Front-line Treatment Options for SCLC

David Gerber, MD: Steve, I’m interested in your thoughts. When I have patients who have paraneoplastic peripheral neuropathy, because I know cisplatin can cause peripheral neuropathy, I’m likely to change out the cisplatin and substitute carboplatin. I don’t know if I automatically would do that with LEMS [Lambert-Eaton myasthenic syndrome], where I’m not sure if it’s the peripheral nerve so much as the neuromuscular junction. And what about whole-brain radiation or prophylactic cranial irradiation? When I have a patient with paraneoplastic limbic encephalitis, where the pathology of that syndrome is in the brain, I likely won’t do PCI, or prophylactic cranial irradiation, but if it were LEMS, where the pathology is outside of the brain, I might consider it. Steve, am I crazy to think about it that way?

Steven Vernino, MD, PhD: No, not at all. These are all great questions, but I’m not sure we have definitive answers for them. It requires a case-by-case approach and good communication and discussion between not only the patient and their physicians, but between the oncologist and the neurologist. For Lambert-Eaton myasthenic syndrome, the ultimate treatment goal is to try to remove the stimulus to the immune system, which is the small cell lung cancer, and then manage the symptoms. That’s what we would want to do, we’d want to be aggressive about the lung cancer treatment, and follow the approach that gives the patient the best chance of freedom from the malignancy. In my experience, because I’m looking at this from a different aspect, where everyone I’m seeing has a paraneoplastic neurologic syndrome, I’ve been struck over the years by the number of patients with small cell lung cancer who do have a long-term remission of their tumor and sometimes no recurrences, which is almost unheard of in small cell lung cancer, except in the scenario of a paraneoplastic immunological syndrome.

The thoughts about treating the LEMS, the neurologic aspect of this should focus on how much disability this person is having based on their weakness. This is a classic case with the symptoms we described, difficulty getting up the stairs, out of a chair, fatigability, and so on. Those are symptoms that are probably giving him a lot of trouble, and we’d want to be aggressive in terms of the symptomatic management while he’s undergoing cancer treatment. What I would do as a neurologist while seeing this patient, I would think about the other possible paraneoplastic syndromes we see in patients with small cell lung cancer and do a good thorough neurologic examination to establish what the baseline is. Yes, we can find things that help us to make the diagnosis of LEMS, but we should check cognition, cerebellar function, and do a careful sensory examination to see if there are signs of a peripheral neuropathy even before chemotherapy has started. That is helpful for the oncologist to know, that there’s already a significant neuropathy. Some patients with small cell lung cancer can get a paraneoplastic sensory neuropathy, which can be disabling, and we wouldn’t want to make that worse.

On the other hand, to treat the Lambert-Eaton myasthenic syndrome, I want to use the strongest cancer therapy that will treat the cancer and provide immunosuppression to reduce the activity of the immune system. That’s where we get into a bit of a conflict, like do we want to use checkpoint inhibitors, which can be valuable and revolutionary in improving the outcome of the malignancy, but are basically unleashing an immune system that already has a tendency of attacking normal tissues in the nervous system? I would encourage my colleagues in oncology to avoid a checkpoint inhibitor in this patient until we really need it and we’re pretty sure that we have the neurological syndrome under good management.

David Gerber, MD: As an oncologist, when I decide whether to give immunotherapy, a checkpoint inhibitor, I’m considering the potential benefit and risk. Unfortunately, the additional benefit of immunotherapy in small cell lung cancer is relatively limited. It’s not what we see in non–small cell lung cancer, and definitely not what we see in melanoma, where it has turned a devastating disease into something that can be cured in a substantial proportion of metastatic cases. I’m not necessarily putting the patient at a great disadvantage by not starting with upfront immunotherapy, if that’s otherwise indicated. I also ask myself, what is the risk? This comes up with autoimmune disease frequently. If I have a patient with psoriasis, and I trigger or worsen their autoimmune disease, their skin will get worse. We can handle that clinically. If they have a difficult to control myasthenia gravis, and I give them checkpoint inhibitor therapy, they may go into phrenic nerve paralysis, diaphragmatic failure, and hypoxic death. I worry more about LEMS as an autoimmune condition in the nervous system than I do about others, such as rheumatoid arthritis or those skin conditions that I mentioned.

Steven Vernino, MD, PhD: I think that’s right. You weigh the risks and benefits.

Transcript edited for clarity.