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Journal of Cancer Research and Clinical Oncology

Erschienen in:

15.07.2023 | Research

Outcome benefits of bevacizumab biosimilar (SIBP04) combined with carboplatin and paclitaxel in advanced non-squamous non-small-cell lung cancer patients with EGFR mutation: subgroup analysis of a prospective, randomized phase III clinical trial

verfasst von: Aidong Qu, Shiying Zhang, Hongxia Zou, Sixiu Li, Dandan Chen, Yaowen Zhang, Songsong Li, Huijun Zhang, Ji Yang, Yunkai Yang, Yubao Huang, Xiuling Li, Yuntao Zhang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 14/2023

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Abstract

Purpose

SIBP04 is a bevacizumab biosimilar, and bevacizumab combined with carboplatin and paclitaxel in advanced non-squamous non-small-cell lung cancer (nsqNSCLC) has been recommended as the first-line treatment choice. However, the efforts of bevacizumab combined with carboplatin and paclitaxel for nsqNSCLC patients with EGFR mutation remained unclear. Here we report an EGFR mutation subgroup analysis of a prospective, randomized phase III clinical trial (NCT05318443).

Methods

In this randomized, double-blind, multi-center, parallel controlled, phase III clinical trial, locally advanced, metastatic NSCLC patients were enrolled, and EGFR expression was examined and considered as a stratification factor. All patients received 4 to 6 cycles of paclitaxel and carboplatin plus SIBP04 or bevacizumab 15 mg/kg intravenously followed by SIBP04 15 mg/kg maintenance until intolerable toxicity, disease progression or death. Patients with EGFR mutation and wild-type were assessed for progression-free survival (PFS) and overall survival (OS).

Results

EGFR expression was examined in 398 NSCLC patients (142 with EGFR mutation, 256 with EGFR wild type). PFS in EGFR mutation patients was significantly longer than EGFR wild-type patients (10.91 vs. 7.82 months; HR = 0.692, 95% CI 0.519–0.921, P = 0.011). The median OS in patients with EGFR mutation was not reached while that of EGFR wild-type group was 17.54 months (HR = 0.398, 95% CI 0.275–0.575, P < 0.001). However, there were no significant differences in objective response rate (61.97% vs. 55.86%, P = 0.237) or disease control rate (90.14% vs. 89.84%, P = 0.925).

Conclusion

Bevacizumab combined with chemotherapy significantly prolonged the PFS and OS of advanced nsqNSCLC patients with EGFR mutation.

Ascha MS et al (2019) Bevacizumab for the treatment of non-small cell lung cancer patients with synchronous brain metastases. Sci Rep 9:17792. https://doi.org/10.1038/s41598-019-54513-3CrossRefPubMedPubMedCentral

Bar J et al (2021) Long-term survival of patients with metastatic non-small-cell lung cancer over five decades. J Oncol 2021:7836264. https://doi.org/10.1155/2021/7836264CrossRefPubMedPubMedCentral

Bethune G et al (2010) Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis 2:48–51PubMedPubMedCentral

Ciardiello F et al (2001) Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin Cancer Res 7:1459–1465PubMed

Crino L et al (2010) Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study. Lancet Oncol 11:733–740. https://doi.org/10.1016/S1470-2045(10)70151-0CrossRefPubMed

da Cunha SG et al (2011) EGFR mutations and lung cancer. Annu Rev Pathol 6:49–69. https://doi.org/10.1146/annurev-pathol-011110-130206CrossRef

Domvri K et al (2013) Molecular targeted drugs and biomarkers in NSCLC, the evolving role of individualized therapy. J Cancer 4:736–754. https://doi.org/10.7150/jca.7734CrossRefPubMedPubMedCentral

Ferrara N (2005) VEGF as a therapeutic target in cancer. Oncology 69(Suppl 3):11–16. https://doi.org/10.1159/000088479CrossRefPubMed

Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974. https://doi.org/10.1038/nature04483CrossRefPubMed

Gazdar AF (2009) Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 28(Suppl 1):S24-31. https://doi.org/10.1038/onc.2009.198CrossRefPubMedPubMedCentral

Goel S et al (2011) Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 91:1071–1121. https://doi.org/10.1152/physrev.00038.2010CrossRefPubMed

