HER2 (erbB-2/neu) is a member of the erbB receptor tyrosine kinase family. ERBB2 gene which encodes human epidermal growth factor 2 (HER2) is a major proliferative driver activating downstream signaling through PI3K-AKT and MEK-ERK. HER2 overexpression or gene amplification is associated with sensitivity to trastuzumab and lapatinib in breast cancer. Among actual lung cancer biomarker, HER2 remains apart. HER2 involvement is known for a long time but clinical research has been stopped for many years since the first clinical trials in unselected patients were negative. Recently trastuzumab + pertuzumab + docetaxel has been tested for first-line treatment of HER2-positive metastatic breast cancer (CLEOPATRA trial). Analysis of the primary end point showed that patients who received pertuzumab, trastuzumab, and docetaxel (pertuzumab group) had a significantly longer median progression-free survival, as assessed by independent reviewers an did those who received placebo, trastuzumab, and docetaxel (control group) (hazard ratio favoring the pertuzumab group, 0.62). There is thus a strong rational for treating HER2 mutated lung cancer patient with these drugs.
Name: pertuzumab + trastuzumab + docetaxel
Description: Cycle 1 : D1 : pertuzumab 840 mg, D2 : trastuzumab 8 mg/kg + docetaxel 75 mg/m² Subsequent cycle : D1 : pertuzumab 420 mg + trastuzumab 6 mg/kg + docetaxel 75 mg/m²Type: Drugpertuzumab + trastuzumab + docetaxel
Description: Percentage of patient with confirmed objective response rate with RECIST 1.1
Measure: Objective Response Rate Time: 6 weeks (confirmation needed at 12 weeks)Description: Time from enrollment until death due to any cause
Measure: Overall Survival Time: About 24 monthsDescription: time from enrollment to first observation of progression (according to RECIST v1.1) or date of death (from any cause)
Measure: Progression-free survival Time: About 24 monthsDescription: Time from documentation of tumor response to disease progression.
Measure: Duration of response Time: About 24 monthsSingle Group Assignment
There are 2 SNPs
Not suitable for radiation, inoperable stage III or stage IV 4. HER2 exon 20 mutation or insertion among which: in-frame insertions in exon 20 between codons 775 and 881 including the 12bp insertion with a duplication / insertion of 4 amino acids (YVMA) at codon 775, the 3bp insertion with a complex insertion-substitution G776>VC and point mutations L755S and G776C. --- L755S --- --- G776C ---
Not suitable for radiation, inoperable stage III or stage IV 4. HER2 exon 20 mutation or insertion among which: in-frame insertions in exon 20 between codons 775 and 881 including the 12bp insertion with a duplication / insertion of 4 amino acids (YVMA) at codon 775, the 3bp insertion with a complex insertion-substitution G776>VC and point mutations L755S and G776C. --- L755S ---