WCLC 2025 - Posters & ePosters-P1.11.24 Real-World Evidence of Primary Resistance to First-Line Chemo-Immunotherapy in Advanced Lung Adenocarcinoma

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This multicenter retrospective-prospective study analyzed real-world data from 768 advanced lung adenocarcinoma (LUAD) patients treated with first-line chemo-immunotherapy (CT-IT) in Italy to investigate primary resistance, defined as disease progression within six months of treatment initiation. The commonly used regimen was a combination of platinum-based chemotherapy (cisplatin or carboplatin), pemetrexed, and pembrolizumab.<br /><br />Key findings showed that patients exhibiting primary resistance had significantly worse baseline characteristics: worse performance status (ECOG PS 2 in 9.9% vs. 4.5%, p=0.003), higher incidence of bone metastases (48.9% vs. 31.7%, p=0.001), liver metastases (15.6% vs. 10.3%, p=0.041), brain metastases (27.1% vs. 20.6%, p=0.048), and more than three metastatic sites (54.2% vs. 37.6%, p=0.001) compared to non-primary resistant patients. These patients had poorer treatment responses, with progressive disease as the best response in 50.4% vs. partial responses in 62.2% of others (p=0.001).<br /><br />Primary resistant patients demonstrated significantly shorter median progression-free survival (PFS) of 3.5 months versus 15.5 months and overall survival (OS) of 8.3 months versus 35.6 months (p=0.001 for both). They were also less likely to receive second-line treatments (56.0% vs. 66.5%, p=0.005), with the most common second-line regimens being docetaxel alone or combined with nintedanib. Moreover, these patients had worse responses to second-line therapy, with higher rates of disease progression (46.0% vs. 35.0%, p=0.015).<br /><br />The study highlights the urgent need for careful assessment and tailored management of LUAD patients who present with poor prognostic features predisposing to primary resistance to first-line CT-IT, as they have significantly worse survival outcomes and limited benefit from subsequent therapies. Identification of these at-risk patients may guide more personalized treatment strategies and the exploration of novel therapies.

Asset Subtitle

Marianna Peroni

Meta Tag

Speaker Marianna Peroni

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

lung adenocarcinoma

primary resistance

chemo-immunotherapy

first-line treatment

platinum-based chemotherapy

pemetrexed

pembrolizumab

progression-free survival

overall survival

second-line therapy