New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
A 62-year-old man with EGFR-mutant, advanced NSCLC treated on study with AZD9291 after disease progression on erlotinib
3:31 minutes.
TRANSCRIPTION:
DR OXNARD: This was a 62-year-old never smoker. He’s a retired firefighter. He presented initially with pleural metastases, Exon 19 deletion in EGFR. And he started erlotinib and had a nice response lasting about a year. As his tumor started to grow again, I looked for clinical trial options and ended up doing a resistance biopsy, which showed T790M, and he screened and started on the AURA trial of AZD9291. He had a brief washout, as all these patients do, 7, 8 days before going onto the new drug. And during that time, his symptoms of shortness of breath and cough began to escalate. He needed more oxycodone. He was up to 40 mg of oxycodone a day, or so, to manage these. When he started AZD9291, rapidly his cough and shortness of breath resolved. He actually presented for his week 1 follow-up visit with symptoms of sweats and diarrhea and had gone into rapid opiate withdrawal because he suddenly didn’t need the oxycodone at all. He’s had a really dramatic response and feels great. And I think the important point is, whereas he had rash and diarrhea on the erlotinib, he does not have any skin toxicity or diarrhea on the new drug. DR LOVE: And how long has he been on the drug? DR OXNARD: He’s now been on it for 6 months or so. DR LOVE: And any tolerability issues at all? DR OXNARD: No. He feels well. I mean, most of the patients I’ve seen definitely enjoy being on this drug better than on the initial EGFR TKI because of minimal EGFR-related side effects. He’s had no toxicity. DR LOVE: As he was deteriorating off erlotinib, did you think about chemo? DR OXNARD: I mean, it was during the washout. We had our sights set on the new drug, and so it was very clear what the strategy would be. But whereas we don’t necessarily see a dramatic flare leading to hospitalization, I definitely know that these washouts can lead to some deterioration, and large washouts can be a problem for patients. DR TSAO: One of the issues with AZD9291 that I’ve run into is QTc prolongation. So I’ve had to be really careful with that. I’ve had 2 patients, back to back in a row, who have had that issue. DR CARBONE: Just a comment about the QTc prolongation. I always am concerned about a laboratory number that doesn’t translate to any clinical reality. In the early days of paclitaxel, they were worried about bradycardia. And we had to do serial EKGs, follow their heart rate. And now you just give it and they go home and it’s not a problem. Do you think the QTc prolongation is something that needs to be monitored closely in practice, or is this just something that the FDA and bean counters like to look at? Is this a clinical problem? DR LOVE: Do you think that — you held the drug. Right? DR TSAO: Yes. DR LOVE: Do you think that — I mean, that’s a trial situation. But are you saying that maybe there’s — DR CARBONE: In the setting of metastatic lung cancer, a 0.2% risk of a cardiac event is probably acceptable. DR TSAO: Watching that QTc widen in front of me, though, I was not going to risk it. DR SPIGEL: Yes. It’s really been nononcologic drugs that had to come off the market because of this issue. And it’s made every drug development plan complicated because of this. I agree with you wholeheartedly. |