Lung Adenocarcinoma: Second-Line Therapy Options

Mark A. Socinski, MD:As I previously mentioned, this patient represents treatable disease but not curable disease, and at some point, he is going to progress. Hopefully, when you’re followed closely, the disease progression is detected when the patient still has a good performance status. In the second-line setting—and I clearly think there is value to second-line setting—the current standard of care is use of one of the immunotherapy drugs. We have data with nivolumab, pembrolizumab, and atezolizumab all compared to the old standard of docetaxel. And all 3 of those drugs easily beat the old standard docetaxel. So, over the past couple of years, the standard has changed from docetaxel to use of one of these immunotherapy agents in the second-line setting.

If the patient had—and this patient does not—a contraindication, some autoimmune disease that he couldn’t get immunotherapy from a safety point of view, then I typically, in that setting, use the combination of docetaxel plus ramucirumab. That’s a phase III tested regimen, docetaxel alone versus docetaxel plus ramucirumab. It had superior response, PFS, and overall survival rates. So, that’s my go-to regimen. And I would use that in the third-line setting following immunotherapy if the patient were eligible to get immunotherapy. I use it either second- or third-line. But I think right now, the best second-line option for these patients who have no contraindications to immunotherapy is use of either one of the PD-1 drugs, nivolumab or pembrolizumab, or the only PD-L1 agent, atezolizumab, in this particular setting.

You might get different opinions about which one is best in that setting, but the reality is that they all look very similar with regard to both efficacy and toxicity in this setting. So, I think that it’s nice to have choices, and we’re in the land of plenty in this area with regard to options for these patients. But that’s the standard in the second line.

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