EGFR G719X + EGFR S768I

Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X-S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

The present study may be helpful in the development of new EGFR-targeted drugs based on the structure of rare mutations. Our findings may aid in developing new targeted treatments for patients with EGFR S768I and EGFR G719X + S768I mutations.

Dacomitinib is active in pts with brain metastasis, uncommon EGFR mutation, in patients with poor PS, and at 30 mg starting dose. Dacomitinib showed very good PFS with manageable safety profile.

Afatinib was an effective treatment option in patients with locally advanced and metastatic NSCLC harboring uncommon EGFR mutations. Patients with the EGFR mutations at G719X, compound G719X-S768I and tolerated dose of 20 mg or 30 mg tended to achieve a longer median TTF than those with others.

P2b, N=99, Recruiting, Teligene US | Not yet recruiting --> Recruiting | Trial completion date: Mar 2024 --> Feb 2025 | Trial primary completion date: Feb 2023 --> Aug 2024

In conclusion, the present study evidenced that Xuanwei female patients with LUAC had specific genetic profile when compared to reference Chinese female patients, indicating this high-risk female population could possibly benefit from therapy targeting KRAS mutation, uncommon EGFR mutations and HRR pathway deficiency, as well as immunotherapy.

This findings of this study might be important in establishing the correlation between routine using NGS for EGFR gene mutation diagnosis and clinical practice in the lung cancer patients.

Mefatinib has shown promising anti-tumor activity and a favorable safety profile in patients with advanced NSCLC harboring rare EGFR mutations.

This comprehensive analysis of EGFR-positive mutational landscape revealed specific genomic characteristics associated with uncommon EGFR mutations that might explain their poor response to first-generation TKIs.

P2b, N=99, Not yet recruiting, Teligene US

No intra- or intertumor heterogeneity was observed for EGFR compound mutations. Our results indicate that both EGFR mutations were truncal and selective elimination of cancer cells with uncommon EGFR mutations is unrealistic.

Afatinib is effective in pts with NSCLC with major uncommon and compound EGFR mutations, with broad activity against other uncommon EGFR mutations and some Ins20 mutations, unaffected by ethnicity. Asian pts appeared to have a high proportion of major uncommon mutations, known to be highly sensitive to afatinib.

Afatinib treatment at 40 mg daily is associated with high rates of adverse events and dose reductions; alternative strategies including pulse intermittent dosing should be evaluated prospectively. Osimertinib (with favorable safety profile and intracranial penetration) has shown promising results in this population in a phase II trial from South Korea; additional trials are ongoing.

Treatment with afatinib (40 mg/day) produced a partial response, which was maintained for 17 months with continued treatment. A literature review revealed that lung cancer with G719X/S768I compound mutation exhibited good response to EGFR-TKIs, even better than that of lung cancers with single uncommon mutations.

We report osimertinib inhibits signalling pathways and cellular growth in G719X mutant cell lines in vitro and demonstrate sustained tumor growth inhibition of PDX harboring the G719X mutation alone or in combination with L861Q and S768I. Together this data supports clinical testing of osimertinib in patients with uncommon EGFR NSCLC.

Osimertinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.

Lung cancer and genetically engineered cell lines, as well as murine xenograft models were used to evaluate the efficacy of TAS6417 and other approved/in-development EGFR TKIs (erlotinib, afatinib, osimertinib, and poziotinib). Taken together, we demonstrate that TAS6417 is a potent EGFR TKI with a broad spectrum of activity and a wider therapeutic window than most approved/in-development generations of EGFR inhibitors. Implications: TAS6417/CLN-081 is a potent EGFR TKI with a wide therapeutic window and may be effective in lung cancer patients with clinically relevant EGFR mutations.

Funding: Boehringer Ingelheim. Clinical trial identification: N/A

After postoperative recurrence, the patient was treated with osimertinib, and an excellent and long-lasting clinical response was achieved. The patient has taken osimertinib for 31.0 months and exhibited a partial response, and her follow-up is ongoing.

"The Idylla system provides a rapid, accurate and user-friendly solution to EGFR characterization, especially in time-sensitive scenarios where special expertise and staff training could be a challenge. Research Funding: None"

In this largest known clinically annotated dataset of patients with atypical EGFR-mutations treated with osi, activity was noted, though 1L clinical benefit on osi appears lower in this multicenter US cohort than in E19del or L858R. These results are comparable to the recently published prospective phase II trial (Cho et al, 2019) conducted in Korea. Patients with L861Q and Exon 19 insertion appeared to benefit the most from osi in this time on treatment retrospective analysis.