Outlining Emergent Research in the EGFR-Mutated Lung Cancer Space

Treatment for EGFR-mutated lung cancer has dramatically changed in recent years with the development and emergence of EGFR inhibitors, according to Girindra Raval, MD.

Raval, an associate professor of the Department of Medicine: Hematology and Oncology at the Medical College of Georgia at Augusta University, discussed the evolution of treatment strategies for patients with EGFR-mutated lung cancers as well as emerging therapies that might appear promising for this population.

He began by touching upon the development of first-generation EGFR inhibitors, including erlotinib (Tarceva), gefitinib (Iressa), and osimertinib (Tagrisso), the latter of which was assessed in the phase 3 FLAURA trial (NCT02296125) among patients with metastatic disease.¹ Moreover, he suggested that positive data emerged from the phase 3 FLAURA2 trial (NCT04035486), which assessed osimertinib in combination with chemotherapy in the same setting.² Furthermore, he highlighted data from the phase 3 MARIPOSA trial (NCT04487080), which assessed amivantamab-vmjw (Rybrevant) and lazertinib (Lazcluze), as well as multiple TROPION-Lung studies evaluating datopotamab deruxtecan-dlnk (dato-DXd; Datroway) in patients with metastatic EGFR-mutated disease.^{3, 4}

Raval then touched upon trials in patients with early-stage disease, which included the phase 3 NeoADAURA (NCT04351555) and ADAURA trials (NCT02511106), which assessed osimertinib in the neoadjuvant and adjuvant settings, respectively.^5,6 Finally, he highlighted the phase 3 LAURA trial (NCT03521154), which examined osimertinib plus chemoradiation in an early-stage population.⁷

Transcript:

The landscape of EGFR-mutated NSCLC—or adenocarcinoma, specifically—has evolved significantly over the last few years. We are seeing the whole evolution start from first-generation EGFR inhibitors [like] erlotinib and gefitinib to the more recent osimertinib, which was [assessed in the] FLAURA trial for the metastatic setting. We are also now seeing the FLAURA2 data, which is combining osimertinib with chemotherapy.

There are the MARIPOSA data, which is combining amivantamab with lazertinib. Recently, there were data about datopotamab deruxtecan based on the TROPION-Lung studies in that same space, which is another tool that we now have for treatment of EGFR-mutated lung cancer in the metastatic setting. Now, this is on the metastatic side.

On the early-stage cancer side, we are awaiting results of the NeoADAURA trial in the neoadjuvant setting. We have the results of the ADAURA trial, which showed an overall survival benefit in the adjuvant setting, and we have results of the LAURA study, which showed efficacy of osimertinib after chemoradiation. A lot has happened in that space, and many trials are still ongoing. We have trials that we will talk about, hopefully, on where the field can go to eventually, but it is an exciting time, and a lot of things have moved in that space.

References

1. Soria J-C, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non–small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. doi:10.1056/NEJMoa1713137
2. Jänne PA, Planchard D, Kobayashi K, et al. Survival with osimertinib plus chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. Published October 17, 2025. doi:10.1056/NEJMoa2510308
3. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. News release. FDA. June 23, 2025. Accessed December 2, 2025. https://tinyurl.com/mvtyhnjf
4. Yang J, Lu S, Hayashi H, et al. Overall survival with amivantamab–lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693. doi:10.1056/NEJMoa2503001
5. He J, Tsuboi M, Weder W, et al. Neoadjuvant osimertinib for resectable EGFR-mutated non–small cell lung cancer. J Clin Oncol. 2025;43(26):2875-2887. doi:10.1200/JCO-25-00883
6. Wu Y-L, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non–small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. doi:10.1056/NEJMoa2027071
7. Lu S, Kato T, Dong X, et al. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597. doi:10.1056/NEJMoa2402614