In a complete dialogue of EGFR-mutant non-small cell lung most cancers on the American Society of Medical Oncology (ASCO) annual assembly, a variety of important developments had been highlighted, notably from the LAURA trial, which confirmed improved progression-free survival with osimertinib (Tagrisso) in sufferers with domestically superior illness.
MedPage As we speak introduced collectively three professional leaders within the area for a roundtable dialogue: Moderator Roy Herbst, MD, PhD, is joined by Anne Chiang, MD, PhD, and Sarah Goldberg, MD, MPH, all of Yale Most cancers Middle in New Haven, Connecticut. This third of 4 unique episodes delves into the LAURA trial’s affect and different promising EGFR-targeted therapies.
Click on right here to look at the opposite movies from this ASCO roundtable collection.
Following is a transcript of their remarks:
Herbst: OK, subsequent query. Let’s speak about EGFR. There was a plenary speak in EGFR, the LAURA trial, after which there have been a few research different methods to focus on EGFR. Let’s begin with the LAURA. Inform us about LAURA.
Goldberg: So LAURA was one of many trials that received the standing ovation on the plenary, and I feel that individuals had been actually — and I used to be additionally actually excited concerning the knowledge. So the LAURA trial is sufferers with domestically superior EGFR-mutant lung most cancers who bear chemoradiation, after which had been randomized to both obtain osimertinib or placebo. So this is similar inhabitants of sufferers that had been included within the PACIFIC trial, however we all know that these sufferers with EGFR mutations do not do very effectively with immune remedy, whether or not it is metastatic or in domestically superior illness.
So this was a very vital trial. I have been ready for the outcomes of this trial for years, and it was unbelievable to see the outcomes. I anticipated it to be a optimistic research based mostly on the advantage of osimertinib in stage IV and the profit within the ADAURA trial for resectable stage II and III. However this was actually unbelievable. The progression-free survival or the disease-free survival was considerably improved with the addition of osimertinib. And I feel what was actually eye-opening to me was how poorly individuals did on placebo. So chemoradiation alone for EGFR-mutant lung most cancers is simply actually fairly horrible. Most sufferers, the overwhelming majority of sufferers, progressed inside a couple of years or perhaps a few months with simply chemoradiation. So osimertinib actually improved the disease-free survival.
Herbst: Yeah, these had been stage IIIA, IIIB, IIIC.
Goldberg: That is proper.
Herbst: So a few of these sufferers had been fairly near metastatic illness.
Goldberg: I feel in all probability lots of them had metastatic illness, whether or not it was micrometastatic and we did not see it on imaging. I feel that is principally what it is telling us. And I suppose we all the time knew that about stage III illness since so lots of them recur. However I feel this was actually eye-opening to me that with out consolidation remedy, so many of those sufferers had been recurring and with osimertinib they had been doing significantly higher, though even so sufferers nonetheless there was development now, happily years later.
The opposite factor I simply wish to point out concerning the design of the trial, totally different from ADAURA the place sufferers received 3 years of adjuvant osimertinib. The decrease trial, the osimertinib, saved going so sufferers may very well be on it indefinitely, which there was a number of dialogue within the panel about whether or not that is applicable or not, however that is how the research was designed. In order that’s the best way the sufferers had been handled was they received indefinite.
Herbst: So what do you suppose Anne, new commonplace of care?
Chiang: I feel so. I feel so. I do suppose one of many factors that Dr. Sequist made within the dialogue is speaking to your affected person about remedy or not, and that we should be somewhat extra pragmatic that many of those sufferers do have micrometastatic illness. I feel that speaking to your affected person about indefinite remedy is one thing that — we have to introduce that idea. I feel that sufferers who’ve been on [osimertinib] for 3 years and tolerated, they are going to be pleased to proceed. Truthfully, they have been dwelling with it for 3 years and I feel they’d be extra anxious to cease.
Goldberg: Yeah, I agree. It is that stopping after 3 years is usually more durable than simply saying, OK, let’s simply preserve going. I truly fear concerning the monetary toxicity although generally that may actually be a problem that sufferers have these excessive copays. However I agree. I feel lots of instances individuals are pleased to remain on a drug that appears to be serving to. Their most cancers hasn’t returned and infrequently it’s extremely effectively tolerated.
Herbst: What about cell-free DNA and MRD [minimal residual disease]? Can that be used?
Chiang: Yeah. Effectively, truly it simply got here from the session from the ADAURA trial the place they checked out MRD and utilizing ctDNA [circulating tumor DNA] by way of often longitudinal monitoring of whether or not or not ctDNA was displaying up. And on this, it was fairly spectacular that within the placebo arm there have been much more purple dots indicating presence of ctDNA that weren’t there within the osimertinib arm. So I feel that that might be useful probably to deescalate.
