Afatinib plus Paclitaxel versus chemotherapy in patients with metastatic non-small cell lung cancer progressed on Erlotinib / Gefitinib and Afatanib
Improved disease control with continuation of EGFR inhibition beyond progression has been suggested in retrospective / non-randomized studies, however, this has yet to be prospectively evaluated in a randomized trial.
LUX-Lung 5 ( LL5 ) is a randomized trial, which has assessed the efficacy of continuation of the irreversible ErbB family blocker, Afatinib ( Giotrif ), beyond progression with the addition of Paclitaxel in non-small cell lung cancer ( NSCLC ) patients with prior benefit from reversible EGFR tyrosine kinase inhibitors ( Erlotinib / Gefitinib; E/G ) and Afatinib.
In this open-label, global phase III trial, patients with non-small cell lung cancer who had failed greater than or equal to 1 line of investigator’s choice chemotherapy ( CT ) and Erlotinib / Gefitinib ( after 12 weeks or more treatment ) were treated with Afatinib ( 50 mg/day ) in Part A ( n=1154 ).
Upon progression, those with 12 weeks or more on Afatinib were eligible to be randomized 2:1 to Afatinib plus Paclitaxel ( 40 mg/day; 80 mg/m2/week ) or single agent investigator’s choice chemotherapy in Part B.
Primary endpoint was progression-free survival ( PFS ). Secondary endpoints included objective response rate ( ORR ), overall survival ( OS ), and safety.
A total of 202 patients were randomized ( Afatinib plus Paclitaxel, n=134; chemotherapy, n=68 ) and baseline characteristics were well balanced ( median age 60 years, females 49%, ECOG PS 0–1 91% overall ).
A statistically significant improvement in progression-free survival was observed on Afatinib plus Paclitaxel vs chemotherapy arm ( median 5.6 vs 2.8 months; hazard ratio, HR=0.60; 95% CI 0.43, 0.85; p=0.003 ).
Objective response rate was also significantly higher in Afatinib plus Paclitaxel arm vs chemotherapy ( 32.1% vs 13.2%; p=0.005 ).
Overall survival was similar in both arms 12.2 vs 12.2 months, HR=1.00 ( 95% CI 0.70, 1.43; p=0.994 ).
Most common related adverse events with Afatinib plus Paclitaxel vs chemotherapy were diarrhea ( 53.8% vs 6.7% ), alopecia ( 32.6% vs 15.0% ) and asthenia ( 27.3% vs 28.3% ).
In conclusion, continued ErbB family blockade with Afatinib with the addition of Paclitaxel significantly improves progression-free survival and ORR vs chemotherapy alone in heavily pretreated patients with acquired resistance to Erlotinib / Gefitinib and progression on Afatinib monotherapy.
Adverse reactions were considered manageable.
The data support that tumors progressing on Erlotinib / Gefitinib and Afanitib continue to depend on signalling through the receptors of the ErbB family and can benefit from continuous ErbB family blockade with Afatinib. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Meeting, 2014
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