FLAURA-2 and HARMONi Trial Readouts Reinforce Importance of ‘Divide and Conquer’ Approach to Lung Cancer Care at WCLC 2025

The International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC) concluded on Tuesday after 4 days of data-driven discussions on evolving treatment paradigms, emerging therapeutics, and critical advancements in lung cancer care.

During the meeting, OncLive® asked the following experts to spotlight the most important research and conclusions to come out of the meeting:

• Geoffrey Liu, MSc, MD, senior scientist, Princess Margaret Cancer Centre; professor, the Epidemiology Division, Dalla Lana School of Public Health, the University of Toronto
• Sandip P. Patel, MD, professor of medicine, the Department of Medicine, the University of California, San Diego (UCSD); medical oncologist, UCSD Moores Cancer Center
• Alexander Drilon, MD, thoracic medical oncologist, early drug development specialist, Memorial Sloan Kettering Cancer Center
• Eric K. Singhi, MD, assistant professor, the Department of General Oncology, the Division of Cancer Medicine and the Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
• Alexander I. Spira MD, PhD, FACP, FASCO, codirector, Virginia Cancer Specialists Research Institute; director, Thoracic and Phase I Program; clinical assistant professor, Johns Hopkins School of Medicine.
• Yang Xia, MD, PhD, associate professor, the Department of Respiratory Medicine; vice chair, the Department of Pulmonary Medicine, the Second Affiliated Hospital Zhejiang University School of Medicine

Top takeaways included highly-anticipated overall survival (OS) data from the phase 3 FLAURA2 trial (NCT04035486), which suggest a role for treatment intensification in EGFR-mutant non–small cell lung cancer (NSCLC); updates with the PD-L1/VEGF bispecific antibody ivonescimab (SMT112) from the phase 3 HARMONi trial (NCT06396065); and the meeting’s overarching focus on precision oncology for refining patient subgroups and applying targeted therapies in lung cancer care.

For those who missed the meeting in Barcelona, Spain, check out their unique perspectives and insights below!

Do Final OS Data From FLAURA2 Prompt a Shift Toward Intensified First-Line Therapy for Select Patients With EGFR-Mutant NSCLC?

Liu: Some of the latest trials of importance that are coming through [in lung cancer] are actually in the targeted sphere right now. At this meeting, we were very interested to see what the exact results of the FLAURA2 trial were. [FLAURA2] involves combination chemotherapy with osimertinib [Tagrisso] vs osimertinib [alone]. We've seen the OS data from [the phase 3] MARIPOSA trial [NCT04487080], which is the competing combination that could be used in the same frontline setting. It will be interesting to tease out the details here, because we still have to make a very important decision in the future: which of these combination regimens we would prefer to use in this setting?

Xia: [Data from] FLAURA2 eventually gave [us] the answer for whether chemotherapy plus a TKI is a preferred first-line option in EGFR-mutant advanced NSCLC. I still remember the progression-free survival [PFS] data being reported 2 years ago in Singapore at WCLC. The PFS striking PFS benefit was quite impressive. However, the data [shared this year] also showed significant and clinically meaningful OS benefits for the chemotherapy plus TKI [regimen] compared with a TKI alone in the first-line setting. I think [these data] will change our clinical practice in a short period of time."

Singhi: We had a really great set of presentations at the Presidential Symposium. For our patients with EGFR-positive disease, both in the first-line setting and beyond, there continues to be an unmet need due to disease progression on targeted therapy. The final [overall survival] update from FLAURA2 [showed] that the combination arm's median OS was improved by approximately 10 months.

A particular point that I found interesting from that presentation [reflects] a question I commonly get from patients in clinic: on average, how long are patients on chemotherapy? [After this presentation], I now have that data to bring back to patients: it was approximately 8.3 months. That's not to say that we shouldn't encourage our patients to continue to follow how the clinical trial was designed, which was to continue the pemetrexed for greater than 8 months. However, it is something that you can bring into the conversation if your patient has a question [about treatment duration].

Drilon: We saw the FLAURA2 OS data readout, and we did see divergence of the curves and a meaningful shift in the OS medians [with the combination]. [These results] underscore that, particularly for some patients, there is a role for treatment intensification in the EGFR-mutant landscape. What we're going to need to do is figure out with more sophistication which patients might really need the intensification, vs which patients may not necessarily need that type of escalation of therapy.

Is Ivonescimab the Next Frontier in Lung Cancer Treatment, or Are Further Data Still Needed?

Spira: This year, we [saw] data [with] ivonescimab reported. Ivonescimab [is a] PD-L1/VEGF bispecific antibody, [and it] has really come out of nowhere. It has caused a lot of turnover, interest, excitement, and questions in oncology. Now, a couple of these new bispecifics are being developed by other pharmaceutical companies as well. Everybody's really excited to see what's going to happen with this drug.

Singhi: We also [saw findings from] the HARMONi study [reported], which were somewhat unsatisfactory. We were hoping for more for our patients [to experience benefit], particularly those who experienced disease progression. However, we saw that the VEGF/PD-1 combination didn't provide the benefit we were hoping for with regard to a prolonged response that was meaningful for patients. More details are yet to come with that drug, but at this time, [the data are] not yet practice-changing.

How Does Precision Oncology Reflect the “Divide and Conquer” Approach to Managing Lung Cancer Subtypes?

Patel: The theme [of WCLC 2025] has been precision oncology. [This comes in the form of targeted] treatments and combination therapies, [as well as] using molecular diagnostics to refine patient subgroups, and then trying to treat them with more specific therapies. I'm excited to see the potential for new therapeutic options for our patients, which could include practice-changing studies and updates that look at OS showing the benefit for patients with EGFR-mutated lung cancer, as well as what to avoid in those patient populations.

This has been a meeting about coming together, and the way we've come together to try to fight lung cancers. It's a strategy of “divide and conquer”: dividing up lung cancer into EGFR-, ALK-, ROS1-, PD-L1-sensitive types [of lung cancer], addressing those scientifically, and then looking at resistance within those lanes as one. When we look at this meeting, we see a very concerted effort to do this as a global community, which is the only way we're going to solve this problem because [lung cancer is] not just one disease.

To check out more of OncLive’s coverage from the meeting, click here!