The opposite a part of that that was notable to me was that a lot of the sufferers, or truly all the sufferers who progressed had been just about after they stopped their remedy. So inside the subsequent 12 months, all people progresses. So once more, supporting this concept of micrometastatic illness.
Herbst: No, completely. So there are additionally, Sarah, within the session you shared there have been a number of abstracts with amivantamab [Rybrevant] + lazertinib [Leclaza] and MARIPOSA updates. Inform us about that and the way that matches in, and subQ [subcutaneous] versus IV [intravenous].
Goldberg: Yeah, these had been some, I feel additionally different actually thrilling abstracts and shows that hopefully will change our follow within the subsequent couple of months to years.
So there was a research that was offered at ASCO this 12 months that I assumed was actually vital the place they in contrast subcutaneous to intravenous amivantamab. And that is actually vital as a result of IV amivantamab, which is what’s accredited proper now, has a very excessive fee of infusion-related reactions. I truly inform my sufferers they’re very more likely to get a response. Most frequently it is low-grade reactions and so they do OK with stopping, slowing the speed, supportive measures. However generally there are excessive grade reactions, however it’s positively difficult. The opposite factor is it takes hours to present the primary dose. It’s a must to give it on days 1 and a couple of. So IV amivantamab is basically difficult logistically. After which for the sufferers once they have a response.
However this research principally in contrast subcutaneous versus IV and confirmed that the charges of infusion reactions had been considerably decrease. It took 5 minutes versus one thing like 5 hours to present. And the scientific outcomes had been the identical and truly perhaps even somewhat higher with the subcutaneous kind, which I do not know that I can fairly clarify, however they weren’t inferior. They regarded the identical or perhaps even higher with subQ. So this isn’t accredited but, however I hope that it will likely be. After which perhaps that shall be an possibility to be used for our sufferers.
Herbst: Make it quite a bit simpler for sufferers by way of compliance and high quality of life.
Goldberg: I agree.
Herbst: OK. Is there the rest on the horizon, Sarah, for EGFR-mutant illness?
Goldberg: I feel what’s so vital on this house proper now is determining the very best first-line routine. So we have had first-line osimertinib for a number of years now, and I feel that that is actually the common follow is that we use that after we make a prognosis of metastatic EGFR lung most cancers.
However now there’s a couple of regimens that look probably higher. So the FLAURA2 routine, this wasn’t at ASCO, but it surely’s within the final 12 months or so. I feel this has actually emerged. FLAURA2 routine of chemotherapy, carboplatin plus pemetrexed, with osimertinib has an enchancment in progression-free survival. After which amivantamab plus lazertinib additionally improves progression-free survival in comparison with osimertinib. And the FLAURA2 routine is accredited. So these are potential choices for our sufferers.
I feel what the problem is is determining which sufferers want these regimens and who can get away with single-agent osimertinib. We already talked about how single-agent [osimertinib] is so tolerable, and a few sufferers do extremely effectively for years and years, however sadly some sufferers do not do as effectively and so they progress in a 12 months or two. And so attempting to determine which of these sufferers want the mix is so key and I hope that we will determine that out.
Herbst: Completely. It is so thrilling. We first began utilizing EGFR inhibitors in 1996. Mutations had been printed, I feel 2004, now 20 years later, we’re utilizing these greatest medicine earlier. Now we have correct approaches now in stage I, II, and III illness, ADAURA, and stage III chemoradiation, LAURA, we now have a neo-ADAURA happening in neoadjuvant. It simply is nice to have this. After which what about extrapolation to ALK or MET or RET? What do you suppose?
Goldberg: Yeah, I feel going again to the LAURA knowledge, I feel the profit with consolidation osimertinib after chemoradiation in stage III illness was so nice that I feel we perhaps can take into consideration extrapolating to different subsets. We do not have knowledge on this. Possibly in the future we’ll, I do not know. However I feel we will extrapolate to ALK and ROS1, perhaps RET.
We won’t do it to all the pieces as a result of I feel generally the medicine get considerably poisonous and likewise the profit even within the metastatic setting is decrease. So for instance, I would not extrapolate to KRAS, however I feel we will begin to consider extrapolating.
One of many different shows I am going to simply spotlight is that one in all our residents at Yale truly had a presentation yesterday within the mini oral session for early-stage domestically superior lung most cancers, a retrospective knowledge set of ALK-positive domestically superior illness sufferers, and principally consolidation ALK TKI [tyrosine kinase inhibitors] additionally regarded higher than both durvalumab [Imfinzi] or placebo or surveillance. So I feel we will begin to extrapolate from a few of these subsets based mostly on the decrease knowledge.
Herbst: Completely.
