Experience with afatinib in patients with non-small cell lung cancer progressing after clinical benefit from gefitinib and erlotinib

Abstract

Background: Afatinib, an irreversible ErbB family blocker, demonstrated superiority to chemotherapy as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is also active in patients progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs). We report the results of a large cohort of NSCLC patients receiving afatinib within a compassionate-use program (CUP).

Patients and methods: Patients with advanced NSCLC progressing after one line or more of chemotherapy and one line or more of EGFR-TKI treatment with either an EGFR mutation or documented clinical benefit were enrolled. Data collection was not monitored or verified by central review. The intention of this CUP was to provide controlled preregistration access to afatinib for patients with life-threatening diseases and no other treatment option.

Results: From May 2010 to October 2013, 573 patients (65% female; median age: 64 years [range: 28-89 years]) were enrolled, with strong participation of community oncologists. Comorbidities were allowed, including second malignancies in 11% of patients. EGFR mutation status was available in 391 patients (72%), and 83% tested mutation positive. Median time to treatment failure (TTF) of 541 patients treated with afatinib was 3.7 months (range: 0.0 to >29.0 months). Median TTF was 4.0 and 2.7 months in patients with adenocarcinomas and squamous cell carcinomas, respectively, and 4.6 months in patients with EGFR-mutated NSCLC. Adverse events were generally manageable.

Conclusion: Afatinib was able to be given in a real-world setting to heavily pretreated patients with EGFR-mutated or EGFR-TKI-sensitive NSCLC. Acknowledging the constraints of data collection in a CUP, afatinib appears to be safe and to confer some clinical benefit in this population.

Keywords: Afatinib; Epidermal growth factor receptor; Erlotinib; Gefitinib; Non-small cell lung cancer.

Figure 1.

Fraction of patients with first-line treatment with gefitinib or erlotinib (patients with EGFR-mutated cancer) and overall rate of EGFR testing. The actual numbers of tested patients and patients diagnosed per year are also given. Abbreviation: EGFR, epidermal growth factor receptor.

Figure 2.

Time to treatment failure with afatinib for the entire cohort (A), in relation to lung cancer histology (B), and in relation to EGFR mutational status (C). Abbreviation: EGFR, epidermal growth factor receptor.

Figure 3.

Prevalence and impact of afatinib dose modifications. (A): Relative distribution of afatinib dose per cycle (cycles 1–12). (B): Median time to treatment failure in relation to afatinib dose calculated for each cycle (cycles 1–7).

Figure 4.

Time to treatment failure in relation to immediate pretreatment (chemotherapy followed by afatinib versus TKI followed by afatinib). Abbreviations: C→A: afatinib directly after chemotherapy; EGFR, epidermal growth factor receptor; T→A: afatinib on progression with EGFR-TKI; TKI, tyrosine kinase inhibitor.

Figure 5.

Efficacy of sequential EGFR-targeting therapies. (A–D): Efficacy of second treatment line with a reversible EGFR-TKI. (E–H): Efficacy of afatinib as third EGFR-targeting agent (patients still on afatinib treatment were excluded). Abbreviations: EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor.