New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
SELECT: A multicenter Phase II trial of adjuvant erlotinib for resected early-stage, EGFR-mutant NSCLC
2:58 minutes.
TRANSCRIPTION:
DR OXNARD: The SELECT trial was — mainly it was a feasibility study. It took any stage patient with an EGFR mutation. Key lessons learned is that if you insist they take full dose for 2 years, they’ll quit. But if you bring them down to a dose that doesn’t make them feel crummy, they’ll stick with it. I will point out that in the study you just described, 40% of the patients in the EGFR-mutant arm stopped therapy before 12 months. Again, it makes you feel crummy. But the drug works at 50 or 100 mg. Bring it down to a dose they can tolerate, they’ll stick with it. A second important point is that when you stop the drug, the risk of recurrence escalates. Okay? And so there was like minimal recurrence during the period on therapy and then a dramatic development of recurrences afterwards. In those patients, they could then re-receive erlotinib and re-respond, which they’re not necessarily resistant just because they had the adjuvant therapy for a bit. They could receive therapy again, respond again and gain benefit again. So the SELECT trial informs the design of the ALCHEMIST study in how we dose the therapy, how we encourage re-treatment down the line, but it still is a single-arm study of a relatively low-risk population. A lot of them were Stage I. In my practice, I am not routinely using adjuvant erlotinib or crizotinib. I believe in the need for the ALCHEMIST study, and I’m part of the leadership. But in the really, really high-risk patients, in the patients who are like Stage IIIB, I mean the patients who are just definitely going to recur, who had a terrible benefit from neoadjuvant therapy maybe, I have used adjuvant erlotinib, if it seems clear to me that their cancer is going to come back, toward the hope of that not being a devastating recurrence in the brain or in the bone, which is going to make them really unwell. DR LOVE: So Anne, agree or disagree? DR TSAO: So I definitely don’t use it in the adjuvant setting, for the reasons specified. I think there’s hopefully information that we’ll learn from ALCHEMIST, but my concern is that we don’t know the time duration we need to keep these patients on. That is still completely unknown. DR CARBONE: So I have strong opinions on this that aren’t reflected by some of the discussion we’ve had. I think overall survival is the only relevant endpoint in curable disease. And looking at PFS is a self-fulfilling prophesy in this situation that really what you — the purpose of adjuvant therapy is to eliminate micrometastatic clones of disease. And you would think that anyone who’s treated EGFR-mutated disease knows maximal response happens in 6 to 8 weeks after starting therapy. So I totally don’t buy that you’re helping these patients with 2 years of therapy, anything more than just suppressing preexisting metastatic disease. You’re not actually improving cure rates in these patients. |