MARIPOSA, LAURA, and SAVANNAH: Dr. Liu Weighs In on New Data in EGFR-Positive NSCLC

Stephen V. Liu, MD, of the Georgetown University School of Medicine and Georgetown’s Lombardi Comprehensive Cancer Center in Washington, DC, joined Lung Cancers Today to discuss key highlights from the European Lung Cancer Congress (ELCC), which took place in Paris, France.

The congress featured multiple practice-informing updates in non–small cell lung cancer (NSCLC), including the much-anticipated overall survival (OS) data from the phase 3 MARIPOSA trial, Dr. Liu said.

“What we saw at this meeting was the improvement in overall survival. We had a bit of a teaser from a press release, but here we see the concrete data. The projected improvement in median [overall survival] will be over a year,” he said. “We see Kaplan-Meier curves that split after 12 months and that OS hazard ratio of 0.75 certainly is meeting our bar for a clinically meaningful and statistically significant improvement in survival.”

Dr. Liu explained the nuances of the trial, which has been evaluating amivantamab plus lazertinib versus osimertinib as a first-line treatment for patients who have locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations. He also discussed the practical considerations involved with using the regimen of amivantamab plus lazertinib.

“This combination regimen does introduce infusions and does introduce more toxicity… but the COCOON study, a supportive care trial also presented at the ELCC, shows that different dermatologic interventions can reduce that dermatologic toxicity,” Dr. Liu said. “We know that we need to use prophylactic anticoagulation and that can help counter the venous thromboembolic events.”

He explained that although “one might look at all these supportive care medicines and say ‘It’s a much more complicated regimen to deliver,’” it’s important to recognize that “we use just as many supportive care medications when we’re delivering chemotherapy; it’s just that’s a regimen that we’ve become accustomed to over time.”

“It’s probably time that we start looking closer at this regimen for more, if not most of our patients,” Dr. Liu said of the MARIPOSA regimen.

However, he pointed to a critical unanswered question: “Will we see a similar or different survival benefit with the FLAURA2 regimen?”

“I think that could make the calculus a little bit more complicated,” Dr. Liu said. “But for now, we do have a regimen that improves survival, and I think, warrants discussion with all of our patients diagnosed with EGFR-positive lung cancer.”

Dr. Liu Weighs In on SAVANNAH and LAURA Data Presented at ELCC 2025

Beyond the MARIPOSA data, Dr. Liu also highlighted the primary results from the SAVANNAH trial, which were presented at ELCC 2025 by Myung-Ju Ahn, MD, PhD, of the Sungkyunkwan University School of Medicine. The trial evaluated the combination of savolitinib, which is an oral, potent, and highly selective MET tyrosine kinase inhibitor, and osimertinib.

During her presentation, Dr. Ahn explained that savolitinib plus osimertinib “demonstrated clinically meaningful and durable” responses in patients with EGFR-mutated advanced NSCLC and MET overexpression who had disease progression during first-line treatment with osimertinib.

It was an important trial, Dr. Liu explained, because resistance to osimertinib is a frequent challenge, and it’s critical to evaluate strategies to overcome mechanisms of resistance.

“For MET amplification, it depends on how you define that mechanism, but more and more, this is an actionable mechanism of resistance,” Dr. Liu said. “Although if we do shift more towards MARIPOSA in the front-line setting, this probably has less relevance because we don’t expect to see a lot of MET-mediated resistance if we’re using MARIPOSA.”

ELCC 2025 also featured critical updates on overall survival from the phase 3 LAURA trial, which were presented by Suresh S. Ramalingam, MD, of the Winship Cancer Institute at Emory University.

“While this study needs a little more time to mature, what we’re seeing early on is very encouraging,” Dr. Liu said. “We saw profound improvements in progression-free survival with the use of osimertinib after definitive chemoradiation. This is a setting where we try to cure patients with chemoradiation, but the data, looking at the control arm, tells us we do not cure very many patients at all with EGFR-mutated lung cancer using chemoradiation.”

During his ELCC presentation, Dr. Ramalingam explained that the overall survival analysis “demonstrates an improved favorable trend for overall survival benefit with osimertinib over placebo.” Dr. Liu weighed in on these early overall survival results and the potential implications.

“We are seeing those survival curves start to split, and one has to believe with this profound degree of PFS [progression-free survival] benefit, that it will translate to an overall survival benefit,” Dr. Liu said. “This is not a disease that we can wait to relapse or to recur, so this strategy does seem to be a winning one.”

Dr. Liu concluded by reflecting on the evolution of the therapeutic landscape for EGFR-positive NSCLC.

“Our treatments are getting more effective and more complicated,” he said, noting that these advances come from “a more sophisticated understanding [of] this disease space” and that there is now “a lot of excitement in that EGFR space” with “the promise of more changes to come.”