New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
Follow-up of the 35-year-old woman who was determined to have ALK-rearranged non-small cell lung cancer (NSCLC) and received crizotinib
3:35 minutes.
TRANSCRIPTION:
DR LANGER: So she’s put on crizotinib. She actually didn’t do so well with it initially, had a fair amount of nausea, although with dose adjustments and more aggressive antiemetics she felt better. Within a month she was off oxygen, absolutely no pain, back to work, amazing radiographic response, at least 80% to 90% shrinkage in this thick pleural rind. DR LOVE: Any tolerability issues with the crizotinib? Did she have that visual stuff? DR LANGER: Not once. Once she was out and about, off oxygen and pain free, she was feeling much better. To some extent, her GI issues may have been related to her narcotics. Unfortunately, her response was relatively short lived, which may be a bit atypical compared to other patients. But within about 5 months, she had developed some pain in the scapular area. She had lytic disease. It wasn’t clear if it was a separate hematogenous metastasis, perhaps direct bony invasion at T2-T3. She received some palliative radiation, felt better transiently and then developed more global progressive disease within the lung and the pleura. DR LOVE: So Dave, what would you be thinking about at this point? DR SPIGEL: It’s off study. I think ceritinib is a clear available option for everybody. And then it’s amazing the number of alternatives that are in trials now, that are available, these so-called next-generation agents. And they all look to be active. I think what’s a challenge for all of us, I mean, we have a chance to interact with patients like this, but it’s not uncommon for me to engage some of my colleagues in the community who say they’ve never managed a patient on crizotinib. And so you get a sense that they don’t really understand when these drugs are effective, when they’re not and then how ceritinib would play a role. That such a rare thing for most oncologists in the community. We spend a lot of time talking about these things, but you wonder about how common a clinical problem that will be for most doctors. DR LOVE: Do you think that that translates to these people should go to tertiary care centers? DR SPIGEL: I hate to say that when you have 2 fantastic drugs — maybe some of the best drugs we’ve ever seen in oncology — available everywhere in the US now. So you hope doctors are doing the testing and get experience with these drugs. But I do think for resistant patients, a lot of our patients have complicated situations. It’s probably worth getting an opinion at a center that has a little bit more experience. DR LOVE: So Corey, what happened to her? DR LANGER: Off study, I certainly would have chosen ceritinib, but we have an in-house trial, actually, an international Phase I, now Phase II trial of the Ariad compound AP26113. And we enrolled her on that. Unfortunately, within 3 days of the scheduled washout, she developed the most dramatic tumor flare I’ve ever seen. She went from out and about to just profound disease progression. She was in the ICU on a morphine drip and high-flow nasal cannula oxygen, really looking like she was going to die. And I begged the company, realizing that her performance status prior to the withdrawal of the crizotinib was still acceptable for the study. I received special dispensation. We started her on AP26113, and within a week, just like with crizotinib, she was much better. She was off oxygen. Within a month, off pain medicines and back to work and, as of 7 months later, about a 95% partial response. |