21O EPAC-Lung: Pooled analysis of circulating tumor cells in advanced non-small cell lung cancer
C.R. Lindsay1 , F.H. Blackhall2 , A. Carmel3 , P. Gazzaniga4 , H.J.M. Groen5 , M.G. Krebs6 , L. Muinelo-Romay7 , K. Pantel8 , E. Rossi9 , L. Terstappen10 , H. Wikman8 , J-C. Soria11 , F.F. Farace3 , A. Renehan1 , C. Dive12 , B. Besse13 , S. Michiels14 1
The Christie NHS Foundation Trust, Manchester, UK,2
Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK,3
Institut Gustave Roussy, Villejuif, France, 4
Policlinico Umberto I - Unita di Neonatologia, Patologia e Terapia Intensiva Neonatale, Rome, Italy,5
University Hospital Groningen (UMCG), Groningen, Netherlands,6
Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK,7
Health Research Institute of Santiago de Compostela (IDIS), CIBERONC, Santiago De Compostela, Spain,8
UKE Universit€atsklinikum Hamburg-Eppendorf KMTZ, Hamburg, Germany,9
Istituto Oncologico Veneto IRCCS, Padua, Italy,10
Medical Cell Biophysics, Enschede, Netherlands,11
Medimmune, Gaithersburg, MD, USA,12
Clinical & Experimental Pharmacology, Cancer Research UK Manchester Institute, Manchester, UK, 13
Department of Cancer Medicine, Gustave Roussy - Cancer Campus, Villejuif, France, 14
Team Oncostat, CESP, Gustave Roussy, Villejuif, France
Background:We assessed the clinical validity of circulating tumor cell (CTC) quantifi-cation for prognostiquantifi-cation of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a European pooled analysis of individual patient data. This is the largest study of its kind and the first to examine between-centre heterogeneity of CTC identification in NSCLC.
Methods:Nine European NSCLC CTC centers were asked to provide reported/unre-ported anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 - March 2017. We used Cox regression models, stratified by centre, to establish the association between CTC count and sur-vival. We assessed the added value of CTCs to prognostic clinico-pathological models using likelihood ratio (LR) statistics and c-indices.
Results:Seven out of nine eligible centers provided data for 550 eligible patients, including 209 patients whose prognostic information was previously unpublished. CTC counts of 2 and 5 per 75 mL were associated with reduced progression-free survival (2 CTCs: HR 1.72, p < 0001; 5 CTCs: HR 2.21, p < 0001) and overall sur-vival (2 CTCs: HR 218, p < 0001; 5 CTCs: HR 275, p < 0001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinico-pathological models (log-transformed CTCs p < 00001; 2 CTCs p < 00001; 5 CTCs p < 00001), while more moderate improvements were observed with the use of c-index models. There was minor evidence of between-center heteroge-neity in the effect on PFS, but not OS.No difference in CTC profile was observed between key NSCLC molecular subsets such as EGFR, ALK, and KRAS. Conclusions:These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC. CTC count improves prognostication when added to full clinico-pathological predictive models. 2 CTCs is an appropriate cutoff to move towards establishing clinical utility. Legal entity responsible for the study:The authors.
Funding:Has not received any funding.
Disclosure:C.R. Lindsay: Institutional funding for an ongoing phase II trial for which I am PI; Supported by Roche as part of an ESMO translational fellowship awarded in 2014-2016. F.H. Blackhall: Grants: AstraZeneca, Novartis, Pfizer, Amgen, BMS; Consultancy fees: Cell Medica, MSD; Speaker bureau: BI; Advisory board work: Regeneron, Medivation, AbbVie, Takeda, Roche, Ibsen. M.G. Krebs: Advisory board: J&J. L. Terstappen: Inventor on a number of US patents related to CellSearch, rights of which assigned to Johnson&Johnson, CellSearch kits obtained from Johnson&Johnson through a collaborative agreement with the MCBP. J-C. Soria: Consultancy fees: AZ, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, Takeda; Full time employee: MedImmune; Shareholder: AZ, Gritstone. All other authors have declared no conflicts of interest.
