Tagrisso has ushered in a brand new period of take care of sufferers with superior EGFR+ non-small cell lung most cancers, in accordance with Dr. Suresh Ramalingam.
Therapy with osimertinib (Tagrisso), as seen within the section 3 LAURA trial, has emphasised the agent as a brand new normal of take care of sufferers with unresectable, regionally superior EGFR-mutated non-small cell lung most cancers (NSCLC) primarily based on key survival finish level enhancements, in accordance with Dr. Suresh Ramalingam, a medical oncologist and govt director of Winship Most cancers Institute of Emory College.
To additional focus on this subject, Ramalingam sat down for a Q&A-style interview with CURE the place he highlighted the notable findings from the LAURA trial for sufferers with NSCLC.
“Whereas we’ve good remedies now and nonetheless have work to do, our present place provides rather more hope to sufferers than the place we have been 5 to 10 years in the past,” he defined.
Moreover, within the interview, Ramalingam additionally defined how Tagrisso is ushering in a wave of latest therapeutic approaches for sufferers inside this inhabitants, and what new and distinctive uncomfortable side effects are anticipated to come back with the remedy.
Ramalingam additionally serves because the affiliate vp for most cancers of Woodruff Well being Sciences Heart and holds the Roberto C. Goizueta Distinguished Chair for Most cancers Analysis. Just lately, in Might of 2025, Ramalingam was additionally listed on the TIME100 Well being 2025 checklist for his contributions to lung most cancers analysis.
CURE: To begin, are you able to go over the LAURA trial. What was the rationale for this analysis?
Ramalingam: The LAURA trial was carried out particularly to reply an vital query: For sufferers with stage 3 lung most cancers whose most cancers can’t be eliminated by surgical procedure, we at the moment use chemotherapy and radiation as an ordinary of care. Extra not too long ago, we’ve added immunotherapy to that remedy paradigm. Nevertheless, we have realized over the previous few years that for sufferers who’ve an EGFR mutation, immunotherapy will not be very efficient. However, concentrating on the EGFR by utilizing a drug like Tagrisso is extremely efficient. So, we needed to see whether or not, after chemotherapy and radiation, giving Tagrisso to sufferers with an EGFR mutation would end in higher outcomes.
Stage 3 lung most cancers is recognized in roughly 25% to 30% of sufferers with lung most cancers. Amongst these with stage 3, a small subset of sufferers can endure surgical procedure. For the others, as a result of the tumor is superior or they’ve many lymph nodes concerned, surgical procedure doesn’t assist them, and chemotherapy and radiation are used. We check with this as unresectable, regionally superior stage 3 NSCLC. It was for this explicit affected person inhabitants that the LAURA examine was carried out.
What latest findings have been shared relating to the LAURA trial?
A couple of yr in the past, we introduced the primary outcomes of the LAURA examine. When evaluating the usage of Tagrisso versus placebo after sufferers had accomplished chemotherapy and radiation, we noticed a major enchancment in progression-free survival. For example, within the progression-free survival information, sufferers handled with Tagrisso had almost 39 months the place the most cancers remained below management, in comparison with solely about 5 and a half months within the management group (sufferers who didn’t obtain Tagrisso). This was a big, statistically important, and clinically very significant distinction, and these outcomes shaped the idea for the FDA’s approval of Tagrisso on this setting. So, it’s now an FDA-approved drug for unresectable, regionally superior NSCLC.
What we reported not too long ago are some extra information on the affect of Tagrisso remedy on affected person general survival. This end result continues to be not mature; it’ll take us a pair extra years earlier than we absolutely perceive its affect. Nevertheless, at this preliminary look, we see a really favorable pattern in the direction of enchancment in survival for sufferers handled with Tagrisso. General survival is clearly one of many key endpoints. Earlier, we confirmed that Tagrisso prolongs the time the most cancers stays below management. So as to add that profit with a possible enchancment in survival makes it much more significant for sufferers with regionally superior NSCLC. So, that is the newest replace: a really encouraging survival pattern. After we reported the primary survival outcomes final yr, we noticed a positive pattern. This yr, with extra follow-up, that pattern seems to be much more optimistic.
The LAURA trial demonstrated an improved general survival pattern in sufferers with unresectable Stage III EGFR-mutated NSCLC. What’s significance of those findings inside the present remedy panorama?
Till now, and previous to the latest FDA approval, the usual remedy for sufferers with regionally superior, unresectable stage 3 lung most cancers, even these with an EGFR mutation, consisted of chemotherapy and radiation. Whereas some physicians used immunotherapy, we have noticed that immunotherapy doesn’t provide a major profit on this particular affected person group.
With the outcomes of this trial, we will now use Tagrisso after sufferers have accomplished chemotherapy and radiation, offered they’ve derived some profit from the preliminary mixed remedy. This remedy is now FDA-approved within the U.S. and is being included into routine follow. I think it is going to be step by step adopted in follow in lots of different elements of the world as effectively.
