Evolving Approaches in Small Cell Lung Cancer - Episode 9

SCLC: Rechallenging With Chemotherapy + I/O

, , , ,

Anne Chiang, MD, PhD, renowned expert in thoracic oncology, guides a discussion on whether to rechallenge with chemotherapy + I/O after progression of small cell lung cancer.

Hossein Borghaei, DO, MS: Is it fair to say that in this panel, we still think there’s a patient population, although rare, who might benefit from exposure to I/O [immunotherapy] post-progression? Anne, would you say that since we’re using chemotherapy-I/O up front, there isn’t much of a role for rechallenging with I/O at progression after lurbinectedin and paclitaxel? In your mind, is there a role for an I/O agent?

Anne Chiang, MD, PhD: We can look to other cancer types for some guidance here. If you look at the melanoma or renal cell fields, there are some data that you can salvage patients who progress on I/O single agent with combination therapies.

Hossein Borghaei, DO, MS: But Anne, that’s not small cell [lung cancer]. That’s melanoma. Specifically in small cell, how do you feel about going back to a checkpoint inhibitor?

Anne Chiang, MD, PhD: Learning from other tumor types can help us. But for small cell, it may be that we haven’t given up on combination therapy or even single-agent therapy later on. I don’t think we know enough. If you look at clinical trials, we have all sorts of combination approaches, where hopefully one of them will nab the golden ring. But there may be a signal, perhaps with an anti–CTLA-4 combination with anti–PD-L1. Even for going back to a single agent after chemotherapy, this is something that should be tested and may potentially have benefit, so I’m optimistic.

Hossein Borghaei, DO, MS: Sorry for interrupting you. I wanted you to say a little more about the rationale for your ipilimumab-nivolumab study. Is that specifically post–chemotherapy-I/O or is it post–other lines of therapy?

Anne Chiang, MD, PhD: Our IIT [investigator-initiated trial] for ipilimumab-nivolumab is for relapsed small cell lung cancer, and it can be either on maintenance or further down the line. I don’t think we’re picky. If our patients have good performance status and they’re able to go on a trial so that we can look at what’s happening in a pretreatment and week-4 biopsy—we’ve gotten about a dozen of these paired biopsies to date that are really interesting—we can learn from that.

Hossein Borghaei, DO, MS: That’s great.

Stephen Liu, MD: You’ve got to hope that there’s some role for future immunotherapy. We tend to be optimists. In the lung cancer field, you have to be. When we look at immunotherapy vs other cytotoxic agents, we’ll see other drugs coming along, but the benefit is transient with cytotoxic agents. Immunotherapy as a class is so appealing to patients and oncologists because one of the tenets of immunotherapy is that long-term benefit and the potential for meaningful, durable long-term survival. It may be not going back to the exact same way you gave immunotherapy, but could there be some other synergy, attacking the microenvironment at the same time, or some way to unleash that immune response? We have to keep chasing that.

Anne Chiang, MD, PhD: If I could add one more thing to that: immunotherapy is not a homogeneous class. If a PD-1 inhibitor doesn’t work, then maybe a Siglec-15 inhibitor, which is not expressed on the same cells, could be very useful. There are going to be a lot of tools we can use to harness our immune system.

Hossein Borghaei, DO, MS: I’m really interested in your ipilimumab-nivolumab idea. That’s something that should be explored in patients who have evidence of disease progression, so I’m glad somebody’s doing that study. I’m looking forward to it.