Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 15;13(3):1526-1534.
eCollection 2021.

Efficacy and safety of crizotinib plus bevacizumab in ALK/ROS-1/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study

Ziwei Huang  1   2 , Qi Xiong  2 , Zhi Cui  2 , Haitao Tao  2 , Sujie Zhang  2 , Lijie Wang  2 , Pengfei Cui  2 , Shixue Chen  2 , Di Huang  1 , Bo Yang  2 , Yi Hu  1   2
Affiliations

Efficacy and safety of crizotinib plus bevacizumab in ALK/ROS-1/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study

Ziwei Huang et al. Am J Transl Res. .

Abstract

Background: Crizotinib is a tyrosine kinase inhibitor (TKI) effective in ALK/ROS-1/c-MET positive non-small cell lung cancer (NSCLC) patients. Bevacizumab is an antiangiogenic monoclonal antibody, and improves clinical benefit of NSCLC in combination with EGFR-TKIs or chemotherapy. However, the efficacy and safety of crizotinib plus bevacizumab in treating naive ALK/ROS-1/c-MET positive NSCLC patients have not been studied.

Methods: In this open-label, single-arm, prospective observational study, locally advanced or metastatic ALK rearrangement/ROS-1 fusion/c-MET amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death. Primary end point was progressive free survival (PFS), secondary end points were duration of response (DOR), overall response rate (ORR), disease control rate (DCR) and safety. Patients receiving ≥1 cycle of treatment were evaluated.

Findings: Fourteen patients were eligible for analyzing between June 2016 and October 2017. There were 12 patients with ALK rearrangement, 1 patient with ROS-1 fusion, and 1 patient with c-MET amplification. The median follow-up time was 42.8 months. The median PFS and DOR of the patients with ALK rearrangement were 13.9 and 14.8 months respectively. Of the 12 patients, 7 gained partial response, 5 gained stable disease. The ORR and DCR were 58.3% and 100%. The PFS were 12.9 months and 1.9 months for patient with ROS-1 fusion or c-MET amplification. The most two common treatment-related adverse events were fatigue (28.6%) and rash (21.4%). 3 patients discontinued therapy because of liver damage or hemoptysis.

Interpretation: This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive ALK rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ROS-1/c-MET positive NSCLC patients.

Keywords: ALK; Crizotinib; ROS-1; bevacizumab; brain metastasis; c-MET.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
A. The typical IHC image of the ALK (Ventana) (+) patient; B. The IHC image of the c-MET (+++); C. The FISH image of the ROS-1 (+).
Figure 2
Figure 2
The median PFS of 12 ALK positive patients was 13.9 months.
Figure 3
Figure 3
The median DOR of 12 ALK positive patients was 14.8 months.
Figure 4
Figure 4
The OS was not reached. The 1-year-survival rate and 3-year-survial rate were 90.9% and 79.5%.
Figure 5
Figure 5
Best percentage change from baseline in tumor volume after treatment. *indicated the c-MET (+) patient and #indicated the ROS-1 (+) patient.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, Chirieac LR, D’Amico TA, Demmy TL, Ganti AK, Govindan R, Grannis FW Jr, Jahan T, Jahanzeb M, Johnson DH, Kessinger A, Komaki R, Kong FM, Kris MG, Krug LM, Le QT, Lennes IT, Martins R, O’Malley J, Osarogiagbon RU, Otterson GA, Patel JD, Pisters KM, Reckamp K, Riely GJ, Rohren E, Simon GR, Swanson SJ, Wood DE, Yang SC Members NN-SCLCP. Non-small cell lung cancer. J Natl Compr Canc Netw. 2010;8:740–801. - PubMed
    1. Sequist LV, Heist RS, Shaw AT, Fidias P, Rosovsky R, Temel JS, Lennes IT, Digumarthy S, Waltman BA, Bast E, Tammireddy S, Morrissey L, Muzikansky A, Goldberg SB, Gainor J, Channick CL, Wain JC, Gaissert H, Donahue DM, Muniappan A, Wright C, Willers H, Mathisen DJ, Choi NC, Baselga J, Lynch TJ, Ellisen LW, Mino-Kenudson M, Lanuti M, Borger DR, Iafrate AJ, Engelman JA, Dias-Santagata D. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol. 2011;22:2616–2624. - PMC - PubMed
    1. Choi YL, Takeuchi K, Soda M, Inamura K, Togashi Y, Hatano S, Enomoto M, Hamada T, Haruta H, Watanabe H, Kurashina K, Hatanaka H, Ueno T, Takada S, Yamashita Y, Sugiyama Y, Ishikawa Y, Mano H. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res. 2008;68:4971–4976. - PubMed
    1. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007;131:1190–1203. - PubMed
    1. Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012;18:378–381. - PubMed

LinkOut - more resources