EGFR exon 20 mutation

Aspyre Clinical Test for Lung performs effectively on samples derived from fine needle aspirate rinses and pleural fluid. Using these cytology-based specimens for biomarker testing enables pathologists to perform simplified genomic profiling while preserving valuable tissue specimens, potentially reducing the need for additional invasive procedures.

Mobocertinib demonstrated clinically meaningful activity, regardless of previous exposure to amivantamab, in EGFR exon 20 insertion-positive NSCLC subjects. Acquired resistance mechanisms to mobocertinib were diverse, which poses challenges to sustained efficacy, emphasizing the need for development of a tailored subsequent therapeutic strategy.

In this editorial, we outline the preclinical and clinical evidence supporting sunvozertinib's approval, compare the efficacy and tolerability at 200mg versus 300mg, and discuss other emerging TKIs in this evolving treatment landscape. Finally, we highlight a critical paradox: despite FDA approval, sunvozertinib remains largely inaccessible to patients in the United States.

Notably, the mean duration of disease progression following EGFR-TKI initiation did not differ significantly between patients with EGFR exon 21 p.L858R mutation and those with EGFR 19-Del. Our study reveals the heterogeneity of compound EGFR mutations, and characterizes the spectrum of acquired resistance mutations to EGFR TKIs.

Findings from the phase III WU-KONG28 trial indicate that the next-generation tyrosine kinase inhibitor sunvozertinib, an approved later-line option for patients with non-small cell lung cancer harboring EGFR exon 20 insertions, also looks effective up front, besting chemotherapy. Meanwhile, updated CHRYSALIS-2 data point to amivantamab combined with lazertinib as a new option for patients with atypical EGFR mutations, with initial efficacy translating to durable overall survival.

This data confirms the efficacy and safety profile of amivantamab observed in the CHRYSALIS trial, showing a meaningful clinical benefit in a heavily pretreated real-world population.

The efficacy of sunvozertinib was superior to that of chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 20 insertions. (Funded by Dizal Pharmaceuticals; WU-KONG28 ClinicalTrials.gov number, NCT05668988.).

Results from the PAPILLON Chinese mainland population were consistent with the overall population and support the use of amivantamab plus carboplatin-pemetrexed in first-line treatment of Chinese patients with EGFR exon 20 insertion-mutated non-small cell lung cancer.

P1/2, N=345, Recruiting, Pierre Fabre Medicament | N=251 --> 345

Despite these advances, response durability remains limited for many patients, and both intrinsic and acquired resistance via on-target changes, bypass signalling and tumour evolution continues to drive unmet need. Future progress will likely depend on central nervous system-active strategies, adaptive sequencing guided by longitudinal molecular profiling and combination approaches that address pathway bypass and tumour heterogeneity.

This assay (demonstrated utilizing EGFR exon 20 mutations T790M and C797S) is extraordinarily sensitive, enabling the early substitution of a more effective therapy if the two mutations occur in a cis configuration. Moreover, these SuperSelective PCR assays can utilize DNA fragments isolated from noninvasive liquid biopsy samples, and they can be carried out on widely available spectrofluorometric thermal cyclers.

Among insured patients with advanced NSCLC receiving amivantamab in 2 L+, TTNT-D aligned with results reported in clinical trials. Before initiating amivantamab, most patients received IO, despite IO use being inconsistent with treatment guidelines and limited demonstrated benefit. HRU was similar before and during amivantamab treatment, suggesting that amivantamab does not contribute to an increase in medical services compared to treatment regimens used in earlier LOTs.