Treating with Bevacizumab in Lung Adenocarcinoma

Mark A. Socinski, MD:This patient had a follow-up brain MRI following the SRS treatment. And the rationale for doing that was to make sure that his brain metastases were controlled and that there were no new findings. In this case, there were no new findings, so I would consider this patient safety treated. And the use of bevacizumab, I would say would be safe in this gentleman from a CNS point of view.

The next decision would be on what’s going on in his chest. He had a follow-up CT scan and, not surprisingly, his disease was a little bit worse, both in the primary as well as the mediastinal lymph nodes. He did have a few new nodules in the same lobe as the primary lesion, which is not unusual. And we sometimes see as the brain is getting treated, since the chest hasn’t been treated yet, it’s at risk of progressing. But this patient had pretty minimal disease to start with, so I wouldn’t consider this progression without treatment to be significant.

As I said before, I think his options are either carboplatin with pemetrexed or carboplatin with paclitaxel. The FDA-approved regimen actually with bevacizumab is in combination with carboplatin and paclitaxel. And that patient was treated with that regimen, which I completely agree with. I think it is a category 1 NCCN-recommended regimen. It is based on phase III data. We know that there’s about a 35% response rate from the ECOG 4599 data. It significantly improved PFS, as well as overall survival, in ECOG 4599. So, I’m completely comfortable with his treatment at this time.

In general, what I do is reassess patients typically after 4 cycles. I find that with a regimen like carboplatin/paclitaxel, most patients tolerate 4 cycles relatively well without undue cumulative toxicity. But going beyond 4 cycles, patients start to get into some trouble with cumulative anemia, neuropathy, and fatigue. We had a number of trials done a decade or more ago that looked at either 3 or 4 cycles of platinum-based therapy versus 6 or more. There was no convincing evidence that 6 or more did better from an overall survival point of view or response point of view, maybe a little bit of benefit in PFS. So, I typically stop at 4 cycles. But, again, bevacizumab is a drug that we use until disease progression.

I would continue bevacizumab as a single agent as maintenance therapy. We refer to it as continuation maintenance therapy. And certainly, my experience has been that patients will get several doses. Occasionally, some patients will get a couple years of bevacizumab maintenance benefit. There’s a great deal of variability. And we know from the original ECOG 4599 trial that there were 2- and 3-year survivors remaining on bevacizumab. So, there is a minority of patients who seem to get some long-term benefit from this agent.

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