Pembrolizumab for Relapsed/Refractory Metastatic NSCLC

Benjamin Levy, MD: The options for patients with relapsed non—small cell lung cancer who have progressed has evolved over the past couple of years. We need to keep in mind that single-agent immunotherapy started in the second line. That was the standard regimen to use when patients were progressing on a platinum doublet. But with all the new front-line data, second-line options have also changed. So patients who are on front-line pembrolizumab, those patients who do progress, or their cancer progresses, I generally will offer them a platinum doublet with carboplatin and pemetrexed. For the adenos [adenocarcinoma] and for the squamous patients, I would offer a carboplatin plus a taxane.

For patients who are on a triplet regimen with carboplatin, pemetrexed, and pembrolizumab, this is where I think we still need a lot of work. The current options include single-agent docetaxel. Docetaxel plus ramucirumab. Gemcitabine is certainly an option. But I would say most of my patients, post-triplet therapy with carboplatin, pemetrexed, and pembrolizumab are offered a taxane-based regimen. And I think that’s where we have the most data. Certainly we need to further the options with good science and good trials. We have 3 or 4 options in the second-line post-triplet therapy, and certainly I look forward to seeing more options on the table in the next 12 to 24 months, hopefully.

Anne Tsao, MD: In the salvage setting for non—small cell lung cancer, if you were to look at the NCCN [National Comprehensive Cancer Network] Guidelines, it lists several agents, some of which are older. But certainly there is docetaxel with or without ramucirumab. You could certainly consider using afatinib. Also, in addition, there are the immunotherapies such as pembrolizumab in PD-L1 [programmed death-ligand 1]–positive patients. Also nivolumab, with or without ipilimumab, I would add. And then certainly atezolizumab. Now, if you are treating a patient in a front-line setting already with immunotherapy or an immunotherapy combination, then most likely in a salvage setting the immunotherapies are probably not your best choice to go to.

We don’t have any data about sequencing these immunotherapies yet, but the thought is eventually we will have information from our clinical trials and with the new novel immunotherapy combination regimens. But for right now, as of today, if you are giving immunotherapy up front and if it’s with chemotherapy, then certainly you would probably want to reach for 1 of the nonimmunotherapy agents in the second-line setting.

Roy Herbst, MD, PhD: So for relapsed and refractory lung cancer, the options would be docetaxel, probably docetaxel with ramucirumab based on the positive results of the REVEL trial, because ramucirumab is a VEGFR2 antibody. But for patients who have already had chemotherapy or immunotherapy, then what do you use? There isn’t a lot right now. There are clinical trials now looking at immunotherapy, so you would take immunotherapy. Some would add chemotherapy in. There aren’t any proved data for that, but that’s what’s being done. Some might take immunotherapy and think about trials with a combination with an angiogenesis inhibitor or perhaps with an agent that affects the immune microenvironment. I guess that’s going to be what keeps us busy as oncologists and scientists for the next decade, all those patients who fail immunotherapy and chemotherapy and still need something else. And I would say the way to really do that best would be to do a biopsy of the tumor and understand what’s working and what’s not. Is there PD-L1? Are there immune cells? And based on that dichotomy, try to design a new regimen based on that.