EGFR-TKI plus bevacizumab versus EGFR-TKI monotherapy for patients with EGFR mutation-positive advanced non-small cell lung cancer-A propensity score matching analysis

Tsai, Jeng Shiuan; Su, Po‐Lan; Yang, Sheng‐An; Chang, Chih-Jen; Lin, Chia Ying; Yen, Yi‐Ting; Tseng, Yau‐Lin; Lai, Wu‐Wei; Lin, Chien Chung; Su, Wu Chou

doi:10.1016/j.jfma.2021.03.023

Cited by 11 publications

(17 citation statements)

References 37 publications

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“…Previous clinical trials involving Japanese EGFR -mutated NSCLC patients demonstrated an add-on of bevacizumab to erlotinib provided a prolonged PFS but not an OS benefit [ 10 , 11 ]. Recently, a similar PFS benefit in patients of EGFR mutation receiving bevacizumab and first-generation EGFR-TKI combination was reported in a real-world study by Tsai et al [ 26 ]. In this study, OS benefit was also observed in the EGFR L858R mutation patients receiving bevacizumab and EGFR-TKI combination.…”

Section: Discussionsupporting

confidence: 65%

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

Kuo

Chiu

Tung

et al. 2022

Cancers

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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.

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Section: Discussionsupporting

confidence: 65%

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

Kuo

Chiu

Tung

et al. 2022

Cancers

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“…In the post-hoc analysis, cohort of EGFR exon 19 deletion patients was the major source that contributed to the OS benefit whereas cohort of EGFR L858R patients generally received minimal treatment benefit from osimertinib. In contrary, the post-hoc analysis of NEJ 026 study revealed that bevacizumab likely offered additional benefit to the cohort of EGFR L858R patients and this finding has also been reported in real-world patients 32 . The present study also observed a trend of OS benefit in EGFR L858R patients who received combination of EGFR-TKI and bevacizumab.…”

Section: Discussionmentioning

confidence: 87%

The different overall survival between single-agent EGFR-TKI treatment and with bevacizumab in non-small cell lung cancer patients with brain metastasis

Chiu

Tung

Huang

et al. 2022

Sci Rep

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Comparison of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) monotherapy or with bevacizumab in real-world non-small cell lung cancer (NSCLC) patients was lacking. 310 patients of advanced NSCLC with common EGFR mutation receiving first-generation EGFR-TKI monotherapy or with bevacizumab were included and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutation were analysed. Patients receiving EGFR-TKI and bevacizumab were significantly younger, had better performance status and with high incidence of brain metastasis (55.8%). In the propensity-score matched cohort, PFS (13.5 vs. 13.7 months; log-rank p = 0.700) was similar between the two groups. The OS (61.3 vs. 34.2 months; log-rank p = 0.010) and risk reduction of death (HR 0.42 [95% CI 0.20–0.85]; p = 0.017) were significantly improved in EGFR-TKI plus bevacizumab group. Analysis of treatment by brain metastasis status demonstrated EGFR-TKI plus bevacizumab in patients with brain metastasis was associated with significant OS benefit compared to other groups (log-rank p = 0.030) and these patients had lower early-CNS and early-systemic progressions. The secondary T790M did not significantly differ between EGFR-TKI plus bevacizumab and EGFR-TKI monotherapy groups (66.7% vs. 75.0%, p = 0.460). Forty-one (31.1%) and 31 (23.5%) patients received subsequent osimertinib and chemotherapy, respectively. The post-progression OS of osimertinib and chemotherapy were 22.1 and 44.9 months in EGFR-TKI plus bevacizumab group and were 10.0 and 14.1 months in EGFR-TKI monotherpay group, respectively. First-generation EGFR-TKI with bevacizumab improved treatment efficacy in real-world patients of NSCLC with EGFR mutation. Patients with brain metastasis received additional OS benefit from this treatment.

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“…The median PFS was 22.0 months (95% CI, 19.7 to 22.33), and the median OS 47.6 months (95% CI, 38.87 to 56.37). In another real-world, two-arm study, Tsai et al [ 21 ] demonstrated that the combination of EGFR-TKI and bevacizumab improved PFS when compared to the monotherapy group (17.0 months vs. 11.0 months; HR, 0.48; p=0.002) for patients with EGFR mutation-positive advanced NSCLC. In our research, the ORR was 77.8%, and the DCR 94.4% in advanced EGFR -mutant lung adenocarcinoma patients receiving EGFR-TKI plus bevacizumab.…”

Section: Discussionmentioning

confidence: 99%

“…In the RELAY study, the HRs of PFS in the L858R mutation and exon 19 deletion groups were 0.618 and 0.651, respectively [ 16 ]. In a real-world analysis, Tsai et al [ 21 ] suggested that the combination of EGFR-TKI and bevacizumab could significantly improve PFS and OS in NSCLC patients harboring L858R mutation group; however, the subgroup analysis found that there was no clinical efficacy in patients with exon 19 deletion. In our research, there was no statistical difference in the median PFS of EGFR-TKIs plus bevacizumab between patients with exon 19 deletion and L858R mutation (17.1 months vs. 16.2 months; log-rank test, p=0.311).…”

Section: Discussionmentioning

confidence: 99%

“…Although there have been some real-world analyses of the efficacy of EGFR-TKIs plus bevacizumab [ 19 – 21 ], few studies have addressed the impact of different first-line EGFR-TKIs with bevacizumab on the clinical outcomes of combination therapy. Therefore, we conducted the present study in order to investigate the issues mentioned above.…”

Section: Introductionmentioning

confidence: 99%

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The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

et al. 2022

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The aim of this study was to investigate the efficacy of various Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitors (TKIs) plus bevacizumab in advanced EGFRmutant lung adenocarcinoma patients. Materials and MethodsFrom August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. ResultsA total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). ConclusionOur research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib CANCER RESEARCH AND TREATMENT (CRT) 4

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EGFR-TKI plus bevacizumab versus EGFR-TKI monotherapy for patients with EGFR mutation-positive advanced non-small cell lung cancer-A propensity score matching analysis

Cited by 11 publications

References 37 publications

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

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

The different overall survival between single-agent EGFR-TKI treatment and with bevacizumab in non-small cell lung cancer patients with brain metastasis

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

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