Safety and activity of alectinib plus bevacizumab in patients with advanced ALK-rearranged non-small-cell lung cancer: a phase I/II study

Alectinib, a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is highly effective in advanced ALK-rearranged non-small-cell lung cancer and represents a standard first-line therapy. New strategies are needed, however, to delay resistance. We conducted a phase I/II study to assess the safety and efficacy of combining alectinib with bevacizumab, a monoclonal antibody against vascular endothelial growth factor.
Patients with advanced ALK-rearranged non-squamous non-small-cell lung cancer were enrolled. The phase I portion employed a dose de-escalation strategy with alectinib and bevacizumab starting at the individual standard doses. The primary objective was to determine the recommended phase II dose (RP2D). In phase II, the primary objective was to evaluate the safety of the combination at the RP2D; the secondary objective was to determine extracranial and intracranial efficacy.
Eleven patients were enrolled between September 2015 and February 2020. Mos..... READ ARTICLE

ESMO Open, Cancer Horizons DOI:10.1016/j.esmoop.2021.100342

Authors: J.J. Lin, A. Muzikansky, E. Kennedy, I. Dagogo-Jack, A.T. Shaw, J.F. Gainor

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

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. READ ARTICLE

American Journal of Translational Research DOI:10.1016/j.cllc.2021.06.011

Authors: Huang Z., Xiong Q., Cui Z., Tao H., Zhang S., Wang L., Cui P., Chen S., Huang D., Yang B., Hu Y.

Clinical TrialsKirk SmithMarch 15, 2021crizotinib, bevacizumab, ALK, ROS-1, c-MET, brain metastasis

Lorlatinib and Bevacizumab Activity in ALK- Rearranged Lung Cancers After Lorlatinib Progression

In conclusion, the combination of lorlatinib and bevacizumab demonstrated activity and was safe in patients with heavily pretreated, ALK-rearranged lung cancers that had progressed on single-agent lorlatinib immediately before the combination. These findings add to a growing body of literature on the potential utility of antiangiogenic therapy with TKI therapy in oncogene-driven cancers. READ ARTICLE

JCO Precision Oncology DOI: 10.1200/PO.20.00271

Authors: Choudhury NJ, Young RJ, Sellitti M, Miller A, Drilon A.

Case StudyKirk SmithNovember 1, 2020lorlatinib, bevacizumab

Effect of bevacizumab on brain radiation necrosis in anaplastic lymphoma kinase-positive lung cancer

Central nervous system (CNS) metastases from anaplastic lymphoma kinase (ALK)-positive lung cancer often results in failure of ALK-tyrosine kinase inhibitor (TKI) therapy. Patients with uncontrolled CNS metastases receive radiation therapy, which sometimes causes brain radiation necrosis. We added bevacizumab (15 mg/kg, every 3–4 weeks) to the regimen of four ALK-positive lung cancer patients with brain radiation necrosis who were receiving ALK-TKI therapy. A decrease in brain radiation necrosis was seen in all the patients, and an improvement in symptoms was seen in three patients. In one patient who was receiving corticosteroid therapy, we could taper the dose and subsequently discontinue it. While one patient discontinued bevacizumab because of adverse events, the other three continued with the treatment. Therefore, the combination of bevacizumab with ALK-TKI seems to be an effective, manageable, and tolerable treatment for brain radiation necrosis. READ ARTICLE

Respirology Case Reports DOI:10.1002/rcr2.454

Authors: Kengo Tanigawa, Keiko Mizuno, Yusuke Kamenohara, Taiji Unoki, Shunsuke Misono, Hiromasa Inoue