New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
An 80-year-old woman with advanced, HER2-mutant nonsquamous NSCLC receives neratinib/temsirolimus on a clinical trial
3:07 minutes.
TRANSCRIPTION:
DR CARBONE: So this is an 80-year-old woman, never smoker. When I first saw her, she looked at least 20 years younger. She looked great. But she developed pneumonia in 2011 that really didn’t clear and was ultimately found to be lung cancer caused. And she had a surgery for this lung cancer, but about a year and a half later, she had multiple lung nodules found on surveillance CTs. And this was biopsied, and it was shown to be well-differentiated adenocarcinoma, EGFR- and ALK-, ROS-negative, but our next-gen analysis showed that HER2 was mutated. And she had not had any treatment for her advanced disease, but we had a trial where we had a HER2-targeted therapy, and that’s what we put her on. And this was a trial of neratinib/temsirolimus. And she had a near-complete response, in fact a complete response of the solid portion of her tumors. They looked more like GGOs, hard to measure, with very good tolerance, a little bit of diarrhea. Looks great now more than — I think she’s about 9 months out and still in complete response. DR LOVE: So Mark, what’s the spectrum of HER2 mutations that are seen, and what do we know in terms of responses to anti-HER therapy? DR KRIS: Yes. So HER2 in lung cancers is a fairly new phenomenon. Again, 10 years ago we wouldn’t have been discussing it, because the mutations weren’t discovered. In lung cancers, I think the most actionable HER2 abnormalities are mutations. Most of them are insertions in exon 20 of HER2. There are other mutations as well, that may be sensitizing. And there’s a thread through the number of reports in the literature that agents that target the HER2 kinase, afatinib, neratinib, lapatinib, dacomitinib, all of these agents have activity. But there are really very few prospective trials. Actually, I don’t think there are any prospective trials published yet. DR LOVE: What about trastuzumab, monoclonal antibodies, pertuzumab? DR KRIS: They have not comprehensively been tested in these patients. As it turns out, most of these patients are not HER2 protein overexpressed. They’re not 3+, which is standard in breast, nor are they amplified. So if that is going to be the criteria for benefit from trastuzumab, then the lung cancers do not meet that. |