Investigator Perspectives on Emerging Concepts in the Management of Genitourinary CancersAnti-PD-1 and CTLA-4 combinations
1:29 minutes.
TRANSCRIPTION:
DR DRAKE: It’s always better than either of the drugs alone. In some tumor types, particularly melanoma, it looks like it’s a lot better, bordering on synergistic, actually. In kidney cancer, it’s better, actually. The Phase II data that my colleague Dr Hammers presented previously really show that the response rate goes from about 25% to about 40% or 45%. So that’s a lot more than PD-1 alone, but it’s not really the synergistic effect that you see in melanoma. Nevertheless, the combination has never been worse than either drug alone. The price you pay, of course, is increased toxicity. So whereas PD-1 is really quite well tolerated, PD-1 blockade has an adverse event rate of Grade 3/4 adverse events probably in the 15% range; CTLA-4 a little higher, maybe 20% to 25%. When you give them together, then you see a higher incidence of autoimmune events like colitis, sometimes pneumonitis and dermatitis. When we first started doing this, this was a big problem, right? Patients would have this sudden onset of adverse events. But now that we and other folks who do this are more used to it, the prompt initiation of immunosuppressive therapies, particularly steroids at first, then moving on if that’s not working, really has made it so most of these events don’t progress to that Grade 3/4 any more. So we’re able to catch them and treat them a little bit earlier, making these regimens that are actually practical that can be done in the clinic. |