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FDA Accepts Afatinib Application for Squamous Cell Lung Cancer

Jason M. Broderick @jasoncology
Published: Wednesday, Aug 26, 2015

Jörg Barth

Dr Jörg Barth

The FDA has accepted an application for afatinib (Gilotrif) as a treatment for patients with squamous cell non–small cell lung cancer (NSCLC) following progression on chemotherapy, according to Boehringer Ingelheim, the manufacturer of the irreversible EGFR inhibitor. Afatinib was also granted orphan drug status.

Boehringer reported that a separate regulatory filing for afatinib in the same setting was accepted by the European Medicines Agency.

The two applications were based on results from the phase III LUX-Lung 8 study, which compared second-line afatinib with erlotinib (Tarceva) in patients with advanced squamous cell carcinoma of the lung. In the study, afatinib reduced the risk of both disease progression and death by 19%, compared with erlotinib.

“Working with the US and EU regulatory authorities marks the next stage in our journey to hopefully provide patients with a new, oral treatment for squamous cell carcinoma of the lung, a condition with an extremely poor prognosis. This is an encouraging prospect for Boehringer Ingelheim, as we remain fully dedicated to improving and extending the lives of patients with different types of lung cancer,” said Dr Jörg Barth, corporate senior vice president, therapy area head oncology, Boehringer Ingelheim.

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 a an irreversible ErbB family blocker that specifically inhibits EGFR (ErbB1), HER2 (ErbB2), and ErbB4. In 2013, the FDA approved afatinib as a frontline treatment for patients with metastatic NSCLC whose tumors harbor EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. The FDA concurrently approved the therascreen EGFR RGQ PCR Kit (QIAGEN) for detection of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

The approval was based on results from the phase III LUX-Lung 3 trial, which involved 345 patients with stage IIIB/IV lung adenocarcinoma who were randomly assigned to treatment with either afatinib or a combination of cisplatin and pemetrexed. Patients in the afatinib arm experienced a median PFS of 11.1 months compared with 6.9 months in the cisplatin and pemetrexed arm (HR, 0.58; 95% CI, 0.43-0.78; P = .001).

The difference in survival was more pronounced in patients who expressed either an exon 19 deletion or an exon 21 L858R substitution. Patients with those specific mutations who received afatinib experienced a median PFS of 13.6 months compared with 6.9 months in the cisplatin and pemetrexed arm (HR, 0.47; 95% CI, 0.34-0.65; P = .001).

The most common treatment-related adverse events experienced by patients in the study who received afatinib were diarrhea, rash or acne, and stomatitis.

If approved for advanced squamous carcinoma, afatinib would be competing with the anti–PD-1 agent nivolumab (Opdivo) in this setting. In March, the FDA approved nivolumab for the treatment of patients with advanced squamous NSCLC who have progressed on or after platinum-based chemotherapy. The approval was based on data from the phase III CheckMate-017 trial in which nivolumab improved OS by 41% versus docetaxel in patients with advanced squamous cell NSCLC (9.2 vs 6.0 months; HR, 0.59; 95% CI, 0.44-0.79; P = .00025).


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.



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