The Use of Fam-Trastuzumab Deruxtecan-nxki in Treating ERBB2 Amplified Small Cell Lung Cancer Transformed From...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Histological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a known resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs).
• This transformation presents significant therapeutic challenges and a poor prognosis.
• EGFR mutations, RET rearrangements, and ERBB2 amplification can coexist in NSCLC.

Purpose of the Study:

• To report a case of SCLC transformation from NSCLC with concurrent ERBB2 amplification.
• To evaluate the efficacy of trastuzumab deruxtecan (T-DXd) in a patient with transformed SCLC and ERBB2 amplification.
• To highlight the potential of HER-2 directed therapies in SCLC.

Main Methods:

• A patient with metastatic NSCLC and EGFR mutation, RET rearrangement, and ERBB2 amplification was treated with osimertinib.
• The patient underwent histological transformation to SCLC while on osimertinib.
• Next-generation sequencing (NGS) confirmed continued ERBB2 amplification in the transformed SCLC.
• The patient received trastuzumab deruxtecan (T-DXd) for refractory disease.

Main Results:

• The patient achieved a partial response to T-DXd with a progression-free survival (PFS) of 13.1 months.
• Treatment with T-DXd was well-tolerated with minimal side effects.
• The observed PFS is notably better than the historically poor prognosis associated with transformed SCLC.

Conclusions:

• Trastuzumab deruxtecan (T-DXd) demonstrates potential efficacy in patients with SCLC transformed from NSCLC, particularly those with ERBB2 amplification.
• Targeting HER-2 with T-DXd may offer a viable therapeutic option for this challenging patient population.
• This case supports further investigation into HER-2 directed therapies for transformed SCLC.