Use of Bevacizumab in Stage IV NSCLC With No Actionable Mutations

Alexander Drilon, MD:Bevacizumab is approved for patients based on histology. So, those patients with nonsquamous tumors, those are the people who would be eligible for the addition of bevacizumab. Whereas if it were a squamous cell lung cancer, I would consider something like a platinum doublet with a taxane or gemcitabine, in certain cases, with or without necitumumab.

As I mentioned earlier, there is a survival benefit with the addition of an antiangiogenic agent. So, for bevacizumab, in the ECOG 4599 trial, it was an improvement in 2 months. And we’re also seeing, if you look at the REVEL data and the ECOG 4599 data, that you can improve the likelihood of response or the response rate if you add an antiangiogenic. Now, that does come with a cost, so there are side effects that are mediated by the inhibition of the vascular system like hypertension, a low risk for clotting or bleeding events that we monitor closely over time. Potentially, hypertension is something that we more commonly see in the clinic, but that’s something that’s easy to manage with antihypertensives for the vast majority of the patients.

As with any patient with non—small cell lung cancer with stage IV disease, the goal is really palliation. So, the way I explain this to patients is we try to keep your cancer at bay for as long as possible, but we’re not smart enough to know how to get rid of your cancer, we’re not smart enough to know how to cure you. The goals are to maintain her quality of life and keep the cancer under control vis-à-vis partial response, or stable disease, for as long as possible, recognizing that, at some point, the cancer will learn to become resistant to every therapy we throw at it, and we have to keep switching gears.

For patients who receive bevacizumab with chemotherapy upfront, to monitor for efficacy, we do scans every 2 cycles. And, for toxicity, when they come in every 3 weeks for their therapy, there’s a detailed physical examination to see how they’re doing in terms of their ADL (activities of daily living), and we also look at laboratory parameters like the CBC in a comprehensive metabolic panel. And we follow these serially, over time, and watch out for adverse events, like hypertension, that we mentioned earlier.

As a summary, the use of bevacizumab in lung cancer as was first based on a randomized phase III trial, which was the ECOG 4599 trial, these were patients who were treatment naïve with a diagnosis of advanced nonsquamous lung cancer. And they received, or randomized, their CarboTaxol with or without the addition of bevacizumab. Ultimately, the most-prized outcome in oncology is an improvement in survival. We observed that with a trial where the overall survival went from a 10-month median in patients who did not receive bevacizumab to a 12-month median, approximately, in patients who received bevacizumab. This was accompanied by an increase in bevacizumab-related side effects, many of which we’ve spoken about earlier.

Case Scenario 2:

SR is a 58 year-old female, former smoker 20 PPY (stopped smoking 5 years ago), presents with cough and SOB. She experienced an unintended 10 lb weight loss over a 3-month period.

• Tissue analysis identified adenocarcinoma, EGFR, ALK, ROS1 negative.
• PD-L1 expression was < 50%.
• Patient has stage IV disease with metastasis to the liver.
• A chest CT scan confirmed the primary mass in the upper lobe of the right lung, with several pleural metastases and malignant pleural effusion.
• MRI of the brain was negative for intracranial metastases.
• Patient has not complained of blood in the sputum.
• Patient has history of well controlled HTN.
• Her performance status was 1 at diagnosis.

Patient was started on carboplatin/paclitaxel/bevacizumab for 4 cycles. Patient showed partial response and was continued on bevacizumab until progression.