Validation of the Lung Immune Prognostic Index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the IMpower 130, 131 and 150 trials

Edouard Auclin; Matthieu Roulleaux Dugage; Teresa Gorria; Charles Vauchier; Constance Thibault; Juan Carlos Laguna; Lorena Lupinacci; Carme Crous; Marie Naigeon; Stéphane Oudard; Benjamin Besse; Laura Mezquita

doi:10.1016/j.lungcan.2024.108039

Validation of the Lung Immune Prognostic Index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the IMpower 130, 131 and 150 trials

Lung Cancer. 2024 Nov 25:199:108039. doi: 10.1016/j.lungcan.2024.108039. Online ahead of print.

Affiliations

¹ Medical Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, France; Institut Bergonié, Bordeaux, France.
² Medical Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, France; Drug Development Department, Institut Gustave Roussy, Villejuif, France.
³ Medical Oncology Department, Hospital Clinic de Barcelona, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain; Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain.
⁴ Medical Oncology Department, Hospital Italiano, Buenos Aires, Argentina.
⁵ Medical Oncology Department, Hospital Clinic de Barcelona, Barcelona, Spain.
⁶ Faculté de Pharmacie, Université Paris Saclay, Orsay, France; Immunomonitoring Laboratory, CNRS3655 and INSERM US23, Université Paris-Saclay, Villejuif, France.
⁷ Department of Medicine, Institut Gustave Roussy, Villejuif, France.
⁸ Medical Oncology Department, Hospital Clinic de Barcelona, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain; Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain. Electronic address: [email protected].

PMID: 39612560
DOI: 10.1016/j.lungcan.2024.108039

Abstract

Introduction: LIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics.

Methods: Data from patients with wild-type EGFR/ALK aNSCLC included in IMpower150, IMpower131, and IMpower130 (international phase 3 multicenter studies) treated with 1st-line CT +/- atezolizumab and/or bevacizumab were retrospectively analysed. LIPI was calculated based on the neutrophil/(leucocytes-neutrophils) (dNLR) ratio and serum LDH: good (dNLR < 3 and LDH < ULN), intermediate (dNLR ≥ 3 or LDH ≥ ULN) and poor (dNLR ≥ 3 and LDH ≥ ULN).

Results: Out of 2540 patients, 48.6 % were LIPI good, 40.8 % intermediate and 10.6 % poor. LIPI was significantly associated with treatment outcomes (PFS, OS) in the overall cohort (p < 0.001) and in each treatment cohort (all p < 0.001). After adjustment for age, smoking status, number of metastatic sites, brain or liver involvement and performance status, LIPI remained an independent prognostic factor for PFS and OS. In the LIPI good group (n = 1235), longer PFS was observed in patients treated with CT + IT + AA (median [m] PFS 11.3 vs. < 7.6 months with other regimens, p < 0.001), with a trend for OS (mOS 26.1 vs 20.7 months, p = 0.08). No regimen demonstrated significant PFS benefit in the LIPI poor group compared to chemotherapy. LIPI-good + PD-L1 ≥ 50 % (n = 105) showed long responses (mPFS of 11.1 months, mOS not reached).

Conclusions: LIPI was prognostic for PFS and OS in prospective trials in aNSCLC, regardless of the treatment regimen. LIPI poor patients derived no benefit from combination treatment. LIPI combined to PD-L1 may improve the upfront treatment selection.