SUMMARY: Lung cancer is the second most common cancer in both men and women and accounts for about 13% of all new cancers and 27% of all cancer deaths. It is the leading cause of cancer death among both men and women. The American Cancer Society estimates that over 221,200 new cases of lung cancer will be diagnosed in the United States in 2015 and over 158,000 patients will die of the disease. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Of the three main subtypes of Non Small Cell Lung Cancer (NSCLC), 30% are Squamous Cell Carcinomas (SCC), 40% are Adenocarcinomas and 10% are Large cell carcinomas.
Non Small Cell Lung Cancer patients with squamous cell histology have been a traditionally hard- to-treat patient group, with less than 5% of patients with advanced SCC, surviving for five years or longer. Some of the advanced NSCLC tumors are dependent on the Epidermal Growth Factor Receptor (EGFR) for cell proliferation and survival, regardless of EGFR mutation status. TARCEVA® (Erlotinib) is a reversible EGFR Tyrosine Kinase Inhibitor and is presently approved by the FDA for the treatment of locally advanced or metastatic NSCLC, after failure of at least one prior chemotherapy regimen. GILOTRIF® (Afatinib) is an oral, irreversible blocker of the ErbB family which includes EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4. This kinase inhibitor is indicated for the first line treatment of patients with metastatic NSCLC, whose tumors have Epidermal Growth Factor Receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.
The LUX-Lung 8 is a phase III trial in which 795 patients with Stage IIIB/IV Squamous Cell Carcinoma of the lung who had progressed on first line platinum based doublet therapy, were randomized 1:1 to receive GILOTRIF 40 mg PO daily (N=398) or TARCEVA 150 mg PO daily (N=397). Treatment was given until disease progression. The median age was 65 years. Majority of the patients were male, caucasian and ex-smokers. The Primary endpoint was Progression Free Survival (PFS) and Secondary endpoints included Overall Survival (OS), Objective Response Rate (ORR), Disease Control Rate (DCR), patient reported outcomes and safety. The Primary endpoint of Progression Free Survival (PFS) was met and reported in 2014 and favored GILOTRIF® over TARCEVA®. The authors in this analysis reported the Overall Survival data, as well as updated data on Progression Free Survival and other Secondary endpoints. The median Overall Survival was 7.9 months with GILOTRIF® and 6.8 months with TARCEVA® (HR=0.81; P=0.008). This meant a 19% reduction in the risk of death with GILOTRIF® when compared to TARCEVA® and this survival advantage was consistent across all time points. The updated median Progression Free Survival for GILOTRIF® was 2.6 months vs 1.9 months for TARCEVA® (HR=0.81; P=0.01). The Disease Control Rate was 50.5% for GILOTRIF® and 39.5% with TARCEVA® (P=0.002). Based on patient reported outcomes, symptoms including cough and dyspnea were better with GILOTRIF® compared to TARCEVA®. Incidence of severe adverse events was similar with both therapies, with patients on GILOTRIF® experiencing more grade 3 diarrhea and stomatitis and patients receiving TARCEVA® experiencing more grade 3 rash. The authors concluded that GILOTRIF® should be the TKI of choice in the second line treatment of patients with Squamous Cell Carcinoma of the lung, as it significantly improves Overall Survival, Progression Free Survival, Disease Control Rate and symptom control, with manageable toxicities, when compared to TARCEVA®. Afatinib (A) vs erlotinib (E) as second-line therapy of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung following platinum-based chemotherapy: Overall survival (OS) analysis from the global phase III trial LUX-Lung 8 (LL8). Soria J, Felip E, Cobo M, et al. J Clin Oncol 33, 2015 (suppl; abstr 8002)
