Using First-Line Immunotherapy in Stage 4 NSCLC

Roy S. Herbst, MD, PhD:What we have here is a typical lung cancer patient with metastatic disease and no driver mutations. The patient is treated with chemotherapy, which he fails, and gets second-line chemotherapy with docetaxel and ramucirumab, a VEGF inhibitor. And then, of course, the next step would probably be to use an immunotherapy option. One could have made the case to have given immunotherapy beforehand.

Now, in 2018, where we are right now, a patient like this would get immunotherapy upfront. Based on the data from the KEYNOTE-189 trial, if I was seeing this patient in my clinic, I would give him chemotherapy with pembrolizumab. In that trial, even though the progression-free survival data were not extremely compelling in the PD-L1 0% patients, there was a survival benefit for the immunotherapy/chemotherapy combination versus chemotherapy alone. In my opinion, immunotherapy should be given to all patients who qualify, because immunotherapy has the opportunity to produce a more durable and lasting survival in patients. It won’t do so in all of them. It’s a small percentage—10%, 15%. But I try to give immunotherapy whenever possible, as early as possible.

This case is very interesting because it’s right on the cusp of how the field’s evolved just in the last month, since the AACR meeting and the presentation of the KEYNOTE-189 data. Even though one could have used carboplatin, pemetrexed, and pembrolizumab in the setting, few were doing it because the data was all based on a phase II trial of 120-plus patients. But now, with the 600-plus patient data from KEYNOTE-189, I think most would probably use chemotherapy and immunotherapy in a patient like this.

Again, it shows how the field is evolving and how new data are constantly reaching us in the clinic through programs like this, for example, and people are now evolving in how they treat these patients.

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