Afatinib Outperforms Gefitinib in Advanced Non-Small Cell Lung Cancer

By Erik J. MacLaren, PhD

The pan-ErbB inhibitor afatinib (Gilotrif) improves progression-free survival (PFS), time-to-treatment-failure (TTF) rate, and objective response rate (ORR) compared to the first-generation EGFR inhibitor gefitinib (Iressa) as a first-line treatment in patients with EGFR mutation-positive NSCLC, according to results presented at the ESMO Asia 2015 Congress in Singapore.1
Afatinib and gefitinib are both approved for first-line treatment of NSCLC with EGFR mutations based on phase 3 clinical trials that demonstrated their superiority to chemotherapy in that setting. In contrast to gefitinib, a first-generation EGFR tyrosine kinase inhibitor (TKI), afatinib irreversibly blocks members of the ErbB family of receptors, including EGFR, HER2, and ErbB4. In preclinical studies, afatinib has been shown to potently inhibit both wild type and mutated EGFRs, including those with the resistance mutation T790M.
Because acquired resistance frequently develops in patients treated with EGFR TKIs, and previous studies had suggested that afatinib could prolong responses and delay progression, Keunchil Park, MD, PhD, head of the Division of Hematology/Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, and colleagues conducted a head-to-head comparison of afatinib and gefitinib in previously untreated patients.

First-line afatinib treatment significantly reduced the risk of lung cancer progression by 27% versus gefitinib. —Keunchil Park, MD, PhD

A total of 319 patients were randomized to receive 40 mg daily afatinib (n = 160) or 250 mg daily gefitinib (n = 159). Baseline characteristics were similar in both treatment groups. Just over half of the participants were Asian (58.8% and 55.3%, respectively), and the most common EGFR mutation was an exon 19 deletion, which was found in 57.5% of the afatinib group and 58.5% of the gefitinib group.
At the conference, Dr. Park highlighted the positive results for progression-free survival (PFS). “First-line afatinib treatment significantly reduced the risk of lung cancer progression by 27% versus gefitinib,” he said. “Interestingly, the improvement in PFS became more pronounced over time, with a significantly higher proportion of patients alive and progression-free at 18 months (27% vs 15%; P = 0.018) and 24 months (18% vs 8%; P = 0.018), showing a greater long-term benefit of using the irreversible ErbB family blocker afatinib.”
In addition to the promising PFS results, response rates were also higher for patients in the afatinib arm (70%) than those receiving gefitinib (56%), and the median duration of response was 10.1 months for afatinib compared to 8.4 months for gefitinib. Discontinuation due to adverse events was 6.3% for both arms, indicating, from a practical standpoint, a comparable safety profile for both drugs.
“Based on these results, I would consider afatinib as the EGFR TKI of choice for the first-line treatment for patients with EGFR mutation-positive NSCLC,” noted Dr. Park.

1. Park K, Tan E, Zhang L, et al. Afatinib (A) vs gefitinib (G) as first-line treatment for patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations: results of the global, randomized, open-label, Phase IIb trial LUX-Lung 7 (LL7). Paper presented at: 2015 ESMO Asia Congress; December 18-21, 2015; Singapore.