588P - First real-world study with HER2 ADC in treating HER2-altered non-small cell lung cancer

Background

HER2 alterations in non-small cell lung cancer (NSCLC) are recognized as challenging therapeutic targets with unmet clinical needs. While the recent advent of HER2 ADC has shown some clinical benefits, its efficacy in real-world clinical settings remains largely uncharted. Thus, we conducted a multi-center retrospective study to assess the efficacy of HER2 ADC in a real-world context.

Methods

We continuously enrolled patients with ERBB2-altered NSCLC who underwent monotherapy or combination therapy with Disitamab Vedotin (RC48) between August 2021 and March 2023.

Results

A total of 22 patients with HER2 alterations were enrolled, including 15 with HER2 mutations, 5 with HER2 amplifications, and 2 with both. The overall objective response rate (ORR) was 45.5% (10/22), disease control rate (DCR) was 90.9% (20/22), and median progression-free survival (mPFS) stood at 7.5 months (95% CI 6.6-8.4 months). 95.5% of patients (21/22) underwent combination therapy, yielding an ORR of 47.6% (10/21). Combination regimens includes platinum, anti-angiogenesis, HER2 TKIs, and PD-1/PD-L1 inhibitors. Of note, the platinum-based combination regimen shows the highest ORR at 71.4% (5/7), following is HER2-TKI at 50% (4/8). First-line treatment patients experienced an ORR of 62.5% (5/8), whereas second-line and third-line or beyond treatments demonstrated ORRs of 57.1% (4/7) and 14.3% (1/7) respectively. No significant difference in mPFS was observed between 1L and 2L or subsequent treatments. The mPFS was notably prolonged in HER2-amplified patients and anti-HER2 naïve patients.

Conclusions

For HER2-altered NSCLC patients, RC48 combined therapies are applicable treatment options, particularly with platinum agents. RC48 combined therapies also offers a new treatment approach for patients with HER2 amplification.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.