Treatment After Progression on Anti-VEGF Therapy


Benjamin P. Levy, MD:If a patient has progressed on platinum-doublet therapy, receives docetaxel/ramucirumab, and has not received immunotherapy, I may consider giving them immunotherapy. But if a patient has already received immunotherapy, I’m probably not going to go back to immunotherapy again, even if it’s with a different drug. I would probably think about a clinical trial or more chemotherapy. I don’t ever go back to the same drug that I’ve used before. However, there are some exceptions. If a patient had a very nice response to immunotherapy for a long period of time, then went on docetaxel/ramucirumab and progressed, I may consider going back to immunotherapy, considering that they garnered such a large benefit from this. But for the most part, if I had a patient who started on the platinum-doublet, then got docetaxel/ramucirumab and didn’t get immunotherapy for one reason or another, I would consider immunotherapy in the third-line setting.

Most of my patients are going to get immunotherapy in either the frontline or second-line setting. Docetaxel would probably come with ramucirumab as a third-line option or could be used in the second-line setting after chemotherapy and immunotherapy. And in that, we just don’t know what to do. We have to think hard about clinical trials, novel strategies, and further chemotherapies that may or may not work in these patients.

Immunotherapy does not work in driver mutation-positive patients—specificallyEGFR- andALK-rearranged patients. Every attempt must be made to do molecular interrogation on all of our adenocarcinoma patients and all of our never-smoking squamous cell patients before we make a decision about immunotherapy. We need more information. Whether immunotherapy combined with chemotherapy will work in this patient population is unclear. Start with a TKI. Start with a targeted therapy if you have an identifiable target. And if you’re going to then decide what to do next, it’s generally not going to be single-agent immunotherapy.

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
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