Alberto A. Chiappori, MD
Researchers are exploring VEGF and EGFR inhibitors in combination with other therapies for patients with non–small cell lung cancer (NSCLC) in hopes of maximizing clinical outcomes while keeping toxicity levels low.
An ongoing phase I study is investigating the VEGFR2 inhibitor ramucirumab (Cyramza) versus the EGFR inhibitor necitumumab (Portrazza), both in combination with the EGFR inhibitor osimertinib (Tagrisso) in patients with advanced, T790M
-mutant NSCLC who progress on treatment with an EGFR tyrosine kinase inhibitor (NCT02789345).
The VEGF inhibitor bevacizumab (Avastin) is being studied across several settings and in combination with various regimens. For example, the angiogenesis inhibitor is being studied in combination with carboplatin/gemcitabine beyond progression in patients with locally advanced/metastatic NSCLC who have not received prior systemic therapy in a phase II trial (NCT00702975).
In an interview during the 2016 OncLive
State of the Science Summit on Advanced Non–Small Cell Lung Cancer, Alberto A. Chiappori, MD, a senior member in the Department of Thoracic Oncology at Moffitt Cancer Center, spoke on monoclonal antibodies targeting VEGF and EGFR, their benefits and limitations, and how he sees the field evolving.
OncLive: At this meeting, you discussed antibodies targeting angiogenesis and EGFR. What is important to share in this area?
: I presented information regarding monoclonal antibodies against angiogenesis and EGFR pathways. Basically, I presented information on 4 drugs: 2 are monoclonal antibodies against the VEGF receptor and 2 are against the EGFR pathway. These drugs are bevacizumab, ramucirumab, cetuximab (Erbitux), and necitumumab.
Aside from these available agents, are there novel therapies coming down the pipeline?
Angiogenesis and the VEGFR and EGFR pathways are the old members of all of the new biological therapies. Therefore, along the lines of monoclonal antibodies for those pathways, I don’t believe that there is anything—or I’m not aware of anything—new that is coming down the pipeline.
What is a key challenge that researchers still face with these drugs?
By far, the main thing is the absence of a biomarker that may allow us to select the patients or patient populations with tumors that may be particularly sensitive to these agents that we are talking about. We know that EGFR
mutations or ALK
translocations predict sensitivity to tyrosine kinase inhibitors. In patients who have PD-L1 expression, we know that will predict sensitivity to immunotherapy agents. We do have biomarkers for [some of] these patients.
What do you see occurring in the lung cancer field in the next 5 to 10 years?
There are 2 things that are really expanding right now. One is that we identify more and more mutations in patients who have the development of the malignant phenotype of the cancer. Therefore, if that can be targeted, then that phenotype can be reversed. That is definitely 1 area where a multitude of drugs will be developed over the next several years. I am not necessarily just talking about lung cancer, but all tumors in general.