Treatment options for patients with advanced squamous cell carcinoma (SCC) of the lung progressing after platinum-based chemotherapy are limited.a Overexpression of EGFR, ErbB, receptors and the dysregulation of their downstream pathways are implicated in SCC pathobiology. Primary analysis of the global phase 3 LUX-Lung 8 trial showed significantly better progression-free survival (PFS) with afatinib (A) compared with erlotinib (E).b In this presentation, Soria and colleagues reported overall survival (OS) and updated PFS data.c A total of 800 patients with stage IIIB/IV disease were randomized 1:1 to receive A (40 mg/day) or E (150 mg/day) until disease progression. The primary endpoint was PFS; a key secondary endpoint was OS. Other endpoints included objective response (ORR), disease control rate (DCR), patient reported outcomes (PRO), and safety. OS was significantly better with A (n = 398) versus E (n = 397), with a 19% reduced risk of death (median 7.9 vs 6.8 months; HR [95% CI] 0.81 [0.69–0.95]; P = 0.008). Significant differences in OS were seen at 6 (63.6 vs 54.6%; P = 0.010), 12 (36.4 vs 28.2%; P = 0.016) and 18 (22.0 vs 14.4%; P = 0.013) months. PFS (median 2.6 vs 1.9 months; HR [95% CI] 0.81 [0.69–0.96]; P = 0.010), ORR (5.5 vs 2.8%; P = 0.055) and DCR (50.5 vs 39.5%; P = 0.002) were all better for A vs E. Subgroup analysis revealed that the superiority of A over E was observed across age, gender, race, smoking history, and histology subgroups, as well as history of best response to first-line therapy. DCR was significantly better in the A group compared with the E group (50.5% vs. 39.5%; P = 0.002). More patients had improved global health status and quality of life (35.7 vs 28.3%; P = 0.041), improved cough (43.4 vs 35.2%; P = 0.029) and dyspnea (51.3 vs 44.1%; P = 0.061) with A versus E. There was no correlation between EGFR mutations and PFS or OS outcomes. Adverse event (AE) profiles were comparable (Grade ? 3 AEs: 57.1 and 57.5% for A vs E) with a higher incidence of drug-related Grade 3/4 diarrhea (9.9/0.5 vs 2.3/0.3%), Grade 3 stomatitis (4.1 vs 0%) with A and a higher incidence of Grade 3 rash/acne with E (5.9 vs 10.4%).
In this largest phase 3 trial of second-line treatment of SCC of the lung, the authors concluded that A significantly improved OS versus E. With a manageable AE profile, added quality of life benefit, and symptom control seen in LL8, the authors concluded that A should be preferred over E for these patients. However, in an analysis of this presentation, the use of EGFR inhibitors as the preferred second-line treatment option for SCC of the lung was questioned, especially in view of the recent FDA approvals of ramucirumab and nivolumab, and the reported response rates with ramucirumab plus docetaxel, and the potentially practice-changing results with nivolumab in this patient population.d-f
