Metastatic Large Cell Lung Cancer: Second-Line Therapy

Lyudmila Bazhenova, MD:We have several second-line options approved in lung cancer patients. We have 3 immunotherapy agents: nivolumab, pembrolizumab, and atezolizumab. Because of the active Crohn’s disease in this patient, I would be very reluctant to give her immunotherapy because of an increased risk of immune-related adverse events, which could be pneumonitis, colitis, dermatitis, thyroiditis, hypophysitis, or myocarditis. The other drug that has been approved as second-line therapy, because it showed improved survival compared with best supportive care, would be docetaxel. So, for this patient, I would consider second-line docetaxel. Another correct answer for all of those patients who we treat with cancer is always clinical trials.

If this patient didn’t have active Crohn’s disease, if she had a history of Crohn’s disease that was in remission, then my decision to use immunotherapy treatments for her would be a little bit easier to make, even though we still know that patients with connective tissue disorders in remission have about a 20% chance of having immune-related adverse events. But I think in this situation, I would be more comfortable using that option. We don’t have any randomized clinical trials comparing the 3 immunotherapy agents I mentioned. At this point, the selection is based on physician’s habit and patient preferences. There is a different schedule for those agents. Nivolumab is given every 2 weeks, whereas pembrolizumab and atezolizumab are given every 3 weeks. There is no efficacy differential, in my view, between those 3 agents.

There are a lot of new developments ongoing in first-line therapy. Just a couple of days ago, we had the release of CheckMate-227 telling us that the study met its primary endpoint of improving progression-free survival in newly diagnosed patients with high tumor mutational burdens. So, in the future, maybe we will have a new biomarker for patient selection with immunotherapy, and tumor mutational burden could be emerging as one of those new biomarkers.

Transcript edited for clarity.

• A 70-year old woman presented with persistent cough and congestion lasting more than 6 months
  • She is a non-smoker; drinks alcohol 1-2 times/week
  • PMH: Crohn’s disease managed on infliximab; hypothyroidism, moderately well-managed on levothyroxine; osteoarthritis managed PRN on naproxen
  • Her physical exam and cardiac workup were normal
  • CBC; WNL
  • PS by ECOG assessment is 2
• Chest X-Ray showed mass in the upper right lung
• CT of the chest, abdomen, and pelvis showed a solid 6 X 8 cm. Right-sided pleural mass abutting the apical aspect of the chest wall and 2 small hepatic nodules measuring 1.5 cm and 2 cm.
• Bronchoscopy and biopsy of the lung mass was performed; pathology was consistent with large cell carcinoma
  • Genetic testing was negative for known driver mutations
  • PD-L1 testing by IHC showed expression in 2% of cells
• Brain MRI showed no evidence of CNS disease
• Diagnosis; stage IV NSCLC
• The patient was started on therapy with carboplatin and paclitaxel and bevacizumab