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

Abstract

Background: Treatment outcome between afatinib alone or with bevacizumab in non-small cell lung cancer (NSCLC) patient with epidermal growth factor receptor (EGFR) mutation remains insufficiently reported. Methods: A total of 405 advanced NSCLC patients with sensitizing-EGFR mutation receiving first-line single-agent afatinib or with bevacizumab were grouped and propensity score-matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutation were analyzed. Results: In the original cohort, 367 (90.6%) patients received afatinib treatment alone and 38 (9.4%) patients received afatinib plus bevacizumab. Patients who received bevacizumab combination were significantly younger (54.6 ± 10.9 vs. 63.9 ± 11.5; p < 0.001) compared to the afatinib alone group. After propensity score matching, the afatinib alone and afatinib plus bevacizumab groups contained 118 and 34 patients, respectively. A non-significantly higher objective response was noted in the afatinib plus bevacizumab group (82.4% vs. 67.8%; p = 0.133). In the propensity score-matched cohort, a bevacizumab add-on offered no increased PFS (16.1 vs. 15.0 months; p = 0.500), risk reduction of progression (HR 0.85 [95% CI, 0.52–1.40]; p = 0.528), OS benefit (32.1 vs. 42.0 months; p = 0.700), nor risk reduction of death (HR 0.85 [95% CI, 0.42–1.74] p = 0.660) compared to the single-agent afatinib. The secondary T790M rate in afatinib plus bevacizumab and afatinib alone groups was similar (56.3% vs. 49.4%, p = 0.794). Multivariate analysis demonstrated that EGFR L858R (OR 0.51 [95% CI, 0.26–0.97]; p = 0.044), EGFR uncommon mutation (OR 0.14 [95% CI, 0.02–0.64]; p = 0.021), and PFS longer than 12 months (OR 2.71 [95% CI, 1.39–5.41]; p = 0.004) were independent predictors of secondary T790M positivity. Conclusion: Bevacizumab treatment showed moderate efficacy in real-world, afatinib-treated NSCLC patients with EGFR-sensitizing mutation.

Factors associated with prolonged progression‐free survival of patients treated with first‐line afatinib for advanced epidermal growth factor receptor‐mutated non‐small cell lung cancer

“…Previous prospective clinical trials showed that erlotinib combined with bevacizumab significantly prolonged PFS compared to erlotinib alone but had no significant effects on OS 23–25 . Our recent real‐world cohort studies showed that patients receiving only afatinib treatment had a median PFS (16.1 months vs. 15.0 months; p = 0.500) and median OS (32.1 months vs. 42.0 months; p = 0.700) similar to those of patients receiving afatinib plus bevacizumab 26 . Afatinib combined with bevacizumab was equally as effective as erlotinib combined with bevacizumab in terms of the objective response rate, disease control rate, median PFS, and median OS 27 .…”

“… 23 , 24 , 25 Our recent real‐world cohort studies showed that patients receiving only afatinib treatment had a median PFS (16.1 months vs. 15.0 months; p = 0.500) and median OS (32.1 months vs. 42.0 months; p = 0.700) similar to those of patients receiving afatinib plus bevacizumab. 26 Afatinib combined with bevacizumab was equally as effective as erlotinib combined with bevacizumab in terms of the objective response rate, disease control rate, median PFS, and median OS. 27 In the present study, median PFS and median OS did not differ significantly between patients receiving the afatinib and bevacizumab combination and those receiving afatinib only (13.8 vs. 14.5 months [ p = 0.782] and 37.5 vs. 26.3 months [ p = 0.052], respectively).…”

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

“…A multicenter observational study reported that the first-line afatinib plus bevacizumab demonstrated an ORR of 87.7%, a median PFS of 23.9 months, and a median OS of 45.9 months. Further prospective studies are warranted to confirm the clinical efficacy [37,38]. In addition, immunotherapy plus chemotherapy tended to be more effective than immunotherapy alone in previously TKI-treated NSCLC harboring EGFR mutations [39].…”

“…In a retrospective study, alternative treatment with Chinese herbal medicine (CHM) during first-line EGFR-TKI showed a tolerable toxicity profile and a tendency toward better progression-free sur-vival (PFS)and overall survival (OS) than those who did not receive CHM [35]. Multiple studies have reported that not only erlotinib plus bevacizumab, but also afatinib combined with bevacizumab, demonstrated favorable efficacy for the first-line treatment of advanced pulmonary adenocarcinoma harboring EGFR mutations [36][37][38]. A multicenter observational study reported that the first-line afatinib plus bevacizumab demonstrated an ORR of 87.7%, a median PFS of 23.9 months, and a median OS of 45.9 months.…”

Clinical advances in EGFR-TKI combination therapy for EGFR-mutated NSCLC: a narrative review

“…ARTEMIS-CTONG1509, a multicenter phase-III study, found that bevacizumab (an anti-VEGF antibody) plus erlotinib significantly improved PFS in patients with EGFR-mutated NSCLC, including those with brain metastases at the baseline ( 119 ). Kuo et al found that a bevacizumab combination treatment showed moderate efficacy in afatinib-treated NSCLC patients with the EGFR-sensitizing mutation ( 120 ). However, a treatment of osimertinib plus bevacizumab failed to show any efficacy in improving the PFS of EGFR-mutated NSCLC patients, with similar findings reported in the studies of Soo et al and Kenmotsu et al ( 121 , 122 ).…”