New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
RADIANT subset analysis: Benefits of adjuvant erlotinib in patients with EGFR-mutant NSCLC
4:18 minutes.
TRANSCRIPTION:
DR SPIGEL: So this is an important study I think many of us were involved in, that actually began almost 10 years ago. And the idea was pretty simple. Adjuvant chemotherapy had found its way into standard management of Stage IB through IIIA non-small cell lung cancer, and could we do better with a drug like erlotinib, which was now on the market? The important thing about the timing of when this trial started was erlotinib was not recognized as the definitive drug in EGFR mutation cancers. It was an emerging story but not considered to be the way this drug should be used in this trial. Patients on this trial had Stage IB to IIIA non-small cell lung cancer, both histologies. Patients were randomized 2:1 to erlotinib or placebo. They could have gotten chemotherapy or not — it was the doctor’s discretion. You had to have an EGFR-positive cancer to get on the study, so that could be either by IHC or by FISH. Mutation testing was not a requirement to get on this study. The trial sought to enroll about 1,000 patients — this was a global study — and the primary endpoint was disease-free survival. In short, this trial was a negative study. If you look at the overall patient population, the patients who were allowed to get on this study regardless of mutation status, the disease-free survival was identical whether you got erlotinib in the adjuvant setting for 2 years or you got placebo. Interestingly enough, about half of the patients on placebo had to come off the drug over time for compliance issues or decided to just stop taking it. And about two thirds of the patients came off erlotinib who were on the study because of toxicity issues. Now, because about 160 of the 1,000 patients were known to have EGFR mutations, an additional analysis, planned analysis, was performed. And this was presented by Dr Frances Shepherd actually in a poster, but Karen Kelly presented some of the main data from that subset analysis. So there were about 100 patients who had EGFR mutations who received erlotinib, and there were about 60 patients in this total who had received placebo. When you look at the disease-free survival in those subsets of patients, there appears to be a disease-free survival advantage for the patients who had EGFR mutations who received erlotinib, so about 100 patients, remember. The disease-free survival in that group was about — I apologize — was about double what it was in the placebo group. When you look at overall survival for the overall intent-to-treat population, the medians have not been reached. When you look at the overall survival for the EGFR subset, the medians have not been reached. So there is a signal here, a suggestion, that disease-free survival is improved with erlotinib in patients with EGFR mutations, but it did not reach statistical significance. And that is the crux of the debate that’s occurred since this trial has been presented. Do we have enough data now to say that there’s a strong signal, although not statistically significant, to justify standard use of this agent in the adjuvant setting, knowing that’s really the patient population of interest for this strategy? Or do we say, “No, that’s just not enough patients to say that this is positive”? And should we wait on a larger prospective, randomized study where patients, to get onto the trial, all patients have to have EGFR mutations? And that’s the subject of the ongoing NCI effort. DR LOVE: That’s the ALCHEMIST trial? DR SPIGEL: The ALCHEMIST trial. DR LOVE: And there is also an ALK end to that one also, with crizotinib? DR SPIGEL: Yes. I’m not involved in that trial, but my understanding actually is, as biomarkers emerge, they’ll be added in, and ALK is one of those. DR CARBONE: They’re adding in PD-L1 as well. DR LOVE: PD-L1. Wow! DR SPIGEL: And I don’t want to misspeak, but this informs our discussion. I was told that for that trial to complete and reach its primary endpoint and reach some form of conclusion could take somewhere around 9 years. DR LOVE: The ALCHEMIST trial? DR SPIGEL: The ALCHEMIST trial for the EGFR — DR LANGER: At least for those 2 cohorts. DR SPIGEL: Yes, because they’re relatively rare. DR CARBONE: Adjuvant therapy endpoints are always long in coming. |