CHMP Recommends Afatinib for Second-Line NSCLC

Afatinib has received a positive opinion from the CHMP, recommending European approval for use in patients with advanced squamous cell non–small cell lung cancer following progression on platinum-based chemotherapy.

Mehdi Shahidi, MD

Afatinib (Giotrif, EU; Gilotrif, US) has received a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) as a treatment for patients with advanced squamous cell non—small cell lung cancer (NSCLC) following progression on platinum-based chemotherapy, according to Boehringer Ingelheim, the manufacturer of the irreversible EGFR inhibitor.

The CHMP opinion, which recommends that the treatment should gain approval from the European Medicines Agency in this setting, is based on data from the phase III LUX-Lung 8 trial. In the study, second-line afatinib reduced the risk of both disease progression and death by 19%, compared with erlotinib (Tarceva) in patients with advanced squamous cell carcinoma of the lung.

“Despite recent advances in the treatment of squamous cell lung cancer, this disease remains challenging to treat. We are pleased to receive this positive opinion from the CHMP for afatinib; not only does it represent the potential availability of the first oral treatment option specifically approved for patients with squamous cell lung cancer, it also confirms the positive profile of afatinib, a second-generation EGFR targeting agent, when compared to a first-generation agent,” Mehdi Shahidi, MD, medical head, Solid Tumour Oncology, Boehringer Ingelheim, said in a statement.

The open-label LUX-Lung 8 study included 795 patients with stage IIIB or IV squamous cell NSCLC who had progressed following ≥4 cycles of platinum-based-chemotherapy. Participants were randomized in a 1:1 ratio to receive afatinib (n = 398) at 40 mg daily or 150 mg of erlotinib per day (n = 397) until progression. The primary outcome measure was progression-free survival (PFS) and overall survival (OS) was the main secondary endpoint.

At a median follow-up of 18.4 months, OS was 7.9 months versus 6.8 months with afatinib versus erlotinib, respectively (HR, 0.81; 95% CI, 0.69-0.95; P = .0077). PFS was 2.6 months with afatinib compared to 1.9 months with erlotinib (HR, 0.81; 95% CI, 0.69-0.96; P = .0103). The objective response rates were similar between the 2 arms, at 6% and 11%, respectively (P = .0551).

All-grade adverse event rates were comparable between treatment arms. Fifty-seven percent of patients in each cohort experience grade ≥3 adverse events. Rates of grade 3 stomatitis (4% vs none) and grade 3 diarrhea (10% vs 2%) were higher in patients receiving afatinib versus erlotinib. Incidence of grade 3 rash or acne was higher with erlotinib at 10% versus 6% with afatinib.

More patients reported improved overall health-related quality-of-life with afatinib than erlotinib (36% vs 28%).

Afatinib is an irreversible ErbB family blocker that specifically inhibits EGFR (ErbB1), HER2 (ErbB2), and ErbB4. The drug is approved in Europe and the United States for the first-line treatment of EGFR-positive patients with advanced NSCLC. The FDA is also currently reviewing the LUX-Lung 8 data for US approval of afatinib in the second-line squamous NSCLC setting.

The robust ongoing LUX-Lung program continues to evaluate afatinib in multiple settings. Data from the phase IIb LUX-Lung 7 trial were presented at the ESMO Asia Congress in December 2015. In the study, frontline afatinib reduced the risk of progression or death by 27% compared with gefitinib (Iressa) in patients with EGFR-mutant NSCLC.

Soria J-C, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015:16(8);897-907.