Supportive Care in Metastatic NSCLC

Roy S. Herbst, MD, PhD:It’s really amazing to see the progress that’s being made in lung cancer. A few colleagues and I just recently wrote a review article that was in the January issue ofNature. It was called, “The Biology Management of Lung Cancer.” We provided a timeline of the last 20 years. It strikes me that 20 years ago, when I was a Fellow, all we had was chemotherapy. We were actually quite excited because it was new chemotherapy. But now we have targeted therapy. We have immunotherapy. Let’s not forget that we have radiation available for selected patients—even with metastatic disease to sort of stimulate cytokines and, perhaps, abscopal effects. And, of course, we have supportive care. How to integrate all of this together is really the art of medicine.

A key thing is quality of life and patient care. Even if we don’t cure the patient, we want to make sure that his or her quality of life and toxicity management is as best as possible. We’re learning how to deal with the toxicities of these different agents. Immunotherapy certainly has toxicities. Keep in mind that there are some patients who can’t get immunotherapy—someone who already has an autoimmune disease, such as rheumatoid arthritis, or multiple sclerosis, where you could use it if you really had nothing else to use but you risk activating an already present autoimmune process and making that work. In those patients, you might go right to the chemotherapy or the chemotherapy/ramucirumab combination.

Then, of course, there are patients who are getting immunotherapy who aren’t benefiting. They’re ones in whom you might switch to a combination. And then, of course, we’re getting better at dealing with the chemotherapy combinations as well. Nowadays, I think we are able to treat patients more effectively with docetaxel. Some patients actually do quite well with it. Some patients do have neutropenia, edema, fatigue, and other problems. Symptom management has become such an important part of oncology. It wasn’t long ago that we had data that showed, and still show, that palliative care, early on, in patients with metastatic disease, improves survival. In my practice, for someone who comes in with metastatic disease, certainly in someone like this, we would have this patient see someone from the supportive palliative care group right away to manage side effects. Managing side effects is important. Certainly, you don’t want to leave anything on the table. It would be great if immunotherapy worked for everyone, but it does not.

I certainly am a believer in trying to get those immunotherapy drugs to patients as quickly as possible. Even in PD-L1 0% patients, I’m still using immunotherapy upfront. I think that more and more data are going to emerge, and that almost everyone will get immunotherapy upfront.

But then you’re sitting in the clinic and someone’s resistant to immunotherapy. Why are they resistant? There are so many clinical trials. There are different drugs and different combinations that we can test. Right now, it’s all about clinical trials, but that’s not what you have when you’re sitting in your office, in a community practice in the rural areas outside Chicago. You need something that day, while you are looking for the trial. That’s where I think we need to keep docetaxel or the docetaxel/ramucirumab regimen in mind. Frankly, I don’t think you add too much risk by adding the 2 drugs. It’s a proven standard of care. It’s a combination that’s been shown to have activity, even in patients who have progressed on frontline therapy.

So, that’s where you would use that combination. We are going to continue to probe patients and say, “Why was the immune system resistant?” “Are there regulatory cells?” “Is there a lack of T cells, or a lack of information?” “Are there other things that we can do?” We’re seeing that across all tumor types right now, as we’re figuring out how to best target the immune microenvironment. But as a clinician, it’s important to have all of these tools available to you. You need to have them right then and there, when you’re seeing these patients. A small response can have a big effect on symptoms, and can certainly keep that patient going as you look for the next trial or the next combination. That’s why it’s so important to be aware of the most updated 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