Combination of Cetuximab With Afatinib for Patient With EGFR Mutated Lung Cancer (ACE-Lung)

Intergroupe Francophone de Cancerologie Thoracique

Status and phase: Completed; Phase 2

Conditions: Non Small Cell Lung Cancer

Treatments: Drug: Cetuximab; Drug: Afatinib

Study type: Interventional

Funder types: Other

Identifiers

NCT02716311

IFCT-1503

Details and patient eligibility

About

Until recently, the first line treatment of metastatic Non Small Cell Lung Cancer (NSCLC) was a platine-based chemotherapy. It has been changed by the discovery of EGFR (Epidermal Growth Factor Receptor) mutations and associated treatment with Tyrosine Kinase Inhibitor (TKI) of EGFR. The superiority of EGFR TKI over chemotherapy for EGFR mutated patients has been proved in several phase III trials with gefitinib, erlotinib or afatinib.

Nevertheless, all patients will progress after 9 to 12 months of treatment due to the appearance of a treatment resistance.

Afatinib is an irreversible EGFR TKI. It binds to its receptor permanently.Contrary to erlotinib and gefitinb which inhibits only EGFR, afatinib inhibits the kinase activity of all HER family (Human Epidermal growth factor Receptor). Nevertheless, there is no proof that afatinib delay the appearance of resistance.

Cetuximab is a monoclonal antibody which binds specifically with EGFR. The double inhibition of EGFR by afatinib and cetuximab has demonstrated its efficacy in pre-clinical models. The hypothesis of this study is that the combination between cetuximab and afatinib will permit to delay or decrease the appearance of resistances.

Enrollment: 118 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Principal Inclusion Criteria:

• Stage III or IV NSCLC, non irradiable non operable
• Non squamous NSCLC histologically or cytologically confirmed
• No previous treatment of NSCLC
• EGFR mutation (exon 19 deletion, L858R mutation, G719X , L861Q or S768I mutations or exon 19 insertion)
• Presence of at least one lesion that can be measured
• PS 0 or 1

Principal Exclusion Criteria:

• Symptomatic brain metastasis or requiring immediate radiotherapy
• T790M mutation or exon 20 insertion
• Radiotherapy less than 2 weeks prior randomization including symptomatic radiotherapy
• Interstitial pneumopathy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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118 participants in 2 patient groups

Afatinib

Other group

Description:

Afatinib 40 mg/d until progression

Treatment:

Drug: Afatinib

Afatinib + cetuximab

Experimental group

Description:

Afatinib 40 mg/d until progression + cetuximab 500 mg/m² every 2 weeks during 6 months (beginning at D15 at 250 mg/m²)

Treatment:

Drug: Cetuximab

Drug: Afatinib