Larsen AK et al (2011) Targeting EGFR and VEGF(R) pathway cross-talk in tumor survival and angiogenesis. Pharmacol Ther 131:80–90. https://doi.org/10.1016/j.pharmthera.2011.03.012CrossRefPubMed

Lichtenberger BM et al (2010) Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell 140:268–279. https://doi.org/10.1016/j.cell.2009.12.046CrossRefPubMed

Mok TS et al (2011) 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 7(Suppl 2):4–12. https://doi.org/10.1111/j.1743-7563.2011.01397.xCrossRefPubMed

Pao W, Chmielecki J (2010) Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat Rev Cancer 10:760–774. https://doi.org/10.1038/nrc2947CrossRefPubMedPubMedCentral

Peng XH et al (2006) Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem 281:25903–25914. https://doi.org/10.1074/jbc.M603414200CrossRefPubMed

Presta LG et al (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593–4599PubMed

Puri N, Salgia R (2008) Synergism of EGFR and c-Met pathways, cross-talk and inhibition, in non-small cell lung cancer. J Carcinog 7:9. https://doi.org/10.4103/1477-3163.44372CrossRefPubMedPubMedCentral

Reck M et al (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27:1227–1234. https://doi.org/10.1200/JCO.2007.14.5466CrossRefPubMed

Regad T (2015) Targeting RTK signaling pathways in cancer. Cancers (basel) 7:1758–1784. https://doi.org/10.3390/cancers7030860CrossRefPubMedPubMedCentral

Rosell R et al (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361:958–967. https://doi.org/10.1056/NEJMoa0904554CrossRefPubMed

Sandler A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550. https://doi.org/10.1056/NEJMoa061884CrossRefPubMed

Sharma SV et al (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7:169–181. https://doi.org/10.1038/nrc2088CrossRefPubMed

Shigematsu H et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 97:339–346. https://doi.org/10.1093/jnci/dji055CrossRefPubMed

Siegel RL et al (2023) Cancer statistics, 2023. CA Cancer J Clin 73:17–48. https://doi.org/10.3322/caac.21763CrossRefPubMed

Sung H et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660CrossRefPubMed

Tanaka I et al (2020) Potential benefits of bevacizumab combined with platinum-based chemotherapy in advanced non-small-cell lung cancer patients with EGFR mutation. Clin Lung Cancer 21:273-280e274. https://doi.org/10.1016/j.cllc.2020.01.011CrossRefPubMed

Tsai CM et al (2011) Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study. J Thorac Oncol 6:1092–1097. https://doi.org/10.1097/JTO.0b013e318216687dCrossRefPubMed

Xu L et al (2010) Epidermal growth factor receptor regulates MET levels and invasiveness through hypoxia-inducible factor-1alpha in non-small cell lung cancer cells. Oncogene 29:2616–2627. https://doi.org/10.1038/onc.2010.16CrossRefPubMedPubMedCentral

Zhou CC et al (2014) Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study. Clin Transl Oncol 16:463–468. https://doi.org/10.1007/s12094-013-1102-5CrossRefPubMed

Zhou C et al (2015) BEYOND: a randomized, double-blind, placebo-controlled, multicenter, phase III study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer. J Clin Oncol 33:2197–2204. https://doi.org/10.1200/JCO.2014.59.4424CrossRefPubMed

Titel: Outcome benefits of bevacizumab biosimilar (SIBP04) combined with carboplatin and paclitaxel in advanced non-squamous non-small-cell lung cancer patients with EGFR mutation: subgroup analysis of a prospective, randomized phase III clinical trial
verfasst von: Aidong Qu
Shiying Zhang
Hongxia Zou
Sixiu Li
Dandan Chen
Yaowen Zhang
Songsong Li
Huijun Zhang
Ji Yang
Yunkai Yang
Yubao Huang
Xiuling Li
Yuntao Zhang
Publikationsdatum: 15.07.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 14/2023
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-023-05103-4

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Outcome benefits of bevacizumab biosimilar (SIBP04) combined with carboplatin and paclitaxel in advanced non-squamous non-small-cell lung cancer patients with EGFR mutation: subgroup analysis of a prospective, randomized phase III clinical trial