Head-to-head Phase III trial demonstrates superior progression-free survival for afatinib compared to erlotinib in patients with advanced squamous cell carcinoma of the lung

Phase III data from the LUX-Lung 8 trial, the first study to directly compare the efficacy of two different targeted agents in patients with advanced squamous cell carcinoma (SCC) of the lung, demonstrated superior progression-free survival (PFS) of afatinib compared to erlotinib.

Afatinib, an irreversible ErbB Family Blocker, showed significant improvement across several measures of efficacy, in particular for the primary endpoint of PFS compared to erlotinib in patients who failed first-line chemotherapy.

Eligible patients with stage IIIB/IV SCC were randomized 1:1 to receive afatinib (40 mg/day; 50 mg/day from Cycle 2 for patients meeting adverse events criteria) or erlotinib (150 mg/day) until disease progression. All patients had progressed after ≥ 4 cycles of platinum-based doublet chemotherapy and had not received prior EGFR tyrosine kinase inhibitors (TKIs). The primary endpoint was PFS (RECIST 1.1) as assessed by independent radiological review (IRR), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.

LUX-Lung 8 results demonstrated that afatinib significantly reduced the risk of disease progression by 18% when compared to erlotinib and delayed tumour growth (median PFS by independent review: 2.4 vs. 1.9 months, HR [95% CI]: 0.82 [0.68–1.00]; p = 0.0427). In addition, afatinib showed an improvement in the secondary endpoint of DCR (46% vs. 37%). The ORR was numerically higher with afatinib compared to erlotinib (5% vs. 3%), however, this difference was not statistically significant. There was a longer duration of overall response seen with afatinib vs erlotinib (see slides). Moreover, favourable trends were noted in delaying the worsening of lung cancer symptoms and global health status/quality of life. The proportion of patients reporting improvement in cough and global health status/quality of life, respectively, was significantly higher with afatinib versus erlotinib.

The overall rate of severe (≥ grade 3) and serious adverse events was comparable between both therapies. Incidence of severe adverse events was 50.2% in patients treated with afatinib compared to 49.1% with erlotinib. A higher incidence of ≥ grade 3 diarrhoea and stomatitis was observed in patients treated with afatinib compared to erlotinib (≥ grade 3 diarrhoea: 9% vs. 2%; stomatitis: 3% vs. 0%), while there was a higher incidence of ≥ grade 3 rash/acne observed with erlotinib compared to afatinib (9% vs. 6%).

In summary, the results of LUX-Lung 8 demonstrate the progression-free survival benefit for afatinib over erlotinib in advanced squamous cell carcinoma of the lung, a disease with poor prognosis for which there are currently limited treatment options. Furthermore, the treatment also resulted in a favourable impact on patients’ overall health and quality of life. Overall survival data were immature at the time of presentation and are eagerly awaited.

Reference

Goss G, Filp E, Cobo M, et al. A randomized, open-label, phase III trial of afatinib (A) vs erlotinib (E) as second-line treatment of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung following first-line platinum-based chemotherapy: LUX-Lung 8 (LL8). Presented at ESMO 2014; Abstract 1222O.