Abstract 298P
Background
The LIPI has been correlated with immune checkpoint inhibitors (ICI) outcomes in various tumors. We aimed to validate its prognostic value in esSCLC using data from 2 phase III trials.
Methods
Patients (pts) from the CASPIAN (NCT03043872) and IMpower133 (NCT02763579) trials were included. Both trials randomized pts to receive platinum-based chemotherapy (CT) alone or in combination with immunotherapy (IT): durvalumab ± tremelimumab (CASPIAN), or atezolizumab (IMpower133). The IT containing arms were pooled for this analysis (CT-IT). LIPI groups were defined as follows: good (dNLR
Results
A total of 1,175 pts were included: 453 received CT and 722 CT-IT. Among the pts: 64% had an ECOG 1, 38.5% were older than 65 yrs, 10.5%/39.5% had brain/liver metastases (met) at baseline. LIPI groups were distributed as follows: Good 34%, Intermediate 49%, Poor 17%. Poor LIPI was significantly associated with lower albumin and higher prevalence of liver met. LIPI stratified patients into distinct prognostic groups. Median OS was 14.6 months (m) (95% CI: 12.4–15.9) for LIPI Good, 10.9 m (10.1–11.5) for Intermediate, and 8.4 m (7.1–9.3) for Poor (p < 0.0001). Median PFS was 5.6 m (5.3–6.5) for LIPI Good, 4.9 m (4.7–5.5) for Intermediate, and 4.5 m (4.1–5.1) for Poor. In MV analysis, adjusted on gender, age, ECOG, treatment arm, brain/bone/peritoneal/liver met, LIPI remained a significant poor prognostic factor for OS (HR Poor vs. Good: 1.76, 95% CI: 1.45–2.15, p < 0.001) and PFS (HR Poor vs. Good: 1.59, 95% CI: 1.33–1.90, p < 0.001). Notably, pts with poor LIPI derived limited benefit from ICIs, although no significant interaction was observed between LIPI and treatment for OS (p=0.69) or PFS (p=0.47).
Conclusions
This post hoc analysis validates the strong prognostic utility of LIPI in esSCLC. Pts with LIPI poor have particularly poor outcomes and derive limited benefit from ICI. These findings underline the need for alternative therapeutic strategies in this subgroup.
Clinical trial identification
NCT03043872, NCT02763579.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E. Auclin: Financial Interests, Personal, Training: MSD, Janssen; Financial Interests, Personal, Advisory Board: Amgen, Sanofi; Non-Financial Interests, Personal, Other: Ipsen, Amgen; Financial Interests, Institutional, Research Grant: Ipsen. A.F. Navarro Mendivil: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Oryzon Genomics, Amgen, BMS; Financial Interests, Personal, Expert Testimony: Hengenix Biotech, MedSIR; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Takeda, Tecnofarma; Non-Financial Interests, Personal, Principal Investigator: BMS, PharmaMar, MSD, Amgen, Novartis, Debiopharm, Daiichi Sankyo, Roche, AstraZeneca. S. Cousin: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Lilly, Roche; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Daiichi Sankyo, Gilead, Takeda, Sanofi, MSD, GSK, BMS. B. Besse: Financial Interests, Institutional, Advisory Board: AbbVie, BioNTech SE, Beijing Aviston Biotechnology, Bristol Myers Squibb, CureVac AG, PharmaMar, Sanofi Aventis, Regeneron; Financial Interests, Institutional, Expert Testimony: AbbVie, Bristol Myers Squibb, Eli Lilly, Ellipse pharma Ltd, CureVac AG, F. Hoffmann-La Roche Ltd, Foghorn Therapeutics Inc., Genmab, Immunocore, Owkin, Sanofi; Financial Interests, Institutional, Invited Speaker: AbbVie, AstraZeneca, Bristol Myers Squibb, MSD, Daiichi Sankyo, Eli Lilly, Ose Immunotherapeutics, Sanofi, Servier, OSE immunotherapeutics, Sanofi, Takeda, Genmab, Taiho, AstraZeneca, Amgen, BeiGene, CureVac, Janssen, MSD, PharmaMar, Eli Lilly, Daiichi Sankyo, Enliven, Nuvalent, Ellipsis, Prelude Therapeutics; Non-Financial Interests, Personal, Leadership Role, Chair of the Scientific Chairs Council: EORTC; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Board: IFCT. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, Roche, AstraZeneca, MSD, Janssen; Financial Interests, Personal, Invited Speaker: Takeda, Roche, BMS, AstraZeneca, Janssen, Radonova, Pfizer; Financial Interests, Institutional, Invited Speaker: GILEAD; Financial Interests, Institutional, Invited Speaker, Beca SEOM Grupo Emergente 2022: AstraZeneca. All other authors have declared no conflicts of interest.