2024 World Conference on Lung Cancer (WCLC) - Posters-P2.11B.04 Chemotherapy Increases Acquired Resistance to Immunotherapy in NSCLC: A Metanalysis of Aggregate and Individual Patient Data

P2.11B.04 Chemotherapy Increases Acquired Resistance to Immunotherapy in NSCLC: A Metanalysis of Aggregate and Individual Patient Data

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This study investigates the impact of platinum-based chemotherapy (PCT) on acquired resistance (AR) to immunotherapy in metastatic non-small cell lung cancer (mNSCLC). While PCT is known to reduce primary resistance, its effect on AR when combined with PD-1/PD-L1 inhibitors (ICI) or CTLA-4 inhibitors is less clear. The researchers conducted a meta-analysis of 15 randomized clinical trials, encompassing 3,538 patients, to explore this effect.<br /><br />Results showed that the addition of PCT significantly increased the rate of acquired resistance compared to regimens without PCT. Specifically, the risk of AR was higher in both combinations of chemotherapy plus ICI (ICIPCT) versus ICI alone (mono-ICI), and chemotherapy combined with CTLA-4 inhibitors (combo-ICIPCT) versus CTLA-4 inhibitors alone (combo-ICI). The relative risk of AR was calculated at 1.55 and 1.60, respectively, indicating a substantial increase in resistance when PCT is included.<br /><br />Moreover, the median duration of response (DOR) to treatment was notably shorter in patients receiving chemotherapy alongside immunotherapy compared to those receiving immunotherapy alone. For mono-ICI versus ICIPCT, the median DOR was 16.2 months and 11.8 months, respectively. A similar trend was observed for combo-ICI versus combo-ICIPCT, with medians of 18.4 and 11.6 months, respectively.<br /><br />The study concludes that adding PCT to immunotherapy in mNSCLC increases the AR rate and shortens the DOR. The data suggest a need for biomarkers to identify which patients might benefit from PCT-sparing regimens to potentially reduce AR risks. This research underscores the complex interplay between chemotherapy and immunotherapy, highlighting the importance of personalized treatment approaches based on patient-specific factors.

Asset Subtitle

Roberto FERRARA

Meta Tag

Speaker Roberto FERRARA

Topic Metastatic NSCLC – Immunotherapy

Keywords

platinum-based chemotherapy

acquired resistance

immunotherapy

metastatic non-small cell lung cancer

PD-1/PD-L1 inhibitors

CTLA-4 inhibitors

meta-analysis

duration of response

biomarkers

personalized treatment