Lung Adenocarcinoma: The Evolving Role of Chemotherapy

Transcript:Heather Wakelee, MD: For patients who are going to be receiving chemotherapy for metastatic lung cancer—that’s still going to be close of half of patients with the disease at first diagnosis—in general, we do start with recommending a platinum doublet combination. That’s normally going to be carboplatin in this country, but we’ll think about cisplatin for some and then we have a lot of options to pair with it.

In the United States, we tend to use pemetrexed if a patient has adenocarcinoma. The reason for that is tolerability. There’s no hair loss, and nausea and vomiting are less of an issue. Patients will have a rash and need lab tests, but in general, patients are able to continue living a life that’s fairly normal. There have been studies showing that that combination is better than some other doublets, like a platinum with gemcitabine. So, if patients have adenocarcinoma, we’ll usually recommend platinum/pemetrexed.

We also have data for that combination in patients who are older and in patients who have a performance status that has decreased a little bit. In head-to-head trials comparing that doublet to pemetrexed alone, the combination looked better as far as response and overall outcome, so that’s usually what we’ll recommend. For a patient with squamous cell histology or without anything that fits into that grouping, we’ll usually go with a platinum with gemcitabine. Sometimes, that’ll have a third drug added, necitumumab. But in general, it’s just a platinum with gemcitabine. The taxanes can be used for anybody.

Paclitaxel is still a very commonly used regimen as well. From my perspective, the downside there is that patients do lose hair. There’s alopecia, there’s the risk for nausea, vomiting, and really no difference between the groupings, so that doesn’t help in our decision. With the paclitaxel, there’s some risk for having allergic-type reactions, which could be challenging if they happen, but they are rare. So, I tend to talk with patients about the various options, but I tend to use a platinum doublet unless there’s a contraindication because of other performance status issues—usually other comorbid diseases. And then, we’ll go from there.

David Spigel, MD: There are a lot of chemotherapy platinum doublets that we use in the first-line lung cancer setting. These days, they’ve tended to shift to certain popular recipes, and I think in the nonsquamous setting, the most popular recipe in the community—certainly in the United States—is a combination of carboplatin and pemetrexed. It does not cause alopecia or myelosuppression. Lowering of the blood count happens, but it tends to be very manageable. It’s very unusual for a patient to need to be hospitalized because of neutropenia or infection or to be transfused. It happens, but not very often. Patients tend not to get very sick. It’s not like they get the treatment and they spend the next several days nauseated or vomiting. That can happen, but it’s very unusual these days—not only with this regimen—as the antiemetics are so effective.

I would say fatigue is the more common side effect that we experience, certainly in that first week following treatment. Patients come in for their initial therapy, which takes under 2 hours to receive—probably closer to about an hour and 15 minutes—and then they don’t have to come back for 3 weeks. When you get past 4 cycles of this doublet, a lot of physicians will move to maintenance pemetrexed alone, and that’s what I do. That’s a very easy 10- to 15-minute infusion every 3 weeks. I have a number of patients who come in for that maintenance therapy. The side effect profile gets even better, and—except for the inconvenience of coming in every few weeks indefinitely—a lot of patients find this to be relatively easy. When it works, it can work really well for some people.

Right now, we’re fortunate to have a number of options in the first-line setting for patients with advanced lung cancer. We’re always striving to find a target to go after, so if somebody has an alteration that we have an oral therapy for—namely EGFR, ALK, and ROS mutations—we focus on identifying that in the first-line setting because we believe that those therapies are going to be the most effective first-line therapies, at least for the foreseeable future.

Immunotherapy has found its way into the first-line setting as a single-agent strategy, and for now, that’s pembrolizumab, a drug that has been approved to be used in patients with squamous and nonsquamous lung cancers that have high PD-L1 expression—50% or higher. These are measures that we ask our pathologists to help us with, so we can identify whether or not one of these strategies makes sense. And then, for everyone else, it’s going to be chemotherapy. Chemotherapy continues to be what a majority of patients receive in the first-line setting for both squamous and nonsquamous cancers.

That could change in the very near future. We’re waiting on data from studies on chemotherapy with immunotherapy. In the next several months, there are going to be many studies reading out in the first-line setting of immunotherapy with immunotherapy—what are called immunotherapy doublets or IO-IO combinations. So, the whole first-line setting is going to be a little chaotic for probably the next 12 months. But no matter where we end up, I think chemotherapy is going to be a part of it. It’s unlikely chemotherapy is just going to go away—that it’s not going to be something you use in the first-line setting. I think it’s still going to be widely used. There are just some questions about whether that’s with immunotherapy or by itself, but we’ll get those answers in the next short period of time.

Transcript Edited for Clarity