22P Paclitaxel/ carboplatin/ bevacizumab in non-small cell lung cancer patients induces peripheral effector CD8 T cell proliferation that could be prone for treatment with checkpoint inhibitors
D. Dumoulin1 , P. de Goeje1 , M. Poncin1 , K. Bezemer1 , H.J.M. Groen2 , E.F. Smit3 , A-M.C. Dingemans4 , A. Kunert1 , R. Hendriks1 , J.G. Aerts1 1
Pulmonology, Erasmus MC Cancer Institute, Rotterdam, Netherlands,2 University Hospital Groningen (UMCG), Groningen, Netherlands,3
Pulmonary Diseases, The Netherlands Cancer Institute, Amsterdam, Netherlands,4
Pulmonology, Maastricht University Medical Center (MUMC), Maastricht, Netherlands
Background: Checkpoint inhibitors targeting programmed death receptor (PD)-1 or PD-ligand 1 (PD-L1) became the cornerstone in the treatment of advanced NSCLC. Several phase III trials showed a better overall survival by treating with combination chemotherapy and checkpoint inhibition, suggesting that addition of chemotherapy increased the response to checkpoint inhibitors. Recently, peripheral blood biomarkers such as Ki67þPD-1þCD8 cells were found to be predictive for clinical outcome with PD-1 treatment. Knowing more about immune modulatory capacities of chemother-apy can help us to design better treatment strategies. We investigated the immune-modulatory effects of paclitaxel/carboplatin/bevacizumab (PCB), focusing on known immune populations associated with response to checkpoint inhibitors in peripheral blood.
Methods: In the NVALT 12 study, 223 patients with advanced NSCLC were enrolled to receive PCB, with or without nitroglycerin patch. At baseline and after the first and sec-ond treatment cycle, peripheral blood was drawn. By flow cytometry, the proportions of T cells and several subsets and co-inhibitory receptors of these, B cells and monocytes were determined.
Results: 6 weeks after starting treatment with PCB, the proportions of T cells were sig-nificantly increased compared to baseline values. Within the T cells subsets, prolifera-tion of CD4 T cells remained stable whereas proliferaprolifera-tion of CD8 T cells (Ki67þ) were significantly increased. The proliferating Ki67þ CD8 T cells expresses more PD-1 com-pared to non-proliferating CD8 T cells. However, patients with >2 fold increased pro-liferation of T cells did not show a better outcome.
Conclusions: Paclitaxel/ carboplatin/ bevacizumab induces proliferation of CD8 T cells which expresses more co-inhibitory checkpoint molecules. Progression free and overall survival was unchanged by this increase on its own, showing the rationale to combine PCB with checkpoint inhibition in lung cancer, as used in Impower 150.
Clinical trial identification: NCT01171170. Legal entity responsible for the study: The authors. Funding: NVALT.
Disclosure: D. Dumoulin: Speakers fee: BMS, Roche, Pfizer, Novartis. A-M.C. Dingemans: Advisory boards, lectures: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Pfizer, BMS, Amgen, Novartis, MSD, Takeda (honoraria to institution). J.G. Aerts: Advisory boards: BMS, Boehringer Ingelheim, MSD, AstraZeneca, Eli Lilly, Takeda, Amphera; Stock owner: Amphera B.V. All other authors have declared no con-flicts of interest.
23P Immunosenescence (iSenescence) correlates with progression (PD) to PD-(L)1 inhibitors (IO) and not to platinum-chemotherapy (PCT) in advanced non-small cell lung cancer (aNSCLC) patients (pts) R. Ferrara1 , M. Naigeon2 , E. Auclin3 , B. Duchemann4 , L. Cassard2 , J.J. Medhi2 , L. Boselli2 , J. Grivel2 , A. Desnoyer2 , L. Mezquita2 , L. Hendriks5 , D. Planchard2 , C. Caramella6 , J. Remon-Masip7 , S. Sangaletti8 , M.C. Garassino9 , B. Besse2 , N. Chaput2 1
Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy,2
Gustave Roussy Cancer Center, Paris, France,3
Oncology, Hopital European George Pompidou, Paris, France, 4
Hoˆpital Avicenne, Bobigny, France,5
Pulmonary Diseases, Maastricht University Medical Center (MUMC), Maastricht, Netherlands,6
Radiology, Institut Gustave Roussy, Villejuif, France,7
Vall d’Hebron University Hospital, Barcelona, Spain,8 Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy,9
Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
Background: iSenescence is a remodeling of immune functions with a multifactorial etiology (i.e. aging, chronic inflammation, cancer). Although the absence of CD28 and the expression of CD57 and KLRG1 on circulating T-lymphocytes are hallmarks of iSenescence, the characterization of such phenotype in aNSCLC pts and the correlation with clinical characteristics and benefit from IO or PCT are currently unknown. Methods: A senescent immune phenotype (SIP) defined as % of circulating CD8þCD28-CD57þKLRG1þT-lymphocytes was assessed by flow cytometry (FC) on fresh blood from aNSCLC pts treated with IO or PCT in a single institution. A log-rank
VC2019 by the European Lung Cancer Congress organisers, ESMO and IASLC. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Annals of Oncology 30 (Supplement 2): ii7–ii13, 2019 doi:10.1093/annonc/mdz073
