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

Overview

Journal Ther Adv Med Oncol

Specialty Oncology

Date 2022 Jul 28

PMID 35898964

Authors

Suey-Haur Lee

Yu-Ching Lin

Li-Chung Chiu

Jia-Shiuan Ju

Pi-Hung Tung

Allen Chung-Cheng Huang

Shih-Hong Li

Yueh-Fu Fang

Chih-Hung Chen

Scott Chih-Hsi Kuo

Chin-Chou Wang

Cheng-Ta Yang

Ping-Chih Hsu

Affiliations

Soon will be listed here.

Abstract

Background: Although bevacizumab in combination with afatinib or erlotinib is an effective and safe first-line therapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), there are very few clinical data comparing afatinib and erlotinib combined with bevacizumab. We performed a retrospective multicenter analysis for the comparison of two combination therapies.

Methods: Between May 2015 and October 2020, data of 135 stage IIIB/IV EGFR-mutated NSCLC patients receiving first-line afatinib or erlotinib combined with bevacizumab combination therapy in Linkou, Keelung, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals were retrieved and retrospectively analyzed.

Results: In all, 67 patients received afatinib plus bevacizumab, and 68 patients received erlotinib plus bevacizumab. Afatinib combined with bevacizumab had an objective response rate (ORR) of 82.1% and a disease control rate (DCR) of 97.0%, and the ORR and DCR were 83.8 and 95.6%, respectively, in the erlotinib combined with bevacizumab group ( = 0.798 and = 1.000). The median progression-free survival was 20.7 and 20.3 months for the afatinib plus bevacizumab group and the erlotinib plus bevacizumab group, respectively [hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.891-1.953; = 0.167). The overall survival was 41.9 and 51.0 months for the afatinib plus bevacizumab group and erlotinib plus bevacizumab group, respectively (HR = 1.42; 95% CI, 0.829-2.436; = 0.201). The secondary EGFR-T790M mutation rates after disease progression were 44% in the afatinib plus bevacizumab group and 58.8% in the erlotinib plus bevacizumab group ( = 0.165). Skin toxicity was the most frequent treatment-related adverse event (AE) in both treatment groups. Diarrhea, an AE, occurred significantly more frequently in the afatinib plus bevacizumab group than in the erlotinib plus bevacizumab group ( < 0.05).

Conclusion: Afatinib combined with bevacizumab was equally as effective as erlotinib combined with bevacizumab for untreated advanced EGFR-mutated NSCLC. Prospective clinical studies that explore bevacizumab combined with afatinib or erlotinib for advanced EGFR-mutated NSCLC are warranted.

Citing Articles

Clinical outcome analysis of different first‑ and second‑generation EGFR‑tyrosine kinase inhibitors in untreated patients with EGFR‑mutated non‑small cell lung cancer with baseline brain metastasis.

Hsu C, Chiu L, Ko H, Wu C, Kuo S, Ju J Oncol Lett. 2025; 29(4):201.

PMID: 40070793 PMC: 11894514. DOI: 10.3892/ol.2025.14947.

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.

Chiu L, Hsu P, Wang C, Ko H, Kuo S, Ju J Thorac Cancer. 2024; 15(7):529-537.

PMID: 38279515 PMC: 10912535. DOI: 10.1111/1759-7714.15212.

Sequential treatment in advanced epidermal growth factor receptor-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with 1st/2nd-generation EGFR-tyrosine kinase inhibitors.

Hsu P, Huang C, Lin Y, Lee S, Chiu L, Wu C Front Oncol. 2023; 13:1249106.

PMID: 37854677 PMC: 10579797. DOI: 10.3389/fonc.2023.1249106.

Clinical outcome analysis of non-small cell lung cancer patients with brain metastasis receiving metastatic brain tumor resection surgery: a multicenter observational study.

Hsu P, Chiu L, Chen K, Wang C, Wu C, Wu C Am J Cancer Res. 2023; 13(8):3607-3617.

PMID: 37693127 PMC: 10492134.

Bevacizumab-Induced Thrombotic Microangiopathy (TMA) in Metastatic Lung Adenocarcinoma Patients Receiving Nivolumab Combined with Bevacizumab, Carboplatin and Paclitaxel: Two Case Reports.

Hsu P, Chen T, Tsai T, Yang C Clin Pract. 2023; 13(1):200-205.

PMID: 36826160 PMC: 9955069. DOI: 10.3390/clinpract13010018.

