Circulating tumor DNA in advanced non-small-cell lung cancer patients with HIV is associated with shorter overall survival: Results from a Phase II trial (IFCT-1001 CHIVA) - Archive ouverte HAL Access content directly
Journal Articles Lung Cancer Year : 2021

Circulating tumor DNA in advanced non-small-cell lung cancer patients with HIV is associated with shorter overall survival: Results from a Phase II trial (IFCT-1001 CHIVA)

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Xavier Quantin
Alain Makinson

Abstract

Introduction HIV is an exclusion criterion for most lung cancer (LC) trials, however LC is the most common non-AIDS-defined malignancy in people living with HIV (PLHIV), poorer prognosis than the general population. Circulating tumor DNA (ctDNA) was a prognostic marker in LC patients from the general population. This study assessed ctDNA’s prognostic value in PLHIV from a dedicated phase II trial. Methods Overall, 61 PLHIV with advanced non-squamous non-small-cell lung cancer (NSCLC) participated in the IFCT Phase II trial evaluating first-line four-cycle carboplatin (Ca) AUC5 pemetrexed (P) 500 mg/m2 induction therapy every 3 weeks, followed by P maintenance therapy. Blood samples collected before treatment were analyzed to detect ctDNA using ultra-deep targeted next-generation-sequencing (NGS). Results Appropriate samples were available from 55 PLVIH and analyzed for ctDNA detection. Including 42 males (76.4 %), 52.9 years median age, 51 smokers (92.7 %), five with non-squamous NSCLC Stage III (9%), 50 Stage IV (91 %), and performance status (PS) 0−2. ctDNA was detected in 35 patients (64 %), 22 with high and 13 with low ctDNA levels. Overall, 77 % were positive for TP53, 29 % for KRAS, and 11 % for STK11 mutations, more than one alteration was detected in 43 % of samples. Multivariate analysis showed that positive ctDNA was significantly associated with shorter PFS (HR, 4.31, 95 %CI: 2.06−8.99, p < 0.0001), and shorter OS (HR, 3.52, 95 %CI: 1.72−7.19, p < 0.001). Moreover, OS was significantly longer for patients with low ctDNA levels at diagnosis as compared to high (p = 0.01). Conclusion We show that ctDNA detection using ultra-deep NGS is an independent prognostic factor in PLHIV with advanced NSCLC.
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hal-03526372 , version 1 (14-01-2022)

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Marie Wislez, Charlotte Domblides, Laurent Greillier, Julien Mazières, Isabelle Monnet, et al.. Circulating tumor DNA in advanced non-small-cell lung cancer patients with HIV is associated with shorter overall survival: Results from a Phase II trial (IFCT-1001 CHIVA). Lung Cancer, 2021, 157, pp.124-130. ⟨10.1016/j.lungcan.2021.05.013⟩. ⟨hal-03526372⟩
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