Frontline Decision Making in Nondriver Lung Cancer

Roy S. Herbst, MD, PhD: In advanced nondriver non—small cell lung cancer, the first thing I would do would be to test for PD-L1. If that’s high—50% or more positivity for PD-L1—for 20% of patients, maybe, 25%, I would give those patients pembrolizumab. The other 75% of patients—outside of a clinical trial, and certainly at Yale Cancer Center, we’re looking for clinical trials—in the absence of a clinical trial, we do platinum-based chemotherapy. Which one to use? Certainly, if the patient has nonsquamous disease, these days we’re using carboplatin/pemetrexed. If someone has squamous disease, of course, pemetrexed is not approved in that setting. Then, you would probably use carboplatin/paclitaxel or maybe carboplatin/gemcitabine. In some cases with carboplatin/paclitaxel, one might want to add bevacizumab, the angiogenesis inhibitor. I would do that if I was using that doublet.

In the frontline setting, PD-L1 expression would be the sole determinant of who would get immunotherapy alone. As far as chemotherapy goes, performance status is critical. If someone has a performance status of 0 or 1, give them a platinum-based therapy. If they have a performance status of 2, I might move away from platinum and just give a single agent. That would be pemetrexed if they’re nonsquamous, and, if they’re squamous, maybe docetaxel. I might even not treat if they’re really in the poor performance status state, but most of those patients would get chemotherapy.

Patients with nonsquamous non—small cell lung cancer, which are the majority of patients, are getting chemotherapy alone. That would be carboplatin/pemetrexed. I will offer maintenance to patients who have a stable disease or response; I usually start to discuss that after 2 cycles. Then, of course, I will offer maintenance, because maintenance has been shown to improve survival.

If someone has squamous lung cancer, I usually don’t do maintenance in that setting. I don’t think the drug docetaxel is as attractive a drug to use—pemetrexed is so much better tolerated. Someday, maybe, we’ll be doing maintenance with immunotherapies or other agents like that. The key to maintenance is added value—added outcome with not a lot of added toxicity. But, usually, I do offer maintenance to the patients with nonsquamous lung cancer.

The option for maintenance in stage 4 disease is pemetrexed. There are some data for erlotinib maintenance, but I think, outside of patients having an EGFR mutation, I wouldn’t use erlotinib in that setting. I really think the only maintenance drug is pemetrexed for the nonsquamous patients. We need better maintenance options. No one is cured with stage 4 metastatic lung cancer, so then the question would be, maybe we want to use an immunotherapy or use something like that? And I think we’re going to start seeing some trials like that in the future.