Treatment options for advanced NSCLC fit into 3 main categories…
- Targeted Therapy – we test lung cancer for specific mutations to see if we have an appropriate targeted medication.
- Immunotherapy – if targeted therapy is not an option immunotherapy should be part of the initial treatment strategy. We test the cancer for a specific protein called PD-L1 and if present we consider immunotherapy with a “checkpoint inhibitor” as the appropriate first treatment.
- Chemotherapy – when targeted therapy or immunotherapy is not the best initial treatment we consider chemotherapy.
What is biomarker testing and should lung cancer patients undergo biomarker testing for lung cancer?
One of the great strides we have made in cancer in general and lung cancer specifically is the recognition that the more we learn about your cancer, the better we are able to precisely target therapies that have the best chance of working. Right now there are several tests that would be considered standard across the board for anyone with metastatic non-small cell lung cancer (NSCLC). Looking for mutations in EGFR, BRAF, and for rearrangements or translocations in two other genes: ALK and ROS1. In addition, all patients with metastatic NSCLC regardless of type at this point should be tested for PD-L1 expression.
Is there any evidence that checkpoint inhibitors should be used in stage 2 or 3 non-small cell lung cancer?
Checkpoint inhibitor is another word for the immunotherapy drugs that we had mentioned earlier. Although they were previously relegated primarily for patients with metastatic stage IV disease, more recently, based on the PACIFIC trial we are seeing a role for checkpoint inhibitors, for patients with stage 3 NSCLC who have had chemotherapy and radiation. In the past when these patients completed chemotherapy and radiation we did not have anything additionally to do that had clear value, so we watched these patients closely hoping that their cancer didn’t come back. What we have now learned that patients treated with chemotherapy and radiation for unresectable stage 3 NSCLC, and then receive a year’s worth of checkpoint inhibitor survive much longer and delay a cancer recurrence compared to patients treated with just chemotherapy and radiation.
What therapy should you receive when you fail a checkpoint inhibitor? Can another checkpoint inhibitor work?
I want to be cautious—obviously each case is different and it depends in part on which therapy you have received before. If you have only received a checkpoint inhibitor and have not received anything else, certainly we want to think about chemotherapy options, or if a targeted mutation was discovered, we want to strongly consider an appropriate targeted therapy. In terms of switching solely from one immunotherapy agent to another, it is not clear to us that switching from has any clear role at this time. This is where we should think about clinical trials. There are a number of clinical trials for patients that have failed a standard immunotherapy agent – they should start thinking about clinical trials that maybe combines the immunotherapy agent with something else. I think just switching from one immunotherapy agent to another has not been a clear strategy.
How long should someone stay on immunotherapy and what side effects should they look for?
In general, we think of using immunotherapy as long as it is working and not causing bad side effects. In terms of optimal duration the answers to that are still being explored. When we first started using these drugs in melanoma, the plan was to just use them as long as they worked. When they were studied in lung cancer, many of the clinical trials were written as such that if they continued to work, after two years you got a break because you have to recognize that some of these patients at that point their immune system had been ‘trained’- if you will- and the cancers seemed to remain under control without needing to get more of the medicine. So the optimal long-term duration is unclear, but at least in the short term, as long as it is working and not causing bad side effects, one continues it. It is not a ‘you get two cycles and you stop type of treatment.’
In terms of side effects, the side effects of immunotherapies are qualitatively different than the side effects from chemotherapy because of how they work. Because immunotherapy drugs are trying to train your immune system to search and destroy in a more effective way one of the risks are that your immune system may attack some part of you. The risk is for inflammation of just about anything. That doesn’t mean that every patient gets each of these side effects. It doesn’t even mean that each patient gets any of them. But they are possible and it can be inflammation of scalp, eyes, brain, thyroid, lungs, heart, liver, kidney, muscles, joints, just about anything. The side effects we see most commonly are fatigue, diarrhea from inflammation of the colon, rash, inflammation of thyroid, which can disturb thyroid function. The things that we worry about the most are inflammation of things like brain, heart and lungs. I worry about the lungs because while this is incredibly rare, when it happens it can be severe. So we certainly have to be on the look out for these things.
Excerpts from and Interview with Dr. David Jackman MD, the medical director of clinical pathways and an expert in thoracic oncology at the Harvard-Dana Farber Cancer Institute.
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