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Efficacy of Disitamab Vedotin in Non-small Cell Lung Cancer with Alterations: a Multicenter, Retrospective Real-world Study

Overview
Journal Front Oncol
Specialty Oncology
Date 2024 Nov 21
PMID 39568568
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Abstract

Background: Non-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 () alterations poses a substantial treatment challenge. Current -targeted therapies offer limited efficacy. Antibody-drug conjugates (ADCs) targeting have emerged as a promising therapeutic strategy. This study aimed to evaluate the clinical response to a novel ADC drug Disitamab vedotin (RC48) in advanced NSCLC with alterations.

Methods: This study conducted a retrospective review of patients harboring alterations treated with RC48 in the real world. Clinical outcomes were evaluated in terms of objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).

Results: Out of 22 patients, 21 (95.5%) received RC48 combination therapy, while one received RC48 monotherapy. The ORR of all patients reached 45.5%, and the DCR stood at 90.9%. The median PFS (mPFS) was 7.5 months. Among patients receiving RC48 combination therapy, the ORR was 47.7%, and the mPFS of 8.1 months. The combination of RC48 with platinum+/- bevacizumab resulted in the highest ORR of 71.4% (5 out of 7 patients), with TKI following at a 50.0% ORR (4 out of 8 patients). First-line (1L) treatment with RC48 showed an ORR of 62.5% (5 out of 8 patients), second-line (2L) treatments had a 57.1% ORR (4 out of 7 patients), and beyond second-line (>2L) treatments exhibited a 14.3% ORR (1 out of 7 patients). Patients with 1L, 2L, or >2L treatment had a mPFS of 8.1 months, 7.2 months, and 7.4 months, respectively. Patients with mutations or amplifications, and those with concurrent mutations and amplifications at baseline, showed mPFS of 8.1 months, 9.4 months, and 7.4 months, respectively. The mPFS was significantly longer in patients with amplification. The most common adverse events included hand-foot syndrome (54.5%), asthenia (50.0%), decreased white blood cell count (45.5%), and liver impairment (45.5%). Grade 3 adverse events occurred in one (4.5%) patient.

Conclusion: RC48, particularly in combination regimens, demonstrates promising efficacy in advanced NSCLC with alterations. These findings underscore the need for further research to validate RC48's application in clinical practice.

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