Options in Second-Line Non-Squamous NSCLC

Transcript:Sanjay Popat, PhD: When considering second-line therapy, there are many factors to consider, specifically, engaging with the patient to find out what their views are on the appropriate therapy for them. There are different therapies available at this stage in 2016, with more to come, I’m sure. Currently, therapies include docetaxel monotherapy, pemetrexed therapy, and cytotoxic-pemetrexed if they haven’t had pemetrexed up front. Also, in a select group of patients, one may want to use antiangiogenic therapy, as well. In those cases, one could consider nintedanib if the tumor’s an adenocarcinoma, or ramucirumab for adenocarcinomas or squamous cell carcinomas. In addition, immunotherapy is demonstrating high activity here. Both pembrolizumab and nivolumab have demonstrated superiority over docetaxel, and in some cases, this may well be contingent on the extent of the PD-L1 expression.

Finally, one needs to consider the performance status of the patient because for some patients, docetaxel monotherapy or a docetaxel monotherapy backbone may not be appropriate. And, there is data from the ULTIMATE trial, which showed a superiority in terms of progression-free survival for weekly paclitaxel in combination with bevacizumab compared to weekly paclitaxel alone.

Martin Reck, MD, PhD: Unfortunately, all of our patients will progress after first-line chemotherapy, and all patients will be candidates for subsequent lines of therapies. We have different options. The question is how to choose the appropriate second-line therapy. While we have several options, and the selection is based on several factors, one important factor is the histology of the tumor.

When we see a patient with a squamous cell lung cancer, we have the opportunity to use an anti—PD-1 antibody like nivolumab, and this has shown superior efficacy compared to chemotherapy. The story is a little bit more difficult when we look on patients with pretreated adenocarcinoma. There, we do have several treatment options. We may use chemotherapy, we may use chemotherapy plus a noble antiangiogenic compound like nintedanib or ramucirumab, or we use immune therapies like nivolumab. The selection is based on individual patient characteristics. It’s also related to the performance status of the patient, the growth, and the dynamic changes of the tumor at the tumor burden. In principle, these are my selection factors.

Anders Mellemgaard, MD: Once a patient progresses following first-line therapy, we’re looking at the second-line scenario. We have choices, and the number of choices have been increasing recently. It used to be that we had docetaxel, which was established more than 10 years ago as a treatment that would increase survival for this patient population. Laser pemetrexed was shown to give the same benefit, but with less toxicity. And, erlotinib has also been shown to improve outcome for patients in comparison with their supported care.

But, the recent addition to second-line is interesting and that’s the immune checkpoint inhibitors. With those compounds, we see in some subgroups of patients a better outcome than we have done previously with chemotherapy.

It’s really difficult to figure out if a sequence has any particular meaning. I think the conventional wisdom here is that you should use your best therapy first. You shouldn’t delay something that you really believe in because sometimes patients don’t make it long enough to actually benefit from that treatment. So, you should always select the treatment that you believe in first, rather than saving it for later. But, I think we really lack information about the importance of sequencing.

For example, with immune checkpoint inhibitors, it’s possible that it’s important to use some kind of cytotoxic treatment before giving the immune-stimulating treatment. But, we really do not know that. And, in order to test that, we would have to design trials that look at sequence treatment rather than what we’re doing now, which is to look at little bits and pieces of the total patient trajectory; have the diagnosis of their disease until they eventually stopped treatment and die.

We really do not have a lot of information about sequencing. But, I think it’s important always to make an individual evaluation of the patient, to listen to their own preferences, and to select the treatment that you think, in this particular instance, would be the best for the patient.

Transcript Edited for Clarity