Biomarker analyses of tumour samples from the ZODIAC study indicate that epidermal growth factor receptor (EGFR) gene copy number and mutation status may help identify the non-small-cell lung cancer (NSCLC) patients most likely to benefit from treatment with vandetanib plus docetaxel.
Study author Anderson Ryan (University of Oxford, UK) and colleagues explain that the randomised phase III ZODIAC study showed that adding vandetanib (100 mg/day) to docetaxel (75 mg/m2 every 21 days) improved progression-free survival (PFS) but not overall survival (OS) versus docetaxel alone in unselected patients with previously treated locally advanced or metastatic NSCLC.
The present prospective biomarker analysis investigated whether EGFR gene amplification, mutation and protein expression, and KRAS gene mutation predicted which patients benefit from vandetanib as a second-line treatment for NSCLC.
A total of 431 pretreatment tumour samples from the original study population were available for analysis of at least one of the planned biomarkers; 88% were positive for EGFR protein expression by immunohistochemistry (EGFR IHC+), 35% had increased EGFR gene copy number on fluorescent in situ hybridisation (EGFR FISH+), 14% were positive for EGFR mutations (EGFR MT+) and 13% were positive for KRAS gene mutations (KRAS MT+).
The researchers found that patients in the EGFR FISH+ subgroup who received vandetanib plus docetaxel were likely to have significantly better PFS (hazard ratio [HR]=0.61) and OS (HR=0.48) and were significantly more likely to have a better objective response rate (ORR; odds ratio [OR]=3.90) than those who received docetaxel alone.
Similarly, patients with EGFR MT+ tumours were more likely to benefit in terms of PFS, OS and ORR with the addition of vandetanib to docetaxel, with respective HRs of 0.51 and 0.46 and an OR of 3.34 versus docetaxel alone.
By contrast, neither EGFR FISH-, EGFR MT- nor KRAS+ patients appeared to benefit from vandetanib treatment, while KRAS MT- patients showed some benefit (PFS HR=0.75, OS HR=0.87, ORR OR=1.88), but at a similar level to that seen in the unselected study population.
Ryan et al note that a post-hoc analysis demonstrated that patients with EGFR MT- tumours benefitted from vandetanib treatment if the tumours were EGFR FISH+, but not if they were EGFR FISH-, “indicating that the benefits of vandetanib in EGFR FISH+ tumors are not restricted to patients with concurrent EGFR mutations.”
They conclude in the Annals of Oncology that their study “raises the possibility that the combination of docetaxel chemotherapy and an EGFR TKI [tyrosine kinase inhibitor] in patients with EGFR FISH+ and/or EGFR MT+ tumors may be worthy of further investigation since previous studies that suggested no benefit of EGFR in combination with chemotherapy were in unselected patients.”
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