Personal Experience with Bevacizumab

Mark A. Socinski, MD:As previously stated, bevacizumab has 4 positive phase III trials showing that it improves outcomes whether you look at response, progression-free survival, or, in 2 of the trials, overall survival. So, I definitely think it’s an option for patients who are eligible to receive it.

You have to be selective in patients who you recommend this drug in. There are lots of reasons not to use it. But in patients who don’t have the reasons not to use it, I think it’s an important part of their treatment regimen. The typical toxicities are risk of bleeding, particularly hemoptyses; the boxed warning includes GI perforation, that’s an uncommon event. I’ve certainly seen that in my practice, but it’s quite uncommon. There are no ways to predict that. Hypertension is an issue that you have to be aware of and follow, although it’s usually not unmanageable. You have to be careful in following renal function on patients and looking for proteinuria.

There are a number of very uncommon things, like reversible posterior leukoencephalopathy and other things, that happen with this drug, but they’re exceedingly uncommon. And for the most part bevacizumab is a relatively well-tolerated agent as a single agent. Our strategy with bevacizumab when we use it with carboplatin/paclitaxel is I typically administer 4 cycles. And then, I would continue bevacizumab as maintenance therapy until disease progression. I find that once patients get to that maintenance part of treatment, and they’re only receiving the bevacizumab and not the carboplatin/paclitaxel, they tolerate it exceedingly well. So, I think, in general, it’s a well-tolerated agent.

The initial trial ECOG 4599, which tested the addition of bevacizumab to carboplatin/paclitaxel, excluded patients with brain metastases because there were some early issues regarding the safety in that population. So, when bevacizumab was approved in nonsquamous non—small-cell lung cancer around 2005, it was initially approved in patients who did not have presence of brain metastases. If you look at the nonsquamous population, about 20% of them have brain metastases at the time of diagnosis.

We actually early on launched a trial called the PASSPORT trial. And the primary objective of the PASSPORT trial was to see if you could safely give bevacizumab in patients in the first- or second-line setting of treated brain metastases. We treated, I think, 116 patients where the primary endpoint of the trial was rate of CNS hemorrhage, and we saw no significant CNS hemorrhage. And so, actually the label was changed based on the PASSPORT trial and, as I stated earlier, that we have established safety. If the brain metastases are treated and controlled—and we know that this gentleman had a follow-up MRI that showed no new brain lesions following his stereotactic radiosurgery—under those conditions, I would say that bevacizumab is safe in this setting. Initially, this was an agent that we very cautiously used in patients with a brain metastases. We don’t have any studies about the safety of bevacizumab in patients who have untreated brain metastasis. And that’s why earlier in the case discussion I said that treating the brain metastases, if you’re considering using bevacizumab, is a critical part of management.

Transcript edited for clarity.

• A 64-yr old gentleman presented with headache, impaired vision in left eye, and intermittent confusion that had begun a few weeks ago
• He is a current non-smoker with a 30-pack-year history
• Past medical history: hypertension diagnosed 3 years ago, well-controlled on losartan
• His cardiac workup is negative
• His PS by ECOG assessment is 1
• Head computed tomography demonstrated a mass (1.0 cm) in left occipital lobe with associated edema
• Full body CT scan revealed a left lower lobe lung mass (2.2 cm), and ipsilateral mediastinal lymphadnopathy
• Whole body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan revealed increased FDG uptake in the primary left lower lobe lung mass, mediastinum, and several bony sites
• Core biopsy of the lung mass was performed and indicated
  • A histopathological diagnosis of adenocarcinoma (staining for TTF-1 was positive)
  • Genetic testing was negative for known driver mutations
  • PD-L1 testing by IHC showed expression in 15% of cells
• Brain MRI revealed 2 additional 8 mm lesions in the left frontal and right temporal lobes
• He was diagnosed with stage IV NSCLC adenocarcinoma
• He was treated with stereotactic radiosurgery (SRS) for brain metastases
• Two weeks following SRS
  • A follow up MRI scan showed no evidence of new brain metastases
  • CT scan showed:
    • 4 smaller nodules in the left upper lobe
    • The left lower lobe lung mass increased in size to 3.3 cm
    • Ipsilateral mediastinal lymph node swelling
• The patient was started on therapy with carboplatin/paclitaxel and bevacizumab