Survival of chemo-naïve patients with EGFR mutation-positive advanced non-small cell lung cancer after treatment with afatinib and bevacizumab: updates from the Okayama Lung Cancer Study Group Trial 1404

Abstract

Background In a phase I study, afatinib (30 mg/body daily) plus bevacizumab (15 mg/kg every 3 weeks) was well tolerated and showed favourable outcomes in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer. Herein, we report the 2-year progression-free survival, overall survival and safety profile of these patients. Methods Chemo-naïve patients with EGFR-mutant advanced non-small-cell lung cancer were enrolled. One group of patients received 40 mg afatinib daily and 15 mg/kg bevacizumab every 3 weeks (level 0) until disease progression or severe toxicity. Another group of patients received 30 mg afatinib daily and the same dose of bevacizumab (level 1). Dose-limiting toxicity was the primary endpoint, whereas long-term progression-free survival, overall survival and tolerability were secondary endpoints. Survival rates were estimated using the Kaplan–Meier method. Results The study included 19 patients (level 0: 5; level − 1: 14). Until the data cut-off date, seven patients continued the treatment, whereas 12 discontinued due to disease progression (n = 5) or toxicity (n = 7). The median PFS was 24.2 months, while the median overall survival was not reached. All patients developed adverse effects. Diarrhoea and skin rash were frequently observed as severe adverse events (grade 3). A secondary EGFR mutation (T790M) was detected in two patients after progression. Conclusions Prolonged follow-up revealed that combination therapy with afatinib and bevacizumab might improve survival outcomes in EGFR-mutant advanced non-small-cell lung cancer patients and seems to be promising. Trial registration UMIN000015944.

Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study

“… 13 – 16 A phase I clinical trial, the Okayama Lung Cancer Study Group Trial 1404, reported that the combination of afatinib and bevacizumab therapy was feasible and safe for the treatment of chemo-naïve advanced EGFR-mutated NSCLC patients. 17 In the same trial, afatinib combined with bevacizumab showed 24.2 months of PFS in chemo-naïve advanced EGFR-mutated NSCLC patients. 17 Another previous retrospective study showed that the combination of afatinib and bevacizumab had an 87.7% ORR and 23.9 months PFS as first-line therapy in advanced EGFR-mutated lung adenocarcinoma patients.…”

“… 17 In the same trial, afatinib combined with bevacizumab showed 24.2 months of PFS in chemo-naïve advanced EGFR-mutated NSCLC patients. 17 Another previous retrospective study showed that the combination of afatinib and bevacizumab had an 87.7% ORR and 23.9 months PFS as first-line therapy in advanced EGFR-mutated lung adenocarcinoma patients. 18 …”

“…17 In the same trial, afatinib combined with bevacizumab showed 24.2 months of PFS in chemo-naïve advanced EGFR-mutated NSCLC patients. 17 Another previous retrospective study showed that the combination of afatinib and bevacizumab had an 87.7% ORR and 23.9 months PFS as first-line therapy in advanced EGFRmutated lung adenocarcinoma patients. 18 Although previous clinical studies demonstrated that bevacizumab combined with afatinib or erlotinib was an effective treatment for advanced EGFR-mutated NSCLC, few studies have investigated the comparison between afatinib and erlotinib combined with bevacizumab in untreated advanced EGFR-mutated lung adenocarcinoma patients.…”

Afatinib Treatment Alone or with Bevacizumab in a Real-World Cohort of Non-Small Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Mutation

“…Many attempts have been made to investigate the combination of afatinib with bevacizumab for the first-line treatment of EGFR -mutated NSCLC. A manageable adverse event and a promising efficacy were observed in some early-phase clinical trials [ 18 , 19 ] and a satisfactory tolerability and treatment outcome were also reported in real-world patients [ 20 ]. Nevertheless, whether the combination of afatinib and bevacizumab presents a synergistic effect and, thus, outperforms the single-agent afatinib in a front-line setting, remains largely unknown.…”

Afatinib 30 mg in the treatment of common and uncommon EGFR-mutated advanced lung adenocarcinomas: a retrospective, single-center, longitudinal study

“…Recent studies demonstrated that afatinib at 30 mg/d was more tolerable than the dose of 40 mg/d, but favorable efficacy was maintained for Asian patients with NSCLC (18)(19)(20). However, evidence is sparse regarding the efficacy and safety of afatinib at 30 mg in the treatment of advanced LAD with uncommon EGFR mutations.…”