Abstract 168P
Background
Emerging data suggest that liver mets are immune privileged and can induce systemic loss of tumour specific CD8+ T cells, leading to reduced anti-tumour immunity. Liver mets were shown to negatively predict the success of immunotherapy (as opposed to chemotherapy [chemo] or targeted therapy) in several cancer types. However, limited prospective data exist on the effect of immunotherapy in patients (pts) with liver mets.
Methods
This post-hoc analysis included pts with baseline liver mets from three phase 3 trials of cemiplimab (cemi; anti-PD-1) in non-small cell lung cancer (NSCLC) and cervical cancer: EMPOWER-Lung 1, EMPOWER-Lung 3 Part 2, and EMPOWER-Cervical 1. Overall survival (OS), progression free survival (PFS), and objective response rate (ORR) were analysed.
Results
Patients with baseline liver metastases represented 17% of pts in EMPOWER-Lung 1, 15% in EMPOWER-Lung 3 Part 2, and 24% in EMPOWER-Cervical 1. As expected, OS, PFS, and ORR were generally poorer in pts with liver mets regardless of treatment arms. Nonetheless, in EMPOWER-Lung 1 (1L treatment for advanced NSCLC with PD-L1 ≥50%), among pts with liver mets, cemiplimab monotherapy demonstrated notably longer OS (not reached vs 7.4 months; hazard ratio [HR] 0.38) and PFS (6.2 vs 4.2 months; HR 0.51), as well as higher ORR (29% vs 15%) vs chemo (Table). Similar improvement was observed for EMPOWER-Lung 3 Part 2 (1L cemiplimab+chemo vs placebo+chemo for advanced NSCLC with all PD-L1 levels). In EMPOWER-Cervical 1 (2L treatment of recurrent cervical cancer with all PD-L1 levels), cemiplimab showed comparable OS, PFS, and ORR vs chemo in the liver mets subgroup. Table: 168P
OS, PFS, and ORR in patients with baseline liver mets
| EMPOWER-Lung1† n=563 | EMPOWER-Lung3 Part 2 n=466 | EMPOWER-Cervical1 n=608 | |
| Liver mets n=95Cemi n=48 vschemo n=47 | Liver mets n=70Cemi+chemo n=47 vsPbo+chemo n=23 | Liver mets n=143Cemi n=78 vschemo n=65 | |
| OS median, months | NR vs 7.4 | 14.4 vs 8.9 | 5.2 vs 6.5 |
| OS HR, (95% CI) | 0.38 (0.19–0.75) | 0.61 (0.31–1.20) | 0.92 (0.62–1.36) |
| PFS median, months | 6.2 vs 4.2 | 5.4 vs 4.2 | 1.4 vs 1.9 |
| PFS HR, (95% CI) | 0.51 (0.30–0.88) | 0.64 (0.34–1.17) | 0.89 (0.62–1.28) |
| ORR, % | 29 vs 15 | 34 vs 13 | 9 vs 3 |
†PD-L1≥50% population CI, confidence interval; Pbo, placebo.
Conclusions
Despite a lower efficacy of Cemiplimab in patients with liver mets from primary lung/cervix cancer than those without, the relative benefit over prior standard-of-care regimens was preserved, and for some patients, even enhanced.
Clinical trial identification
NCT03088540 (EMPOWER-Lung 1), NCT03409614 (EMPOWER-Lung 3), NCT03257267 (EMPOWER-Cervical 1).
Editorial acknowledgement
Medical writing support was provided by Qing Zhou, PhD, ELS from Regeneron Pharmaceuticals, Inc. with editing supporting from Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc. and Sanofi.
Funding
Regeneron Pharmaceuticals, Inc. and Sanofi.
Disclosure
C. Gessner: Financial Interests, Personal, Advisory Board: GlaxoSmithKline, Pfizer, AstraZeneca, Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Berlin-Chemie, Chiesi, Boehringer Ingelheim and Sanofi. A. Sezer: Financial Interests, Institutional, Research Grant: Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Lilly, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals, Inc., and Sanofi. M. Gumus: Financial Interests, Personal, Other, Honoraria: Roche, Merck Sharp & Dohme, Gen İlaç and Novartis. K.S. Tewari: Financial Interests, Personal, Other, Honoraria: Tesaro and Clovis Oncology; Financial Interests, Personal, Advisory Role: Genentech, Tesaro, Clovis and AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Genentech, AstraZeneca, Merck, Tesaro and Clovis; Financial Interests, Personal, Research Grant: AbbVie, Genentech, Morphotek, Merck and Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, travel, accommodations, expenses: Genentech. B.J. Monk: Financial Interests, Personal, Advisory Role: Aravive, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Circulogene, Conjupro Biotherapeutics, Eisai, Geistlich, Genmab/Seattle Genetics, Gynecologic Oncology Group Foundation, ImmunoGen, Immunomedics, Incyte, Laekna Health Care, Mateon/O; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis, Janssen/Johnson & Johnson, Roche/Genentech, and Tesaro/GlaxoSmithKline. A.C. de Melo: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme Corp, Bristol Myers Squibb and Libbs Farmaceutica; Financial Interests, Personal, Other, travel support: AstraZeneca, Merck Sharp & Dohme Corp, Bristol Myers Squibb and Roche; Financial Interests, Institutional, Research Grant: Clovis Oncology, Bristol Myers Squibb, Roche, Novartis, Amgen, Merck Sharp & Dohme Corp, Lilly, Pierre Fabre, Sanofi and Pfizer. A. Oaknin: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Inmunogen, Genmab, Mersana Therapeutics, GlaxoSmithKline and Deciphera Pharmaceuticals; Financial Interests, Personal, Other, travel support: Roche, AstraZeneca and PharmaMar. S. Li: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. B. Gao: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.D. Mathias: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.E. Salvati: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. P. Rietschel: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.