The top content from the
Here are the highlights from WCLC 2025. Read all of the coverage of WCLC 2025
5. Current and Emerging Options for Uncommon EGFR- and Exon 20 Insertion–Mutated NSCLC
Nearly one-third of all EGFR-driven NSCLC cases were uncommon EGFR mutations like exon 20 insertions and compound variants, but treatments for these forms of NSCLC are still being developed. This article details a talk delivered by Aaron C. Tan, MBBS, PhD, FRACP, where he provided an overview of the different forms of therapeutic options for those with EGFR mutations and exon 20 insertion–mutated NSCLC. The current toolbox for EGFR mutations in NSCLC includes afatinib (Gilotrif; Boehringer Ingelheim), which was the first notable advance in uncommon EGFR mutations. Amivantamab (Rybrevant; Janssen Biotech) is a bispecific antibody that targets EGFR and MET and was granted initial approval by the FDA in May 2021. Both zipalertinib (TAS6417; Taiho Oncology and Cullinan Therapeutics) and furmonertinib (Ivesa; Allist) are among medications currently in the works to target this mutation of NSCLC.
4. PALOMA-2 Trial Supports SC Amivantamab Q4W as a Patient-Centered Alternative to IV Therapy
Amivantamab has previously been approved for use as an intravenous medication but could pose barriers to those who are not able to go to the hospital consistently to receive their dose. PALOMA-2 aimed to assess the efficacy of amivantamab delivered subcutaneously on a once-monthly every-4-week (Q4W) schedule. This was taken in combination with daily oral lazertinib. The study researchers found that the subcutaneous version of amivantamab had an objective response rate of 82% (95% CI, 71%-90%) by the investigator and 87% (95% CI, 77%-94%) by independent central review. No new safety signals were found in subcutaneous amivantamab. Paronychia, rash, and hypoalbuminemia were the most common treatment-emergent adverse events.
3. Impact of Amivantamab-Lazertinib on EGFR, MET Resistance Alterations in NSCLC: Danny Nguyen, MD
In an interview with Danny Nguyen, MD, medical oncologist and hematologist at City of Hope National Medical Center in Duarte, California, he discussed the importance of having a therapy in the first-line setting that could reduce the rates of EGFR and MET resistance alterations in NSCLC. Having a therapy that addresses resistance mechanisms that can be used upfront may be able to keep patients on treatment longer. The results for the combination of amivantamab plus lazertinib show that other therapy options could be possible in the future and may prevent patients from progressing within 6 months or earlier than expected.
2. CNS Metastases in EGFR-Mutant NSCLC: Emerging Therapeutic Strategies and Ongoing Challenges
Emerging therapies and evolving trial designs are highlighting the progress in central nervous system (CNS) metastases in EGFR-mutant NSCLC treatment. CNS metastases remain one of the major challenges in treating NSCLC, making it a key factor in addressing NSCLC overall. A panel held by Helena Yu, MD, research director at Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, focused on the different methods of treatment that have been tested in this population, including the use of osimertinib (Tagrisso; AstraZeneca) and amivantamab plus lazertinib. She also talked of the role of radiation therapy, stating that upfront radiation therapy could improve intracranial progression-free survival, but there has not been an overall survival benefit compared with salvage radiation therapy when the tumor progresses.
1. Updated MARIPOSA Data Highlight Clinical Impact of Upfront Dual Inhibition in EGFR+ NSCLC
Updated results of the MARIPOSA trial were presented during WCLC 2025, with results showing that amivantamab plus lazertinib was able to significantly reduce resistance and extend survival for EGFR-mutated NSCLC compared with the use of osimertinib. MET amplification occurred in 13% of the patients in the study, and EGFR secondary mutations occurred in 8% of the patients when they were treated with osimertinib. This was reduced to just 3% and 1%, respectively, in patients receiving amivantamab plus lazertinib. A total of 23% of those on osimertinib discontinued treatment within 6 months compared with only 4% of those on amivantamab.
