ASCO 2019 Lung Cancer Round Table: New Cancer Research: Important Results from Afatinib Trial

WEST: Let’s turn to another population that’s still early stage, and that is patients who have a driver mutation, in this case a EGFR mutation, who have undergone surgery. Doctor Chaft from Memorial Sloan-Kettering led a study that was in a few centers, a phase 2 study that looked at giving post-operative a Afatinib one of the second-generation EGFR inhibitors for either 3 or 24 months to patients with a resected…I believe it was stage 2 or 3, non-small cell lung cancer with an EGFR mutation.
The trial was designed to have over a hundred patients, but it closed early with really pretty low enrollment, and I think one of the other striking findings of the study was that most patients did not continue on it for more than a few months due to side effect issues and just overall lack of enthusiasm.
That said, it seemed to be a toward better relapse free survival in the patients who were on the longer duration of the Afatinib. No difference in survival, but this is a small early discontinuation of the study.
I think the main question I’m left with is, does this tell us anything about how you might treat or approach a patient with an identified driver mutation in the postoperative setting? We don’t have an overall survival benefit demonstrated yet, but we have a few studies that show what seems to be a delay in the relapse, improvement in relapse re-survival. Is that enough? Is Afatinib just too toxic or a poor choice, or what what kind of takeaway did you have from this? Charu can I start with you? CHARU: Sure, so you know I think it was a step in perhaps the right direction, but of course when the study was designed, Afatinib was one of the drugs that was our preferred agent, perhaps in some instances to use as an EGFR TKI. I think it mirrors some of the observations with Erlotinib, as in the selected trail that was presented and published earlier by Dr. Nate Pannell. I think it’s interesting to see the disease-free survival was slightly longer for the patients that received Afatinib for a full two years versus just three months, but again having said that I think we have much better tolerated TKIs. I don’t think Afatinib would be my first choice in going towards, you know, if I were to choose an EGRF TKI in this curable, curative intent setting. And secondly, I think we definitely should base our clinical decision-making on overall survival, not so much just on diseases free survival especially in the setting of curative intent therapy. WEST: How about you Ben, do you have a similar view? LEVY: I would agree with Charu, I think the big questions in this space are, what is the right drug and for how long? and I don’t think we’ve had those answers addressed definitively or had these questions are addressed or answers to these questions yet. As you mentioned in the adjuvant Afatinib study, only 50 percent of patients were able to actually complete therapy for two years and the drug is toxic we have trials though in this phase that I think will hopefully, answer this question.
We have the alchemist trial, looking at adjuvant erlotinib as well as crizotinib for ALK-rearranged lung cancer. We havee the adora trial too, for adjuvant osimertinib.
At this point in time, I’m not ready to use a TKI Afatinib based on disease rate survival I think we need overall survival. And we hopefully will have answers, I’m hopeful in the next five years, where we can really make decisions with the use of these drugs for these specific genotypes.
WEST: I agree, I am, I would really be disinclined to pursue an adjuvant treatment with known side of effects and undefined potential survival benefits.
I think that, for me personally, relapse-free survival is worth knowing about and has some value, but if it’s not doing anything more than postponing the relapse that would happen, I am reluctant at to have a whole bunch of people who may never have the cancer return, be subjected to the cost and toxicity issues of a treatment that we don’t have an endpoint for.
I think one of the other issues that of this was introduced by the whole design of this trail being three vs 24 months is, with adjuvant chemo, part of the, I would say, appeal of it is that it’s a limited time of treatment – it’s challenging, but it’s defined three months to hopefully
eradicate all of the disease and we don’t know if three months or or 24
months or more or less is is an optimal thing in targeted therapy setting.
I think that is a different ask really when you may be having people on this for a very long period of time. The other thing is that clearly the toxicities matter of all of our treatments certainly in the stage 3 or 4 setting, but when you move into a group of patients who may already be cured, I think that it’s really an issue to have them under take the toxicity issues potentially for long periods of time, of these therapies. You know rash and diarrhea are not trivial and definitely not in patients who may cured already.

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