EGFR mutation

ROS1 IHC exhibited staining in cases harboring ALK, EGFR, and KRAS mutations, including one case with concurrent EGFR and ROS1 alterations. The ROS1 SP384 clone demonstrated 71.43% sensitivity and 84.97% specificity, with a negative predictive value of 99.3%. ROS1 IHC is a valuable screening modality for molecular alterations. FISH validation is recommended, and discordant cases may require NGS or RT-PCR for rare mutations or unidentified fusion partners.

This comprehensive analysis highlights potential heterogeneous resistance to first-line osimertinib treatment, providing a rationale for combining treatments with broad activity to improve patient outcomes.

In a separate analysis of patients with matched tissue and plasma samples post-progression (n = 51), 82% had potential resistance alterations by NGS, demonstrating the complementary roles of tissue and plasma NGS. These results highlight the challenges of obtaining tissue biopsies in patients with NSCLC progressing on targeted therapy, the potential for heterogeneous resistance and the need for broad-acting treatment strategies.

The rapid progression suggests that this specific germ-line variant may confer inherent TKI resistance, potentially exacerbated by the presence of a concurrent KRAS G12V mutation and drug-drug interactions between almonertinib and antituberculosis medications. It underscores the clinical challenge of germ-line EGFR mutations and emphasizes the need for further research to establish effective therapeutic strategies for such rare genotypes.

Future research should prioritize coordinated targeting of multiple death pathways, utilize advanced computational tools integrated with multi-omics data to decipher RCD network complexity and optimize treatment prediction, and strengthen interdisciplinary translational efforts. Ultimately, a deep understanding of the RCD network paves the way for a paradigm shift toward precision therapy in lung cancer.

Osimertinib after definitive CRT demonstrated PFS benefit over placebo and a manageable safety profile in the China cohort, consistent with findings in the global LAURA population. The results support the use of osimertinib after definitive CRT as the new standard of care, globally and in China, for patients with unresectable stage III EGFR-mutated NSCLC.

P3, N=418, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jun 2026 --> Jun 2027

P1, N=8, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=30 --> 8

P2, N=78, Recruiting, L. Nicolas Gonzalez Castro, MD, PhD | Trial completion date: Nov 2026 --> Mar 2027 | Trial primary completion date: Feb 2026 --> Aug 2026

P2, N=19, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027