Naiyer Rizvi, MD: Leora, I'm going to ask you a difficult question. You have a patient who comes in with a PD-L1 [programmed death-ligand 1 expression] of 90% and a TMB [tumor mutational burden] of 30 mutations per mega base, and you give 2 cycles of immunotherapy and they don't respond. Do you switch them to chemotherapy, or do you continue the immunotherapy [I/O]?

Leora Horn, MD, MSc: I think it depends on how they're not responding. If their scans look a little bit worse but they feel fine, I might give them a couple more cycles and see how they do. If they are feeling worse and looking worse, then I would switch them over to chemotherapy at that point. I was going to say before about what Josh was referring to and Jacob about a poor biomarker, I think it's important to remember that pembrolizumab is not the only drug. It's a good drug, and if it works, that's great, but it does not work in the majority of our patients. The long-term data from KEYNOTE-001 are showing us that in the PD-L1 greater than 50% group, 30 patients are alive at 5 years. That means it's working in about a third, maybe less, of our patients who are greater than 50%. And so, don't keep going with the drug if the patient looks worse, they feel worse. The drug is not working. Switch them over to chemotherapy, and I have a low threshold to do that.

Naiyer Rizvi, MD: Josh?

Joshua Bauml, MD: Yes, I completely agree. I know that many people are doing this grafting on the chemotherapy to the I/O, but it's really a data-free zone. I feel much more comfortable dropping the I/O when it is not working and giving chemotherapy.

Naiyer Rizvi, MD: I agree with what Leora was saying, if there are specific areas or problem areas that can be locally managed or irradiated, and allows you to continue with immunotherapy, perhaps getting some increased antigen release through radiation, it’s worth trying to continue the I/O alone but radiate the problem areas. Tim, do you want to comment on that?

Tim Kruser, MD: Yes, I agree with what you're stating. There was a phase II study presented at ASTRO [the American Society for Radiation Oncology annual meeting] in Chicago last year that looked at exactly that scenario, people progressing on immunotherapy who they gave SBRT [stereotactic body radiation therapy] to 1 lesion. It was out of the Yale Cancer Center group, and they noticed some responses in people who had been progressing on I/O as well as some prolonged stability of people who seemed to be already failing immunotherapy. So we tend to add in radiation if there's a lesion that's amenable.

Transcript Edited for Clarity