Gilotrif Gains Approval for NSCLC

Gilotrif (afatinib) was approved for the treatment of advanced squamous cell non—small cell lung cancer (NSCLC) after progression on platinum-based chemotherapy, said Boehringer Ingelheim, the manufacturer of the irreversible EGFR inhibitor.

The approval was based on results from the phase 3 LUX-Lung 8 study, which compared second-line Gilotrif with Tarceva (erlotinib) in patients with advanced squamous cell carcinoma of the lung. In the study, Gilotrif reduced the risk of death by 19 percent and disease progression by 18 percent compared with Tarceva.

“The overall survival data and significant delay in lung cancer progression seen in the global head-to-head phase 3 trial demonstrated that Gilotrif is an effective new treatment option in this patient population,” LUX-Lung 8 clinical trial investigator Shirish Gadgeel, MD, leader of the Thoracic Oncology Multidisciplinary Team at the Karmanos Cancer Center, said in a statement.

The open-label LUX-Lung 8 study included 795 patients with stage 3B or 4 squamous cell NSCLC who had progressed following at least four cycles of platinum-based-chemotherapy. The 398 participants were randomized in a one to one ratio to receive Gilotrif at 40 mg daily or 150 mg of Tarceva per day for 397 patients until progression. The primary outcome measure was progression-free survival (PFS) and overall survival (OS) was the main secondary endpoint.

OS was 7.9 months versus 6.8 months with Gilotrif versus Tarceva, respectively. PFS was 2.4 months with Gilotrif compared to 1.9 months with Tarceva. The objective response rates were similar between the 2 arms, at 6 percent and 11 percent.

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

More patients reported improved overall health-related quality-of-life with Gilotrif than Tarceva (36 percent vs 28 percent).

Gilotrif is a an irreversible ErbB family blocker that specifically inhibits EGFR (ErbB1), HER2 (ErbB2) and ErbB4.

In 2013, the FDA approved Gilotrif 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 3 LUX-Lung 3 trial, which involved 345 patients with stage 3B/4 lung adenocarcinoma who were randomly assigned to treatment with either Gilotrif or a combination of Platinol-AQ (cisplatin) and Alimta (pemetrexed). Patients in the Gilotrif arm experienced a median PFS of 11.1 months compared with 6.9 months in the Platinol-AQ and Alimta arm.

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 Gilotrif experienced a median PFS of 13.6 months compared with 6.9 months in the Platinol-AQ and Alimta arm.

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

“We are pleased to bring a proven therapy to patients suffering from advanced squamous cell carcinoma of the lung who have progressed despite chemotherapy,” Sabine Luik, senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim, said in a statement. “This approval is further evidence of Boehringer Ingelheim’s strong commitment to bringing new treatment options to the lung cancer community.”