3441 - Circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) from HIV-infected patients is associated to shorter overall survival (OS): results from phase II trial (IFCT-1001 CHIVA)

Background

Lung cancer is one of the most common non-AIDS-defined malignancies. Its prognosis has been considered to be poorer in HIV-positive patients (pts) than is the general population. Circulating tumor DNA (ctDNA) has been shown to be a prognostic marker in HIV-undetermined pts. Our goal was to assess its prognosis value in HIV-positive pts.

Methods

61 HIV-positive pts with advanced non-squamous NSCLC were included in IFCT phase II trial evaluating carboplatin AUC5 pemetrexed 500 mg/m² every 3 weeks, as first-line of treatment. Baseline blood samples were collected in all pts; ctDNA was assessed by ultra-deep targeted NGS using a dedicated variant caller algorithm.

Results

55 (90%) samples were available. They were from 42 males (76.4%), 53 ± 7 years (mean ± SD), smokers (92.7%), stage III (9%) or IV (91%) and performance status (PS) 0-1 (83.6%). 18 pts were AIDS (32.7%) and 49 received HAART (89%). Mean (±SD) CD4 counts were 223/µL±222 and viral load of 39.5 [0-95499]. Disease control rate at 4 cycles was 32.7% (n = 18). PFS was 3.5 months (IC95% 2.6-4.7). OS was 8.8 months (IC95% 5.9-13.7). ctDNA was detected in 35 pts (64%) with 22 and 13 pts having high [2-49%] or low ctDNA [0.7-2%] loads, respectively. Among positive samples, 77% had a TP53 mutation and 43% had more than one alteration. Alterations in oncogene drivers were identified in KRAS, NRAS, EGFR, BRAF and MET and were mutually exclusive. ctDNA positivity was not related to clinical parameters. In multivariate analysis, AIDS status (HR 2.17 (1.09-4.32), p = 0.03) and positive ctDNA (HR 4.31 (2.06-8.99), <0.0001) were significantly associated to PFS and, PS 2 vs. 0-1 (HR 4.10 (1.62-10.36), p=.003) and positive ctDNA (HR 3.52 (1.72-7.19), p = 0.0006) to OS. Similar results were found when groups were analyzed according to ctDNA quantification, low versus high versus null.

Conclusions

ctDNA detection and quantification using ultra-deep targeted NGS is an independent prognostic factor of OS and PFS in advanced NSCLC from HIV-infected pts.

Clinical trial identification

NCT01296113.

Legal entity responsible for the study

IFCT (French Cooperative Thoracic Intergroup).

Funding

Lilly.

Editorial Acknowledgement

N/A

Disclosure

M. Wislez: Advisory boards: AstraZeneca, Roche, BMS, MSD, Novartis, Boehringer Ingelheim; Corporate-sponsored research: BMS, Boehringer Ingelheim; Travel: Roche, BMS, Novartis, Pfizer. C. Domblides: Speaker: AstraZeneca; Travel: Pierre Fabre, AstraZeneca, Pfizer, Amgen, MSD, Roche; Research funding: AstraZeneca. F. Barlesi: Consulting or advisory role: Roche/Genentech, Pfizer, Novartis, Pierre Fabre, Bristol-Myers Squibb, AstraZeneca/MedImmune, Boehringer Ingelheim, Lilly, Merck Serono, MSD Oncology, Takeda. Travel, accommodations, expenses: Roche/Genentech, Bristol-Myers Squibb, AstraZeneca/MedImmune; Honoraria: Genentech/Roche, Pfizer, Pierre Fabre, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, Novartis, Pierre Fabre, Merck Serono, MSD Oncology, Takeda. J. Mazieres: Advisory boards: AstraZeneca, Roche, BMS, MSD, Novartis, Pfizer; Research funding: AstraZeneca, Roche, BMS; Travel: Roche, BMS, Novartis, Pfizer. J. Cadranel: Principal investigator: AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, MSD, Novartis, Roche, Takeda; Consultancy: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Novartis, MSD, Pfizer, Roche; Speakers’ bureau: AstraZeneca, BMS, MSD, Pfizer. All other authors have declared no conflicts of interest.