References

Hsu P, Huang C, Wang C, Kuo S, Chu C, Tung P . The Combination of Afatinib and Bevacizumab in Untreated EGFR-Mutated Advanced Lung Adenocarcinoma: A Multicenter Observational Study. Pharmaceuticals (Basel). 2020; 13(11). PMC: 7690705. DOI: 10.3390/ph13110331. View

Wang M, Herbst R, Boshoff C . Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med. 2021; 27(8):1345-1356. DOI: 10.1038/s41591-021-01450-2. View

Wu S, Shi X, Si X, Liu Y, Lu T, Zhang L . EGFR T790M detection in formalin-fixed paraffin-embedded tissues of patients with lung cancer using RNA-based in situ hybridization: A preliminary feasibility study. Thorac Cancer. 2019; 10(10):1936-1944. PMC: 6775006. DOI: 10.1111/1759-7714.13169. View

Feng P, Chen K, Huang Y, Luo C, Wu S, Chen T . Bevacizumab Reduces S100A9-Positive MDSCs Linked to Intracranial Control in Patients with EGFR-Mutant Lung Adenocarcinoma. J Thorac Oncol. 2018; 13(7):958-967. DOI: 10.1016/j.jtho.2018.03.032. View

Park K, Tan E, OByrne K, Zhang L, Boyer M, Mok T . Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016; 17(5):577-89. DOI: 10.1016/S1470-2045(16)30033-X. View

Zhou C, Wu Y, Chen G, Feng J, Liu X, Wang C . Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015; 26(9):1877-1883. DOI: 10.1093/annonc/mdv276. View

Mok T, Hsia T, Tsai C, Tsang K, Chang G, Chang J . Efficacy of bevacizumab with cisplatin and gemcitabine in Asian patients with advanced or recurrent non-squamous non-small cell lung cancer who have not received prior chemotherapy: a substudy of the Avastin in Lung trial. Asia Pac J Clin Oncol. 2011; 7 Suppl 2:4-12. DOI: 10.1111/j.1743-7563.2011.01397.x. View

Huang Y, Hsu K, Chin C, Tseng J, Yang T, Chen K . The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma. Cancer Res Treat. 2021; 54(2):434-444. PMC: 9016311. DOI: 10.4143/crt.2021.671. View

Akamatsu H, Toi Y, Hayashi H, Fujimoto D, Tachihara M, Furuya N . Efficacy of Osimertinib Plus Bevacizumab vs Osimertinib in Patients With EGFR T790M-Mutated Non-Small Cell Lung Cancer Previously Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor: West Japan Oncology Group 8715L Phase 2.... JAMA Oncol. 2021; 7(3):386-394. PMC: 7791398. DOI: 10.1001/jamaoncol.2020.6758. View

10.

Rosell R, Dafni U, Felip E, Curioni-Fontecedro A, Gautschi O, Peters S . Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial. Lancet Respir Med. 2017; 5(5):435-444. DOI: 10.1016/S2213-2600(17)30129-7. View

11.

Paz-Ares L, Soulieres D, Moecks J, Bara I, Mok T, Klughammer B . Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC. J Cell Mol Med. 2014; 18(8):1519-39. PMC: 4190899. DOI: 10.1111/jcmm.12278. View

12.

Hsu P, Wang C, Kuo S, Lin S, Lo Y, Huang A . The Co-Expression of Programmed Death-Ligand 1 (PD-L1) in Untreated EGFR-Mutated Metastatic Lung Adenocarcinoma. Biomedicines. 2020; 8(2). PMC: 7167989. DOI: 10.3390/biomedicines8020036. View

13.

Soo R, Han J, Dafni U, Cho B, Yeo C, Nadal E . A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER.... Ann Oncol. 2021; 33(2):181-192. DOI: 10.1016/j.annonc.2021.11.010. View

14.

Oxnard G, Hu Y, Mileham K, Husain H, Costa D, Tracy P . Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol. 2018; 4(11):1527-1534. PMC: 6240476. DOI: 10.1001/jamaoncol.2018.2969. View

15.

Aix S, Novello S, Garon E, Nakagawa K, Nadal E, Moro-Sibilot D . RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis. Cancer Treat Res Commun. 2021; 27:100378. DOI: 10.1016/j.ctarc.2021.100378. View

16.

Ninomiya T, Ishikawa N, Inoue K, Kubo T, Yasugi M, Shibayama T . Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol. Clin Lung Cancer. 2018; 20(2):134-138. DOI: 10.1016/j.cllc.2018.10.008. View

17.

Li K, Yang M, Liang N, Li S . Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution (Review). Oncol Rep. 2017; 37(3):1347-1358. PMC: 5364853. DOI: 10.3892/or.2017.5409. View

18.

Ahn M, Tsai C, Hsia T, Wright E, Chang J, Kim H . Cost-effectiveness of bevacizumab-based therapy versus cisplatin plus pemetrexed for the first-line treatment of advanced non-squamous NSCLC in Korea and Taiwan. Asia Pac J Clin Oncol. 2011; 7 Suppl 2:22-33. DOI: 10.1111/j.1743-7563.2011.01399.x. View

19.

Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V . Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol. 2010; 21(9):1804-1809. PMC: 2924992. DOI: 10.1093/annonc/mdq020. View

20.

Ramalingam S, Vansteenkiste J, Planchard D, Cho B, Gray J, Ohe Y . Overall Survival with Osimertinib in Untreated, -Mutated Advanced NSCLC. N Engl J Med. 2019; 382(1):41-50. DOI: 10.1056/NEJMoa1913662. View