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Pooled analysis of LUX-Lung 3 and LUX-Lung 6 comparing Afatinib with chemotherapy: overall survival in patients with advanced non-small cell lung cancer harboring common EGFR mutations


Afatinib ( Giotrif ) is an oral, irreversible ErbB family blocker of EGFR, HER2, ErbB3 and ErbB4 signalling. LUX-Lung 3 ( LL3 ) has compared Afatinib with Cisplatin / Pemetrexed in 345 patients recruited globally and LUX-Lung 6 ( LL6 ) compared Afatinib with Gemcitabine / Cisplatin in 364 Asian patients.

The primary analysis ( 2012 ) showed improved progression-free survival ( PFS ) with Afatinib versus chemotherapy ( CT ) in the overall EGFR mutation positive population ( hazard ratio, HR=0.58 [ LL3 ], HR=0.28 [ LL6 ] ) and patients with common ( Del19/L858R ) EGFR mutation ( HR=0.47 [ LL3 ], HR=0.25 [ LL6 ] ).

The FDA ( Food and Drug Administration ) has approved Afatinib for the first-line treatment of pts with advanced NSCLC harboring common EGFR mutation.

A pooled analysis of mature overall survival data among such patients was presented.

Treatment-naïve patients with EGFR mutation stage IIIB/IV non-small cell lung cancer were randomized 2:1 to 40 mg Afatinib or up to 6 cycles of standard chemotherapy and stratified by EGFR mutation and race ( LL3 ).

The primary endpoint was progression-free survival, with overall survival as a key secondary endpoint.

The pooled analysis included 631/709 patients randomized into LL3 and LL6 with common EGFR mutation ( Del19=355, L858R=276 ); 419 patients received Afatinib and 212 received chemotherapy.

At the time of analysis ( January 2014 ), 404 ( 64% ) patients had died. Median follow-up for overall survival was 36.5 months.

Following progression, 78% of patients received subsequent systemic therapies ( median of 3 regimens ); 68% in the chemotherapy group received EGFR tyrosine-kinase inhibitors ( TKIs ) and 70% in the Afatinib group received chemotherapy.

Overall survival was significantly improved with Afatinib versus chemotherapy ( median 27.3 vs 24.3 months, HR=0.81 [ CI 0.66, 0.99; p=0.037 ] ).
Individual hazard ratios for overall survival in LL3 and LL6 were consistent with the pooled analysis.

Among Del19 patients the HR=0.59 ( CI 0.45, 0.77; p less than 0.001 ) and in L858R patients the HR=1.25 ( CI 0.92, 1.71; p=0.160 ).

Updated progression-free survial and safety findings were consistent with earlier primary reports.

In conclusion, the pooled analysis has revealed that first-line Afatinib significantly improves overall survival in patients with advanced non-small cell lung cancer harboring common EGFR mutation ( Del19 / L858R ) compared with chemotherapy.
This is the first analysis to show that genotype-directed therapy for EGFR mutation patients can improve survival. ( Xagena )

Source: American Society of Clinical Oncology ( ASCO ) Meeting, 2014

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