Efficacy and safety of afatinib in a Chinese population with advanced lung adenocarcinoma with sensitive EGFR mutations

Abstract

Background Afatinib is an irreversible ErbB family blocker that improves progression‐free survival (PFS) of advanced EGFR ‐mutant lung adenocarcinoma compared to chemotherapy. However, afatinib leads to more adverse events than first‐generation EGFR inhibitors. Hence, exploration of the optimal afatinib initial dose and its efficacy and safety in Asian patients has drawn extensive attention. Methods We retrospectively evaluated demographic and clinical information, survival data, and adverse events in advanced non‐small cell lung cancer patients treated with afatinib from 27 February 2017 to 30 October 2018. Results A total of 60 patients were included in the study. Thirty‐nine (65%) patients received afatinib as first‐line treatment. The median PFS was 12.3 months (95% confidence internal 7.6–17.0). Multivariate Cox regression analysis revealed that age, gender, smoking history, baseline brain metastasis status, afatinib starting dose, and mutation type did not significantly influence PFS. No significant difference in median PFS between patients treated with an initial dose of afatinib of 40 mg or 30 mg, either in the first‐line (14.5 vs. 5.2 months; P = 0.101) or in a second or later‐line setting (3.0 vs. 5.0 months; P = 0.375) was observed. The incidence of all grades of rash/acne (92.5% vs. 61.1%; P = 0.011) and paronychia (82.5% vs. 50.0%; P = 0.010) in the 40 mg group was significantly higher than in the 30 mg group. Conclusion First‐line afatinib treatment is beneficial for advanced lung adenocarcinoma patients with sensitive EGFR mutations. Initial dose and baseline brain metastasis status do not significantly impact PFS.

Afatinib treatment response in advanced lung adenocarcinomas harboring uncommon mutations

“…Among them, 14 patients were included in our previous study, and the ORR was reevaluated, and the TTF was reported for the first time. 20 The most common uncommon EGFR mutation was G719X (n = 20; 48%), followed by S768I (n = 12; 29%) and L861Q (n = 3; 7%). Fifteen patients had mutations other than G719X, L861Q, and S768I; seven patients had concomitant common EGFR mutations.…”

“…Among them, 14 patients were included in our previous study, and the ORR was reevaluated, and the TTF was reported for the first time. 20 …”

“…~93% are present in the first four exons (18)(19)(20)(21) of the gene encoding tyrosine kinase domain, including exon 18 Gly719Xaa (G719X) (~3%), exon 21 Leu861Gln (L861Q) (~1%), and exon 20 Ser768Ile (S768I) mutations (~1%), as well as other insertions in exon 19 or 20 (ins19; 0.6%, and ins20; ~6%). 10 Although at low frequency, approximately tens of thousands of new cases worldwide are reported each year because of the large population base of NSCLC.…”

Afatinib as First-Line Treatment in Asian Patients with EGFR Mutation-Positive NSCLC: A Narrative Review of Real-World Evidence

“…As first-line therapy, afatinib was associated with a median PFS of 12.3 months (95% CI 7.6–17.0) in the overall population and 15.6 months (95% CI 9.5–21.8) in patients with the common mutations Del19 or L858R. Median PFS in the first-line setting among patients treated with an initial dose of afatinib 40 mg/day ( n = 29) or 30 mg/day ( n = 10) was 14.5 (95% CI 9.4–19.7) and 5.2 months (95% CI 0.8–9.6), respectively ( p = 0.101), whereas, second- or later-line treatment with afatinib at these starting doses was associated with median PFS of 3.0 ( n = 12, 95% CI 1.3–4.8) and 5.0 ( n = 9, 95% CI 2.5–7.5) months, respectively ( p = 0.375) [ 27 , 38 ]. Similar outcomes were reported in another real-world study in China; in 88 patients who received first-line afatinib, median PFS was 14.2 months [ 39 ].…”

Afatinib for the First-Line Treatment of EGFR Mutation-Positive NSCLC in China: a Review of Clinical Data

“…Real-world data support the findings of prospective studies. While few studies in Chinese patients have been published, a recent analysis of 60 patients treated with afatinib (30% with uncommon EGFR mutations and 40% with baseline brain metastases), showed median PFS of 12.3 months in patients receiving first-line afatinib [36]. A number of other real-world studies conducted in Taiwan also corroborate findings from clinical trials [37][38][39][40]; median PFS with afatinib was around 12 months in NSCLC patients with common EGFR mutations (L858R/Del19), and 11 to almost 20 months in patients with uncommon mutations [39,41].…”