Using Antiangiogenic Therapy in Stage 4 NSCLC

Roy S. Herbst, MD, PhD:In my practice, which is an exclusive lung practice, you can imagine that I see many patients who have chemotherapy-refractory disease. And certainly, in those patients who are nonsquamous, such as the one we’re discussing today, who’ve already had pemetrexed, your second-line choice of chemotherapy is docetaxel. Certainly, you have the choice of whether to give a docetaxel-based combination, docetaxel alone, or immunotherapy. Many people are going right to the immunotherapy now, just because the curves overlap for the 2, even in PD-L1—negative patients, and the side effects are perhaps less. I think that’s true. That has been my experience for immunotherapy and then chemotherapy.

Now, in most cases, people would give immunotherapy in the second-line and save the second-line chemotherapy, so to speak, the docetaxel, for third-line use. My experience with the docetaxel/ramucirumab regimen has been in immuno-oncology—naïve and immuno-oncology–treated patients. It has been available to us for almost 3 years now, and was also available before that in clinical trials. I’ve used it in both cases.

I think it’s a well-tolerated regimen. It doesn’t add much to the docetaxel. It can be used in squamous and nonsquamous tumors. There are not many issues with bleeding. My sense is that it improves the outcomes—the response rates, progression-free survival, and overall survival, as shown in the REVEL trial.

We must not forget that we still have chemotherapy to offer. Immunotherapy’s all the rage, and we’re using a great deal of it at Yale right now. In fact, if patients can’t get immunotherapy as standard care in the frontline setting, they’re getting immunotherapy in some sort of clinical trial. But do you know what? Most of what I see, on a day-to-day basis, in the clinic are patients who are failing immunotherapy. Only 18% to 20% of patients, in 5 years, are doing great on immunotherapy, which is a phenomenon. Who would have thought we’d see metastatic disease at 5 years, at 20%? That means 80% of the patients are either primary refractory to immunotherapy, or they get immunotherapy and they become resistant.

My experience has been that about half of those patients that you treat with immunotherapy become resistant. At that point, we need another agent. You need new targeted agents, such as ones that targetVEGF. You need another chemotherapy. For the patient who has had immunotherapy and is progressing, you have to make a change. That’s where I would look to a docetaxel/ramucirumab combination, as we’re talking about here. This is in a little bit of a different order from how I would treat the case today. It will probably be different in a week from now, after new data emerge. That’s how quickly this field is moving. That’s why it is really important to stay on top of the most recent data.

Transcript edited for clarity.

Case: A 62-Year-Old Man With NSCLC and Bone Metastases

• A 62-year-old man presents to his PCP complaining of persistent right-sided neck pain. Two months later he developed decreased appetite, lethargy, and a dry cough
• PMH: Smoker, hypercholesterolemia managed on pravastatin, no allergies, no family history of lung cancer
• Imaging
  • MRI of the neck revealed spine lesion
  • Chest CT showed a 4.3-cm right upper lung mass with enlarged right hilar and right paratracheal lymph nodes
  • PET scan showed¹⁸FDG uptake in the RUL mass, the hilar and paratracheal nodes, and multiple cervical and thoracic vertebrae
  • Brain MRI was negative for metastases
• CT-guided biopsy of the RUL mass showed stage 4 adenocarcinoma; TTF-1 positive
• Molecular testing:
  • NGS: negative forEGFRandROS1
  • IHC: negative forALKgene rearrangement
  • IHC: PD-L1 expression in 0% of cells
• Labs show elevated CEA (26), low albumin (3.4), normal creatinine, CBC, and liver function
• The patient was started on pemetrexed with carboplatin q3W and vitamin B/folic acid supplement
• PE/ROS after cycle 1: ECOG PS 1, no palpable lymph nodes, decreased breath sounds in RUL, persistent symptoms
• CEA increased to 28, CBC shows mild anemia (Hgb 11.0)
• Imaging after 2 cycles of chemotherapy showed progression in the right lung mass (5.2 cm) and several bone lesions
• Labs now show increased CEA (34), decreased albumin (3.2), and decreased Hb (10.2)
• The patient was started on docetaxel with ramucirumab