Afatinib (A) vs erlotinib (E) as second-line treatment of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung: LUX-Lung 8 (LL8), a phase III trial

Background: A is an irreversible ErbB family blocker that has shown clinical activity in pts with SCC of the head/neck and lung. This phase III trial prospectively compared A and E in pts with SCC of the lung following failure of platinum-based first-line chemotherapy.Methods: Pts with stage IIIB/IV SCC were randomized 1:1 to receive A (40 mg/day; n=335) or E (150 mg/day; n=334) until progression. The primary endpoint was PFS. Secondary endpoints were OS, ORR, DCR, patient-reported outcomes (PROs) and safety.Results: Baseline characteristics were well balanced between arms. Median PFS was significantly higher for A than E (2.4 vs 1.9 mths; HR [95% CI]: 0.82 [0.68–1.00]; p=0.04). Also, ORR (4.8 vs 3.0%; p=0.23) and DCR (45.7 vs 36.8%; p=0.02) were higher with A vs E. Overall AE profile was comparable (≥G3 AEs: 50.2 and 49.1%, serious AEs: 39.2 and 38.0% for A and E, respectively) with higher incidence of drug-related ≥G3 diarrhoea (9.7 vs 2.4%) and G3 stomatitis (3.3 vs 0%) with A and higher incidence of G3 rash/acne with E (5.5 vs 9.0%). AEs leading to treatment discontinuation were comparable (17.9 vs 13.9%). More pts had improved global health status/quality of life (36.4 vs 27.1%; p=0.03) with A than E. Changes in mean scores over time significantly favoured A vs E for cough, dyspnoea and pain. Primary OS, updated PFS, response and PRO data will be presented at the meeting.Conclusions: LL8 is the largest prospective trial comparing A vs E, an approved TKI in pts with pretreated SCC. PFS, DCR and improved global health status were significantly better for A than E. AEs were comparable and manageable.