We have additionally seen a Chinese language drug, which has some similarities to Tagrisso, being examined within the stage 3 inhabitants, very like our examine. These outcomes additionally confirmed favorable outcomes, clearly suggesting that utilizing an EGFR inhibitor on this explicit setting is clinically significant.
Interstitial lung illness and pneumonitis have been noticed in over half of sufferers handled with Tagrisso within the LAURA examine. What concerns ought to oncologists bear in mind relating to danger administration and affected person choice?
One of many distinctive facets of the stage 3 illness affected person inhabitants is that these sufferers are handled with chemotherapy and radiation. A typical aspect impact of radiation is pneumonitis, or lung irritation. When Tagrisso is added to this routine, a priority arose about whether or not it could worsen this aspect impact.
The findings of the LAURA examine have been reassuring on this regard. Within the affected person inhabitants that acquired each placebo and Tagrisso, the commonest aspect impact was radiation pneumonitis, even with Tagrisso publicity. Whereas there have been numerically barely extra instances of radiation pneumonitis reported within the Tagrisso group, they have been comparatively delicate. None have been extreme sufficient to essentially change how we take into consideration the position of Tagrisso on this setting.
So, the important thing takeaway is that radiation pneumonitis can happen after chemotherapy and radiation. Physicians and sufferers want to pay attention to this. If sufferers develop signs like worsening shortness of breath, elevated cough, or fever, they should report it to their doctor. In most situations, these signs may be simply handled with a brief course of steroids, and the signs ought to enhance. The truth is, within the LAURA examine, after we needed to interrupt remedy with Tagrisso, we have been capable of resume it in a excessive majority of sufferers after their signs improved.
Tagrisso is more and more positioned as a spine remedy throughout a number of settings in EGFR-mutated NSCLC. How do the LAURA findings help this position, notably in earlier-stage, unresectable illness?
In metastatic NSCLC, or stage 4 NSCLC, Tagrisso is now the popular first-line remedy. Some newer research present that combining Tagrisso with chemotherapy can enhance outcomes. There’s additionally one other routine that features Lazcluze (lazertinib), an Tagrisso-like drug, with one other drug known as Rybrevant (amivantamab-vmjw), which has proven improved survival.
Whereas there are some choices obtainable, all of them depend on the truth that a third-generation drug like Tagrisso is the mainstay of remedy.
Now, about three or 4 years in the past, we realized that Tagrisso additionally improves survival for sufferers with early-stage lung most cancers who endure surgical resection. So, it’s now the usual of care in what we name the adjuvant remedy setting. The one group the place we weren’t clear was these sufferers who didn’t have stage 4 illness and didn’t have surgically operable illness — the unresectable affected person inhabitants. That’s precisely the group the LAURA examine evaluated.
So, Tagrisso is now mainly relevant for virtually each stage of NSCLC, maybe apart from stage 1A, the place it’s nonetheless being studied. You’re appropriate in your reference that that is now the mainstay of remedy for EGFR-mutated sufferers with lung most cancers in the US.
What extra information from the LAURA trial’s closing evaluation might be most crucial to additional validate Tagrisso position on this setting?
We’re clearly all in favour of discovering out the last word affect on affected person lifespan from utilizing this type of remedy. Our objective is for sufferers to dwell longer, dwell higher, and dwell effectively. When the LAURA examine outcomes are mature, we could have a solution to that query. As I discussed earlier, the developments we have seen up to now are encouraging.
We’re additionally all in favour of different biomarkers. For instance, can we use peripheral blood and sequence tumor DNA from the peripheral blood to find out who wants remedy and who might not? These kinds of questions are being addressed by ongoing research utilizing samples collected from sufferers who participated within the LAURA trial. We’re additionally exploring different research to see if we will use Tagrisso earlier than chemotherapy and radiation to attempt to enhance the affect of this drug on this illness. All of those are ongoing questions, and we anticipate finding out the solutions within the upcoming months and years.
Wanting forward, how do you see the outcomes of LAURA influencing ongoing or future medical trials geared toward optimizing the remedy of EGFR-mutated NSCLC, particularly within the regionally superior setting?
I would wish to make two key factors. First, we all know there are extremely efficient therapies for sufferers with EGFR-mutated lung most cancers, whether or not it is stage 1b, 2, 3, or 4. Nevertheless, you will not know you probably have an EGFR mutation except it is examined. Subsequently, it is completely important that sufferers with NSCLC endure molecular testing. This permits us to know the particular molecular traits of their most cancers, so we will implement probably the most acceptable remedy. It may very well be EGFR, ALK, or one thing else. The significance of testing is a vital message I need to convey to our viewers.
Second, particularly relating to regionally superior, NSCLC: when lung most cancers is recognized, it brings a whole lot of stress. Sufferers are attempting to study their analysis and varied remedy choices. For these with an EGFR mutation, getting access to these efficient therapies — which supply wonderful efficacy and hopefully fewer uncomfortable side effects — gives important reassurance as they start their remedy journey.
Whereas we’ve good remedies now and nonetheless have work to do, our present place provides rather more hope to sufferers than the place we have been 5 to 10 years in the past.
Transcript has been edited for readability and conciseness.
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