A Case of Advanced Non-Driver Non-Small Cell Lung Cancer

Benjamin P. Levy, MD:This is a patient, a 55-year-old female never-smoker, who presents to her primary care physician with a chronic cough and a 10-pound weight loss. The primary care physician orders a chest X-ray that reveals a very large opacity in the left upper lobe. The patient then has a CT scan that reveals a 5-cm mass in the left upper lobe with bulky mediastinal lymphadenopathy. Following this, the patient does have an EBUS bronchoscopy that samples these mediastinal nodes, and the biopsy is consistent with a TTF1-positive, CK7-positive adenocarcinoma. The adenocarcinoma is sent for next-generation sequencing. It is negative for all driver mutations, includingEGFR,ALK,BRAF, andROS. And a PD-L1 by IHC is 0%.

The patient then has a full-staging brain MRI and PET/CT. The brain MRI reveals no intraparenchymal metastases, and the PET/CT confirms the mediastinal adenopathy in the left upper lobe but also reveals a 4-cm adrenal metastasis. This metastasis is biopsied to confirm adenocarcinoma, which it is. Based on the fact that the patient has a stage 4 adenocarcinoma and has no contraindications to antiangiogenic strategies, the patient is started on carboplatin/pemetrexed/bevacizumab. The patient receives 6 cycles of this triplet regimen and has a nice response and then goes on to receive maintenance pemetrexed and bevacizumab for 9 more months.

Unfortunately, at that time, the patient complains of worsening cough and further weight loss. A repeat CT scan of the chest, abdomen, and pelvis shows that the tumor has enlarged in both the lung and the lymph nodes. The adrenal metastasis is also enlarged, and the patient has new liver metastases. Based on this disease progression, the patient has been placed on atezolizumab, which she receives for up to 12 more months.

It’s important to know that young patients who do present with lung cancer unfortunately present with advanced-stage disease. We’re just not capturing most of these patients with early-stage disease. Most of my young patients, particularly never-smokers, present with significant cough. Often times, they have bone pain from disease metastases to the bone. And, unfortunately sometimes, specifically for patients who areEGFRorALKrearranged, these patients can present with headaches, blurry vision, and dizziness and have brain metastases at the time of diagnosis. I think a lot of the times, many of the symptoms that younger never-smoker patients have are ignored by their primary care physicians. Often times, they’ll be treated with several rounds of antibiotics before they finally get a chest CT and a biopsy, because they’re a never-smoker.

I think we need to remember that 20% to 25% of all non—small cell lung cancer is never-smokers, and this is just not a fact that’s well known by the primary care physicians and the pulmonologists. So, I can’t think of one time where I’ve had a young patient who’s a never-smoker in their 50s, or even 40s, where we’ve caught a stage 1 lung cancer. I think most of the time we’re capturing these at a much later stage, unfortunately.

Transcript edited for clarity.

• A 55-year old female presented with chronic cough and 10-lb weight loss
• PMH: never smoker; no family history of cancer; no known exposure to chemicals or asbestos
• Chest x-ray showed a 5.0-cm lesion in the left lower lobe with bulky lymphadenopathy
• Chest CT scan confirmed the presence of a lung mass and enlargement of the right hilar lymph node and bilateral mediastinal lymph nodes
• EUS-guided biopsy was performed
• Pathology revealed adenocarcinoma
• Molecular testing:
  • FISH: negative for ALK translocation
  • NGS: negative for EGFR, ROS1, RET, BRAF, KRAS
  • IHC: PD-L1 expression in 0% of cells
• PET/CT imaging showed 18F-FDG uptake in the lung mass, right hilar lymph node, mediastinum, and left adrenal gland
• MRI of the brain was normal
• ECOG PS, 0
• The patient was started on therapy with carboplatin/pemetrexed and bevacizumab
• The regimen was well tolerated
• After 6 cycles, the patient had a good response
• She was continued on bevacizumab
• After 9 months on therapy, the patient developed cough and weight loss
• Follow-up imaging revealed multiple new lesions in the left adrenal gland and new liver metastases
• Patient was started on atezolizumab, planned for 12 months