Frontline Therapy Approaches for Small Cell Lung Cancer

Transcript:

Jacob Sands, MD: In extensive-stage small cell lung cancer, we often see very good responses to therapy with initial treatment. Historically, if we look prior to any of the checkpoint inhibitors and such, and in the frontline setting with chemotherapy—carboplatin, or cisplatin, and etoposide—we see the majority of patients having responses. In some people we see very dramatic responses. The most extreme case I’ve had is somebody who was actually in the intensive care unit and intubated, who ended up having an excellent response to therapy and, ultimately, was back to the outpatient setting living his life and was very active.

It’s not uncommon to see people admitted to the hospital with a new diagnosis of small cell lung cancer in need of oxygen, who have responses to the initial chemotherapy so that they’re able to leave—off oxygen—and go somewhat back to their lives. Of course, they then have ongoing treatment and such. But the initial responses can be very significant.

The challenge becomes when there’s progression of disease. Unfortunately, for many people, that really comes within months. In many cases, it can be in less than 6 months. And there, the treatment options really become much more limited. If it’s been more than 6 months, then trying chemotherapy again—a platinum etoposide—can sometimes be effective. I have seen some patients with responses in that situation.

Unfortunately, there have been a lot of failed trials within small cell lung cancer. It’s just been a very difficult disease to control, and it’s a very aggressive disease. And so in the second line and beyond, we’ve seen a number of treatments not really demonstrate efficacy. I think the most disappointing recently has been Rova-T [rovalpituzumab tesirine]. This was a drug with tremendous preclinical data. There was a lot of hype and a lot of enthusiasm about this drug that, unfortunately, didn’t really pan out in the studies that we’ve seen.

The regimen that I’ve used most commonly is carboplatin AUC [area under the curve] of 5 [mcg times hours/mL] on day 1, etoposide 100 mg/m² on days 1, 2, and 3 with q3-week cycles [every three weeks]. I would do scans after every 2 cycles. Typically, at that first scan after 2 cycles, we often see a nice response to therapy. Those visits tend to be happier visits, because people are very excited to see how much the cancer has really shrank. After 4 cycles, it often hasn’t necessarily changed so much, and there’s usually some stability between those 2 scans. In those who are continuing to have a nice response to therapy, who did well with the first 4 cycles, I would then consider giving them cycles 5 and 6 of therapy. And that really is the minority of patients. This was really in a preimmunotherapy time frame, where we were just using chemotherapy. That’s really the regimen that I would have used.

With the IMpower133 data with chemotherapy adding in atezolizumab for 4 cycles and then maintenance atezolizumab, we saw improvements in progression-free survival and overall survival, albeit minimal. I think the important thing was that we saw an increase in durable responses. With a disease that is so deadly when there’s progression, those durable responses become incredibly meaningful. And so this has really become the standard of care—chemotherapy plus atezolizumab in the frontline setting.

This is a regimen I’ve adopted as frontline therapy: carboplatin-etoposide plus atezolizumab. Now, I’ll point out that I don’t necessarily give atezolizumab to everybody with the first cycle. If someone is admitted to the hospital, I think it is fine to just start the chemotherapy and add in the atezolizumab when they’re in the outpatient setting as second-line therapy. I’ve also had situations of patients where we’ve considered whether or not to add in radiation—whether we’re going to treat them as limited stage or extensive stage—and they’re kind of on the fence between those where I’ve sometimes held the atezolizumab initially while we’re doing that initial determination. I’ll say that what we see with the curves within the IMpower133 study is the separation of those curves really ends up being later on. So I think it’s OK to not give the atezolizumab with that first cycle if there’s good reason for that, and just to add it in as quickly as you can, depending on the course of events

Transcript Edited for Clarity