Second-Line Therapy in Stage 4 NSCLC

Roy S. Herbst, MD, PhD:This patient had a very poor response to chemotherapy, which, quite frankly, is not uncommon. Chemotherapy really does not have that much of an effect in metastatic lung cancer. Normally I tell my patients that about a third of the time they’ll have response, a third of the time they’ll have stable disease, and a third of the time it will progress. But really, even if there is a response of stable disease, it’s never long-lasting.

This patient had the worst-case scenario—progression on carboplatin/pemetrexed. That speaks to the reason why lung cancer’s been such a difficult disease to treat. Even with advances in chemotherapy, this is the best-tolerated and, perhaps, the most-potent chemotherapy regimen that we have for nonsquamous lung cancer. The outcomes are quite poor.

When this patient progressed on chemotherapy, what were the choices? One choice could have been immunotherapy. Granted the PD-L1 status is 0%, but nivolumab and atezolizumab are both approved, even in that setting. The other approach would be second-line therapy with docetaxel and ramucirumab. Some might give docetaxel alone. I would say you can make a strong case for docetaxel/ramucirumab based on the REVEL study and some of the subanalyses of the REVEL study, which showed results that favor the combination, even in those patients who had rapid progression, such as this patient.

I think that all of those would be possibilities. You’ve got to look at the patient’s performance status. Are they a candidate for docetaxel or not? Having used docetaxel for 20-plus years, it’s a good drug but it’s a tough drug. It produces neutropenia, weakness, and fatigue, so it is a tough one to give. That’s why many people are going to using immunotherapy right off the bat. Certainly, in a case like this, based on KEYNOTE-189 data, one might have given the immunotherapy earlier. If that were the case, you wouldn’t have that as an option. Then, the option would be docetaxel/ramucirumab.

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