Lung Cancer
Conditions
Keywords
Cancer, Non-small-cell lung cancer, Adenocarcinoma, EGFR gene mutation, Chemotherapy, Pemetrexed, Erlotinib
Brief summary
Both pemetrexed and erlotinib are second-line treatment options for patients with advanced non-small cell lung cancer. It is controversial that whether it is necessary to detect epidermal growth factor receptor (EGFR) mutation status for the EGFR-targeted therapy after the failure of standard chemotherapy. The role of EGFR gene copy number as a predictive marker remains controversial. Therefore, we investigate the efficacy of erlotinib and pemetrexed as second-line therapy in treating in patients with EGFR wild-type and EGFR FISH-positive advanced lung adenocarcinoma.
Detailed description
Standard first-line treatment for advanced-stage non-small cell lung cancer (NSCLC) usually consists of platinum-based doublet chemotherapy, but progression ultimately occurs for most patients. Second-line treatment options available to patients who suffer failure of first-line treatment include further chemotherapy (docetaxel and pemetrexed) or targeted therapy. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced NSCLC with EGFR mutation. High EGFR gene copy number was associated with great sensitivity and prolonged progression-free survival of NSCLC from EGFR-TKIs. This phase II study was designed to assess the efficacy and safety of erlotinib compared with pemetrexed as second-line treatment for EGFR wild-type and EGFR FISH-positive lung adenocarcinoma.
Interventions
DRUGErlotinib
150 mg Given orally
DRUGPemetrexed
500mg/m2 Given IV
Sponsors
Si-Yu Wang
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
* Histologically or cytologically confirmed Lung adenocarcinoma * Wld-type EGFR * Stage IIIB/IV * Failure to prior chemotherapy * Life expectancy of more than 3 months * Tissue sample desired for genomic study * Age ≥ 18 years * Performance status (WHO) \< 3 * Adequate bone marrow function (absolute neutrophil count \> 1000/mm\^3, platelet count \> 100000/mm\^3, hemoglobin \> 9gr/mm\^3) * Adequate liver (bilirubin \< 1.5 times upper limit of normal and SGOT/SGPT \< 2 times upper limit of normal) and renal function (creatinine \< 2mg/dl) * Presence of two-dimensional measurable disease. The measurable disease should not have been irradiated * Informed consent
Exclusion criteria
* Have previously received pemetrexed or TKIs * Other concurrent uncontrolled illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From the date of randomization to the date of tumour progression or death from any cause, assessed until at least 12 months after randomization. | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Tumor Response | From the date of randomization, assessed every 6 weeks, until at least 12 months after randomization. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Overall Survival | From date of randomization until the date of death from any cause, assessed until at least 12 months after randomization. | — |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Erlotinib at the dose of 150 mg orally once a day continually until progression.
Erlotinib: 150 mg Given orally | 61 |
| Pemetrexed Pemetrexed at the dose of 500mg/m2 IV infusion every 3 weeks until progression.
Pemetrexed: 500mg/m2 Given IV | 62 |
| Total | 123 |
Baseline characteristics
| Characteristic | Erlotinib | Total | Pemetrexed |
|---|---|---|---|
| Age, Continuous | 54.3 years | 54.7 years | 55.1 years |
| ECOG PS 0,1 | 57 participants | 116 participants | 59 participants |
| ECOG PS 2 | 4 participants | 7 participants | 3 participants |
| Sex: Female, Male Female | 21 Participants | 44 Participants | 23 Participants |
| Sex: Female, Male Male | 40 Participants | 79 Participants | 39 Participants |
| Smoking status Current | 39 participants | 79 participants | 40 participants |
| Smoking status Former | 7 participants | 12 participants | 5 participants |
| Smoking status Never | 15 participants | 32 participants | 17 participants |
| Stage IIIB | 4 participants | 10 participants | 6 participants |
| Stage IV | 40 participants | 78 participants | 38 participants |
| Stage Recurrent | 17 participants | 35 participants | 18 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 61 | 43 / 62 |
| serious Total, serious adverse events | 0 / 61 | 0 / 62 |
Outcome results
Primary
Progression-Free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: From the date of randomization to the date of tumour progression or death from any cause, assessed until at least 12 months after randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Progression-Free Survival | 4.1 months |
| Pemetrexed | Progression-Free Survival | 3.9 months |
Secondary
Best Tumor Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: From the date of randomization, assessed every 6 weeks, until at least 12 months after randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Best Tumor Response | Objective response | 12 participants |
| Erlotinib | Best Tumor Response | No objective response | 49 participants |
| Pemetrexed | Best Tumor Response | Objective response | 5 participants |
| Pemetrexed | Best Tumor Response | No objective response | 57 participants |
Secondary
Overall Survival
Time frame: From date of randomization until the date of death from any cause, assessed until at least 12 months after randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Overall Survival | 11.7 months |
| Pemetrexed | Overall Survival | 13.4 months |