin lesions included presence or absence of xerosis and paronychia.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With Other Skin Lesions of Any Grade During the First 4 Months of Treatment | 39.7 percentage of participants |
| Erlotinib | Percentage of Participants With Other Skin Lesions of Any Grade During the First 4 Months of Treatment | 42.5 percentage of participants |
Secondary
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity
Intensity of skin rashes was classified according to CTCAE grading. Grade 1 equals (=) Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering less than (\<)50 percent (%) of body surface area (BSA); Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population; only participants with an adverse event of skin rash (folliculitis) during the first 4 months were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity | Grade 1 | 61.5 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity | Grade 2 | 34.6 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity | Grade 3 | 3.8 percentage of participants |
| Erlotinib | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity | Grade 1 | 18.6 percentage of participants |
| Erlotinib | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity | Grade 2 | 62.7 percentage of participants |
| Erlotinib | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity | Grade 3 | 18.6 percentage of participants |
Comparison: Erlotinib + doxycycline vs Erlotinib: Grade 3 intensity skin rash (folliculitis)p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type
A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Doxycycline | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Erythema | 55.8 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Papulo-pustule | 65.4 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Nodule | 1.9 percentage of participants |
| Erlotinib + Doxycycline | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Crust | 9.6 percentage of participants |
| Erlotinib | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Crust | 25.9 percentage of participants |
| Erlotinib | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Erythema | 70.7 percentage of participants |
| Erlotinib | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Nodule | 0 percentage of participants |
| Erlotinib | Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type | Papulo-pustule | 72.4 percentage of participants |
Secondary
Progression-Free Survival (PFS) - Percentage of Participants With an Event
PFS was defined by the time between first intake of treatment with erlotinib and disease progression or death for any cause; estimated using Kaplan-Meier method.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Progression-Free Survival (PFS) - Percentage of Participants With an Event | 91.8 percentage of participants |
| Erlotinib | Progression-Free Survival (PFS) - Percentage of Participants With an Event | 87.8 percentage of participants |
Secondary
Progression-Free Survival (PFS) - Time to Event
PFS was defined by the time between first intake of treatment with erlotinib and disease progression or death for any cause; estimated using Kaplan-Meier method.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib + Doxycycline | Progression-Free Survival (PFS) - Time to Event | 63.0 days |
| Erlotinib | Progression-Free Survival (PFS) - Time to Event | 70.0 days |
Secondary
Quality of Life Score as Assessed by Visual Analog Scale (VAS)
Quality of life was assessed by participant's responses to a VAS questionnaire - (evaluation of satisfaction with skin status). VAS was measured on a 100 millimeter (mm) scale where 0 = not at all satisfied and 100 = very satisfied. Participants were asked to mark the line corresponding to their satisfaction at each visit and the distance from the left edge was measured. A negative change from baseline indicates improvement. Analysis was performed by visit well as at the last available value after baseline (Endpoint).
Time frame: Baseline, Days 14 and 28, and Months 2, 3, and 4
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Baseline (n=64,68) | 81.4 mm | Standard Deviation 23.7 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Day 14 (n=62,63) | 68.8 mm | Standard Deviation 26.6 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Change at Day 14 (n=59,61) | -16.2 mm | Standard Deviation 28.5 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Day 28 (n=59,56) | 66.5 mm | Standard Deviation 27.2 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Change at Day 28 (n=55,54) | -15.5 mm | Standard Deviation 28.8 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Month 2 (n=36,36) | 68.9 mm | Standard Deviation 22.8 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Month 3 (n=28,27) | 63.5 mm | Standard Deviation 21.4 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Month 4 (n=18,24) | 71.8 mm | Standard Deviation 20.9 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Endpoint (n=65,64) | 64.0 mm | Standard Deviation 26.6 |
| Erlotinib + Doxycycline | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Change at Endpoint (n=60,62) | -18.1 mm | Standard Deviation 27.7 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Month 4 (n=18,24) | 59.9 mm | Standard Deviation 29.7 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Baseline (n=64,68) | 87.8 mm | Standard Deviation 19.6 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Month 2 (n=36,36) | 52.6 mm | Standard Deviation 27.4 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Day 14 (n=62,63) | 51.0 mm | Standard Deviation 34.5 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Change at Endpoint (n=60,62) | -30.4 mm | Standard Deviation 31.4 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Change at Day 14 (n=59,61) | -39.2 mm | Standard Deviation 37.8 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Month 3 (n=28,27) | 56.1 mm | Standard Deviation 31.7 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Day 28 (n=59,56) | 54.8 mm | Standard Deviation 27 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Endpoint (n=65,64) | 58.3 mm | Standard Deviation 30.8 |
| Erlotinib | Quality of Life Score as Assessed by Visual Analog Scale (VAS) | Change at Day 28 (n=55,54) | -35.1 mm | Standard Deviation 27.8 |
Secondary
Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Number of Participants With an Event
Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Number of Participants With an Event | 52 participants |
| Erlotinib | Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Number of Participants With an Event | 59 participants |
Secondary
Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Time to Event
Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.
Time frame: Days 0, 14, 28 and Months 2, 3, and 4
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib + Doxycycline | Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Time to Event | 14 days |
| Erlotinib | Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Time to Event | 13 days |
p-value: 0.14395% CI: [0.525, 1.109]Log Rank
Secondary
Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Number of Participants With an Event
Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Doxycycline | Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Number of Participants With an Event | 53 participants |
| Erlotinib | Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Number of Participants With an Event | 59 participants |
Secondary
Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Time to Event
Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.
Time frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib + Doxycycline | Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Time to Event | 14 days |
| Erlotinib | Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Time to Event | 13 days |
p-value: 0.15395% CI: [0.529, 1.116]Log Rank