Abstract 1279P
Background
CIN was shown to be associated with a small but significant survival benefit in advanced NSCLC patients treated with chemotherapy. Since neutrophils are a form of myeloid-derived suppressor cells, which negatively regulate the function of T effector cells currently perceived as the major target of immune checkpoint inhibitors, we hypothesized that even a single episode of neutropenia may trigger a long-lasting immune response and lead to extended overall survival (OS) benefits.
Methods
In this post-hoc study we have analysed a total of 1925 NSCLC patients with non-squamous histology from two phase-III trials (IMpower130, n = 723 & IMpower150, n = 1.202), which assessed the efficacy of atezolizumab in combination with different chemotherapeutic regimen. This post-hoc analysis investigated the role of the neutrophil-to-lymphocyte ratio (NLR), neutrophilia (defined as an absolute neutrophil count > 7000 G/L at baseline) and CIN (defined as an absolute neutrophil count < LLN at any time during the treatment) on the outcome of NSCLC patients treated with chemotherapy ± atezolizumab. Patients without treatment or with missing baseline values were excluded prior to the analysis (n = 36). OS and progression-free survival (PFS) were investigated using Kaplan-Meier estimates and Cox proportional hazard models. Nominal p-values were determined by log-rank tests.
Results
In the intention-to-treat population NLR ≥ 3, NLR ≥ 5 and neutrophilia were associated with a shorter PFS and OS (Table). In contrast, neutropenic patients were showing significantly improved outcomes with the most pronounced survival differences in the trial arms with CIT combinations. CIN was also able to overcome the negative prognostic value of baseline neutrophilia. Table: 1279P
| IMpower130 | IMpower150 | |||||
| Arm | A ACNP | B CNP | A ACP | B ABCP | C BCP | |
| Neutrophilia | + | OS 15.2 vs. 19.6 HR 1.34, p = 0.031 | OS 8.7 vs. 18.7 HR 1.74, p = 0.002 | OS 10.2 vs. 20.5 HR 2.09, p < 0.001 | OS 14.1 vs. 22.5 HR 1.66, p = 0.002 | OS 10.7 vs. 17.5 HR 2.12, p < 0.001 |
| - | ||||||
| CIN | + | OS 21.1 vs. 7.8 HR 0.45, p < 0.001 | OS 18.7 vs. 8.1 HR 0.44, p < 0.001 | OS 22.3 vs. 13.5 HR 0.43, p < 0.001 | OS 23.8 vs. 16.8 HR 0.61, p = 0.003 | OS 18.7 vs. 12.9 HR 0.67, p = 0.009 |
| - | ||||||
| CIN* | + | OS 18.6 vs. 6.8 HR 0.35, p < 0.001 | OS 12.0 vs. 4.8 HR 0.52, p = 0.030 | OS 21.0 vs. 9.9 HR 0.36, p = 0.016 | OS 14.3 vs. 13.5 HR 0.74, p = 0.276 | OS 12.3 vs. 10.3 HR 0.78, p = 0.392 |
| - |
OS in months A Atezolizumab, B Bevacizumab, C Carboplatin, P Paclitaxel, NP Nab-P # HR and p-values are stratified *patients with baseline neutrophilia
Conclusions
Our results underline the prognostic importance of neutropenia and the relevance of neutrophils as a therapeutic target in NSCLC patients treated with CIT.
Clinical trial identification
IMpower130: NCT02367781; IMpower150: NCT02366143.
Legal entity responsible for the study
A. Meisel.
Funding
Kantonsspital Graubünden.
Disclosure
A. Meisel: Financial Interests, Personal, Advisory Board, Travel expenses: Amgen; Financial Interests, Personal, Advisory Board, Expert testimony: Astellas; Financial Interests, Personal, Advisory Board, Travel expenses: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, Invited Speaker: Celgene; Financial Interests, Personal, Advisory Board, Travel expenses: Janssen; Financial Interests, Personal, Advisory Board, Travel expenses: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board, Invited Speaker, Travel expenses: Roche; Financial Interests, Personal, Advisory Board, Invited Speaker, Research Funding, Expert testimony: Sanofi; Financial Interests, Personal, Advisory Board, Travel expenses: Servier; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Vifor; Financial Interests, Institutional, Research Grant, Funding: Bayer; Financial Interests, Institutional, Funding, Intellectual property interests (not related to this research): Merck & Cie. M.T. Mark: Financial Interests, Personal, Advisory Board, Principal Investigator: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD. M.J. Hochmair: Financial Interests, Personal, Invited Speaker, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker, Advisory Board: Takeda. F. Cappuzzo: Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: AstraZeneca; Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: BMS; Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: MSD; Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: Eli Lilly; Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: Bayer; Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: Pfizer; Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: Roche; Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: PharmaMar; Financial Interests, Personal, Invited Speaker, Advisory role/Honoraria: Takeda. M. Reck: Financial Interests, Personal, Advisory Board, Speaker's Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Eli Lilly; Financial Interests, Personal, Advisory Board, Speaker's Bureau: MSD; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Merck Serono; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Pfizer; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Novartis; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Mirati Therapeutics; Financial Interests, Personal, Advisory Board: Samsung Bioepis; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Roche/Genentech; Financial Interests, Personal, Advisory Board, Speaker's Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Celgene; Financial Interests, Personal, Advisory Board: AbbVie. R. von Moos: Financial Interests, Personal, Invited Speaker, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: PharmaMar; Financial Interests, Advisory Board: Pfizer. F. Stenner-Liewen: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board, Travel expenses, Principal Investigator: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board, Travel expenses, Funding: Sanofi; Financial Interests, Personal, Other, Travel expenses: Roche. All other authors have declared no conflicts of interest.