GENEVA – For EGFR TKI-naive patients with EGFR-positive non–small cell lung cancer (NSCLC), afatinib appears safe and effective in a “real-world” setting, based on results of a phase 3b study.
Across a diverse population of patients, including those with brain metastases, uncommon mutations, multiple lines of prior therapy, and/or an Eastern Cooperative Oncology Group (ECOG) performance status of 2, afatinib delivered “encouraging” responses, reported lead author Antonio Passaro, MD, PhD, of the European Institute of Oncology in Milan. During his presentation at the European Lung Cancer Conference, Dr. Passaro described the safety profile as “predictable and manageable.”
The findings follow on the heels of the LUX-Lung trials, which showed that afatinib could match the progression-free survival (PFS) achieved with gefitinib, at about 11 months, while beating chemotherapy, which was associated with a PFS of approximately 5-7 months.
“However,” the investigators noted in their abstract, “in real-world practice chemotherapy remains a first-line choice.”
The present study aimed to demonstrate the real-world potential of afatinib across treatment lines, Dr. Passaro said at the meeting, presented by the European Society for Medical Oncology.
The patient population was diverse, with multiple treatment lines represented. The majority of patients (78%) received afatinib as first-line treatment, while smaller groups received the treatment as second-line (17%), or third-line or greater (5%). About one-third of the patients (36%) had an ECOG score of 0, about half (57%) had a score of 1, and a small group (8%) had a score of 2. A minority of patients had brain metastases (17%) and/or uncommon mutations (13%). Patients received 40 mg of afatinib daily; dose reduction to 20 mg was allowed if necessary.
Analysis showed that patients received afatinib for a median of almost 1 year (359 days). Slightly more than half of the patients (54%) got reduced doses because of adverse events, most commonly, diarrhea (25%) and rash (11%). About one out of five patients (22%) discontinued treatment entirely.
Secondarily, the investigators analyzed efficacy, reporting that the objective response rate was 46% and the disease control rate was 86%. During his presentation, Dr. Passaro focused on median time to symptomatic progression (TTSP) and median progression-free survival (PFS), describing these outcomes in relation to patient subgroups. Across all patients, TTSP was 14.9 months and PFS was 13.4 months. Among subgroups, patients receiving afatinib as first-line therapy had the best median PFS, at 13.8 months, which was comparable with those who received the treatment second-line (13.2 months). In contrast, patients receiving afatinib as a third-line treatment or later had noticeably shorter PFS, at 6.6 months. Baseline ECOG performance status showed a similar trend; patients with scores of 0 had a median PFS of 15.4 months, compared with 12.9 months for those with a score of 1, and 6.2 months with a score of 2. Patients with brain metastases fared worse than did those without (PFS 10.1 months vs. 13.9 months), and patients with uncommon mutations had shorter PFS than that of those with common mutations (6.0 months vs. 14.1 months). TTSP durations paralleled the above PFS trends.Boehringer Ingelheim funded the study. The investigators reported financial relationships with Roche, MSD, Bristol-Myers Squibb, AstraZeneca, and others.
SOURCE: Passaro et al. ELCC 2019. .