Balazs Halmos, MD, examines how clinicians can choose among emerging targeted treatment options for advanced EGFR-mutated lung cancer when direct head-to-head comparisons are not available. He discusses how efficacy data from FLAURA2 and MARIPOSA should be weighed alongside differences in toxicity, patient comorbidities, treatment burden, and the practical realities of delivering therapy in routine practice. He highlights the importance of shared decision making as clinicians consider options such as chemotherapy plus osimertinib and amivantamab-lazertinib for individual patients. Dr. Halmos emphasizes the need for additional real-world evidence, biomarker data, and sequencing studies to better define which patients are most likely to benefit from each strategy and how these therapies should be used over the course of treatment.
Transcript:
Dr. Halmos: I’m Balazs Halmos, medical oncologist from Montefiore Einstein Comprehensive Cancer Center from the Bronx, New York.
When direct head to head trials are unavailable, what evidence should clinicians prioritize when choosing among targeted treatment options?
Dr. Halmos: Well, of course, in between FLAURA2 and MARIPOSA, we have two excellent combination regimens, and they are now preferred for our patients with advanced EGFR-mutated lung cancer as compared to single-agent osimertinib. But we do not have comparisons between chemo-osimertinib versus amivantamab-lezertinib.
The reality is that in the next couple of years, we will need to learn to be able to administer either of these regimens to our patients in the safest possible manner. And we also need to learn as a larger community, are there particular patient profiles, you know, where one regimen might be superior to the other?
We don’t know that yet. But for example, for patients who are not great chemotherapy candidates due to kidney dysfunction, hematological issues, for example, or elderly age, for example, the subcutaneous amivantamab-lezertinib regimen provides an excellent alternative. So nice to have multiple choices.
Both of them seem about the same when it comes to efficacy. They have different adverse event profiles. We should discuss both of them with our patients and through shared decision-making, then deliver the regimen chosen in the optimal possible way.
As targeted therapies move into routine care, how should clinicians balance efficacy data with tolerability and the practical realities of treatment delivery when deciding what is right for a patient, particularly outside a major academic center?
Dr. Halmos: Targeted therapy, biomarker-driven cancer care has been around now for 20 years. But year by year, we’re seeing refinement, improvement in terms of have you offered this treatment to our patients? Have we been extending life expectancy, potentially offering chances of cure in earlier-stage settings?
So the big shift, of course, we’ve seen is the potential use of combinations, more intensified regimens, in terms of EGFR-mutated lung cancer. This is the chemo osimertinib and nivolumab versus lazertinib combination to be used. There are major advances, you know, but some new learnings for the clinician, and this is where fortunately with the COPERNICUS data now here, we can tell for sure that with sub-Q event and appropriate proactive preventive measures, we can make the patient experience just so much better for our patients so they can benefit now from combination targeted therapy and EGFR TKI and the combination EGFR bispecific antibody for extended periods of time, transforming the biology, transforming the outlook of patients with EGFR-mutated lung cancer, but also improving the patient experience, quality of life at the same time, two very important goals that now hopefully we’ll be able to achieve.
What evidence would you like to see on sequencing and real-world tolerability before these treatment choices become clearer?
Dr. Halmos: The treatment choices are here, so luckily we’re able to use them. But in terms of sequencing, what’s the first choice for a particular patient, we definitely need to learn a lot. So real world studies such as COPERNICUS are hopefully allowing us to understand the actual experience for patients in clinic, and thereby helping us optimize treatment choices for our patients.
But we need to learn a lot more in terms of baseline biomarker status, baseline clinical characteristics, acquired resistance mechanisms as to coming up with optimal sequencing choices. Good news is that we have more and more options now for our patients, not just in the second-, but also in the third-line setting.
So we’re moving on as a field, advancing the options for our patients in clinic. Challenging for the community oncologist or the academic oncologist alike, to be honest, with all the rich list of options. But we need to be here to learn together as a community so our patients can continue to get better and better.
