Anti-VEGF Therapy in Advanced Squamous NSCLC

Benjamin P. Levy, MD:For any patient who starts first-line therapy and has rapid progression, there should be consideration for using a regimen of docetaxel and ramucirumab. Most of my patients admittedly get immunotherapy in the second-line setting. There’s no doubt about that. But even for my rapid progressors, if I think they’re going to respond to immunotherapy, I’ll try it. However, I do think there are considerations. I’ve done this before in my patient population. For a patient who is PD-L1 0%, who got frontline chemotherapy, has a low TMB (tumor mutational burden), has a contraindication to getting immunotherapy, and is rapidly progressing, you really need to consider the combination of docetaxel and ramucirumab, based on the subgroup analysis from the REVEL trial.

The REVEL trial, again, looked at docetaxel with or without ramucirumab. It looked at patients who had rapid progression within 9, 12, and 18 weeks. In all of those patients, there was a benefit when ramucirumab was added to docetaxel compared with docetaxel alone. I would say that’s rare. This is a group that generally does not derive meaningful benefit from interventions, and we saw that here. So, if you have a patient who is on a frontline regimen, and you do 4 cycles and then do a scan and see cancer progression right away, immunotherapy is generally considered first. But if they are a never-smoker with a PD-L1 that is less than 1% or 0% and you need to elicit response quickly, this is a regimen that may need to be considered. We saw a benefit in all subgroups of rapid progressors—a benefit in progression-free survival and overall survival. That’s meaningful.

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