Progression After Chemotherapy in Advanced Squamous NSCLC

Benjamin P. Levy, MD:The outcomes are very different if patients are rapidly progressing on chemotherapy. We know that this group of patients is generally in trouble and that their outcomes are worse than those who have a response or have stable disease with chemotherapy, and so we need to critically think about what we give them as a second-line drug. Do we give them immunotherapy? Do we give docetaxel/ramucirumab? What’s going to add a meaningful improvement to their outcome is very important.

I consider switching therapy if they have disease progression, are symptomatic, or are not tolerating the frontline regimen. I consider all of those factors. In a squamous cell patient, it’s very clear most of the time. It’s not so clear in the adenocarcinoma population. When a squamous cell patient is progressing, their tumor is growing, and they’re symptomatic. That is when I would make a therapeutic switch.

Sometimes we do a scan and find that the growth is minimal, and they’re not symptomatic. Here, we may just watch them and not deliver a second-line drug. For the most part, the decision is a little more clear in the squamous cell patient population.

For any patient who gets platinum-doublet therapy, whether they have adenocarcinoma or squamous cell histology, if they aren’t receiving immunotherapy in the platinum-doublet upfront, the options in the second line are either single-agent immunotherapy with nivolumab, atezolizumab, or pembrolizumab, or docetaxel and ramucirumab, or docetaxel alone.

For the large majority of patients with squamous cell disease, if I didn’t offer them immunotherapy up front, I would offer it to them as a second-line option. But there may be a patient who doesn’t fit perfectly for immunotherapy. Either they have comorbidities that preclude them from getting immunotherapy—autoimmune diseases, if they’re on steroids—or they may have rapidly progressing disease and their PD-L1 is 0%, like this patient. If a patient has rapidly progressing disease and their PD-L1 is 0%, it’s questionable whether to use immunotherapy or docetaxel with or without ramucirumab. I would probably favor immunotherapy in this patient. Given the subset analysis we’ve seen from the REVEL trial, it’s certainly a consideration to think about docetaxel/ramucirumab.

I think this decision process is going to go away very soon, because immunotherapy is going to be added up front to platinum-doublet therapy for the squamous cell patient population. All that we’ll have left is docetaxel with or without the ramucirumab. Certainly, gemcitabine is another agent that could be considered. For the most part, if I haven’t used immunotherapy up front, I will use it as a second-line option. But for those patients who can’t tolerate immunotherapy, have autoimmune diseases, or are rapidly progressing and are symptomatic and have a low PD-L1, that may be a situation where I would consider a cytotoxic regimen with or without antiangiogenesis.

Transcript edited for clarity.

Case: A 53-Year-Old Woman with mNSCLC Rapid Progression

• A 53-year-old woman presents with a lump in her left deltoid and no other signs or symptoms
  • PMH: insignificant, currently on no medications, no smoking history
• Chest X-ray showed a 5-cm soft tissue mass
• Biopsy showed advanced squamous cell carcinoma, TTF-1-
  • Molecular testing negative for known actionable mutations
• PET CT revealed a liver lesion and adrenal mass
• Brain MRI showed no evidence of CNS metastasis
• Staging: T2aN3M1b
• 22C3 antibody testing; PD-L1 TPS, 0%
• The patient is started on cisplatin/gemcitabine
• Imaging at 3 months shows widespread progression with new and enlarging lesions including a significant increase in her soft tissue and lymph node disease, collapse of her right lower lobe and new liver lesions