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Sequencing Therapy in NSCLC


H. Jack West, MD: One of the options that still remains is the possibility of sequencing with pembrolizumab, or, potentially, another immunotherapy, followed by chemotherapy; or the reverse of that, particularly in patients with a low level or negative—PD-L1 expression. We should bear in mind that in the KEYNOTE-189 trial, although crossover was part of the trial, 50% of the eligible patients crossed over. This means that 50% did not. For the rest, we have the approval of several immunotherapies. We have several checkpoint inhibitors that are FDA approved after chemotherapy, and the vast majority of my patients actually do cross over. If they didn’t get it in the first-line, nearly every eligible patient will be getting it as second- or third-line therapy. In my experience, my crossover rate in the clinic is far more than 50%. It’s very likely that patients will do comparably well if you cross over the vast majority of them.

One of the big advantages of concurrent therapy is that you can ensure that every patient you start that in is going to get their opportunity to benefit from both chemotherapy and immunotherapy. You can never be sure that’s going to happen if you’re sequencing. A majority of patients will be getting a concurrent chemoimmunotherapy option upfront. Some will have it sequenced, particularly with pembrolizumab as monotherapy, or, potentially, other immunotherapies, followed by chemotherapy—if patients can be spared that.

What’s going to be interesting is, for this new group, this growing population of patients who start with chemotherapy and immunotherapy and then progress, what do we do after that? We still have docetaxel-based regimens, with or without ramucirumab. I think we’re going to see a growing use of that concept, particularly in combination, as patients who still have a good performance status progress through the first-line and have a more limited set of options after that.

In a post hoc subset analysis, the REVEL trial demonstrated that the patients who had early progression got a greater benefit from the addition of ramucirumab, versus the broader population—with an over 3-month difference. This is a subset analysis, but this is a group of patients who were eligible for the trial. The data suggested that these patients could perhaps benefit from ramucirumab more than the broader population. It gives me more confidence for managing a patient who has progressed early, where I’m running out of options. A combination of docetaxel with ramucirumab has a better chance of leading to favorable results. I’ve seen that as well in some of my own patients, and I am very impressed with what the combination has been able to do for a group of patients who have been pretty refractory to chemotherapy alone.

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