Checkpoint Inhibitors in Second and Third-line



Naiyer A. Rizvi, MD: That’s a good dovetail into talking about our first experiences with immunotherapy [I/O] in small cell lung cancer [SCLC]. The approval of nivolumab. I think that the last approval in small cell lung cancer before that was topotecan, so it’s been some time since there’s been some progress with immunotherapy. Surprisingly it was actually a little late to develop. Immunotherapy was a little late to develop in small cell lung cancer because people were a little dissuaded by the sick-patient population, them being largely PD-L1 [programmed death-ligand 1]—negative. Jamie, maybe you can talk us through your experiences using NIVO [nivolumab] or PEMBRO [pembrolizumab], IPI-NIVO [ipilimumab-nivolumab]. Before the first-line approval, how were you using immunotherapy second or third line?

Jamie E. Chaft, MD: Interestingly, the experience here is not all that different from the non—small cell lung cancer experience [NSCLC], with the exception that the patients are sicker. What we see is a tremendous immunotherapy response signal in a minority of patients. And we struggle in the same way we have in other diseases with predictive biomarkers. But for our patients who are sick, particularly those with cytopenias in whom third-line chemotherapy is not appealing, the immunotherapy lends a very exciting option. And I have had some really nice responses, both to monotherapy and combinations, though the vast majority of patients unfortunately do progress.

Naiyer A. Rizvi, MD: Do you use single-agent NIVO [nivolumab]? Were you using IPI-NIVO [ipilimumab-nivolumab] combination? Were you use NIVO 1 [nivolumab], IPI [ipilimumab] 3 or NIVO [nivolumab] 3, IPI [ipilimumab] 1? What did you do? All of the above is probably the answer.

Jamie E. Chaft, MD: All of the above with the exception of IPI [ipilimumab] 3. My comfort zone was with a lesser dose of IPI [ipilimumab], so I did tend toward double therapy though with 1 mg/kg of ipilimumab.

Naiyer A. Rizvi, MD: Ticiana, what’s your experience in the second- and third-line settings? Were you using topotecan and then going to I/O [immuno-oncology] or were you going straight to I/O after first-line failure?

Ticiana Leal, MD: One of the things that happened is that even before the approval of nivolumab, NCCN [National Comprehensive Cancer Network] had actually included the option of using nivolumab or nivolumab plus ipilimumab in the second or third line and beyond. At that point, because we try to use everything but topotecan, I actually was using, prior to FDA approval, in select cases, nivolumab or NIVO [nivolumab] plus IPI [ipilimumab]. However, I would echo what Jamie has said in terms of the experience, the clinical experience with patients. I certainly think that when you use monotherapy it’s very well tolerated. For those patients—I’m going to call it indolent small cell—that almost behave like a non—small cell, I actually had good experiences because it was a well-tolerated treatment. And a small percentage of patients who did derive clinical benefit and had responses and durable responses as we’ve seen before.

My experience with NIVO-IPI [nivolumab-ipilimumab is that] I did try to use it as it was in CheckMate 032, but the toxicities in that setting were significantly higher than the benefit that I really wanted to see and that perhaps patients wanted to see. The NIVO-IPI [nivolumab-ipilimumab] combination as in CheckMate 032 was difficult to tolerate for patients. I didn’t use a whole lot of pembrolizumab at that point, but certainly after approval of NIVO [nivolumab] in third line, I have been following the FDA label now with approval of immunotherapy in frontline less and less. But I still try to use second-line irinotecan or paclitaxel and try to avoid topotecan, mainly because a lot of these patients just can’t handle the cytopenias with topotecan, and the benefit just doesn’t seem worth the toxicity when I talk about it with patients.

Transcript Edited for Clarity

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