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Luis Paz-Ares
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ESMO-IASLC Best Abstracts (ID 62)
- Event: ELCC 2019
- Type: Proffered Paper session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/11/2019, 14:45 - 16:15, Room B
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Invited Discussant LBA1_PR and LBA3 (ID 674)
14:45 - 16:15 | Presenting Author(s): Luis Paz-Ares
- Abstract
- Presentation
Abstract not provided
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Immunotherapy in stage IV (ID 13)
- Event: ELCC 2019
- Type: Educational session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/11/2019, 09:00 - 10:30, Room B
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Combo I-O/Chemo (ID 34)
09:00 - 10:30 | Presenting Author(s): Luis Paz-Ares
- Abstract
- Presentation
Abstract not provided
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Lunch & Poster Display session (ID 58)
- Event: ELCC 2019
- Type: Poster Display session
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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180TiP - An open-label, randomized, phase I/II trial of IO102 and pembrolizumab, or IO102, pembrolizumab and chemotherapy, as first-line treatment for patients with metastatic non-small cell lung cancer (ID 208)
12:30 - 13:00 | Author(s): Luis Paz-Ares
- Abstract
Background
Immunotherapy has significantly changed the treatment landscape of non-small cell lung cancer (NSCLC) with no driver mutations. However, despite the addition of anti-PD-1/PD-L1 therapies to the clinical armamentarium only a subset of patients derives durable benefit. IO102 is a novel, second generation, HLA-A unrestricted immune modulating T-win® vaccine targeting IDO. IO102 has a dual mode of action; remodulation of the tumour micro-environment through elimination of immune suppressive cells and induction of CD8 T-cell mediated killing of IDO-expressing tumor cells. Our first-generation IDO vaccine (IO101) has shown promising antitumor activity and a favorable safety in heavily pretreated NSCLC patients (Iversen, CCR 2013).
a9ded1e5ce5d75814730bb4caaf49419 Trial design
Phase I/II, international, multicenter, open-label, randomized trial with two parallel cohorts. Cohort A: IO102 (100µg s.c.) and pembrolizumab (200 mg) (PD-L1 ≥ 50%); Cohort B: IO102, pembrolizumab and carboplatin plus pemetrexed (PD-L1 < 50%). The maximum treatment duration is 35 cycles (app. 2 years). Key eligibility criteria include metastatic NSCLC or non-squamous NSCLC (cohort B) with no prior treatment for metastatic NSCLC and no driver mutations. Phase I is a non-randomized safety run-in with 6 patients per cohort investigating one dose level of the experimental arms. Only one DLT is allowed in each cohort. Phase II is following Sargent’s two-stage, three-outcome optimum design (Sargent, ClinTrial2001) with a 2:1 randomization in the cohorts. Cohort A: IO102 and pembrolizumab versus pembrolizumab alone; Cohort B: IO102, pembrolizumab and chemotherapy vs. pembrolizumab and chemotherapy. Provision of blood and tumour tissue is required for biomarker studies. The primary endpoint is safety and objective response rate (ORR) per RECIST 1.1 in Phases I and II, respectively. Secondary endpoints include ORR per iRECIST, duration of response, progression free survival, overall survival, and biomarkers including immunoscore in tissue, tumour mutational burden and immunomonitoring in blood. The study is enrolling in Europe and US: EudraCT Number 2018-000139-28 / IND Number 018081.
d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification
EudraCT 2018-000139-28 / IND Number: 018081.
7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study
IO Biotech.
213f68309caaa4ccc14d5f99789640ad Funding
IO Biotech.
682889d0a1d3b50267a69346a750433d Disclosure
J. Spicer: Research funding, honoraria (institutional): Achilles, AstraZeneca, Bayer, BerGenBio, Boehringer Ingelheim, BMS, Celgene, Curis; Genmab, Roche, Shionogi, Starpharma, Taiho; Co-founder, shareholder: IGEM Therapeutics. P. Garrido Lopez: Consulting, advisory: I4, MSD, BMS, Boerhinger Ingelheim, Pfizer, AbbVie, Guardant Health, Novartis, Lilly, AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaker: Roche, MSD, BMS, Pfizer, Novartis, Boerhinger Ingelheim. J. Bosch-Barrera: Advisory board: MSD. E. Felip: Advisory: Blue Print Medicines, Celgene, Guardant Health, Janssen; Advisory, speaker: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda; Consultant: Boehringer Ingelheim. J. Trigo: Advisory board: Takeda, BMS, Boehringer; Speaker: BMS, Boehringer, Roche, AstraZeneca. S. Viteri: Speaker fees: BMS, Roche; Travel fees: Servier, Roche, Merck Serono; Advisory fees: Roche, AbbVie; Research fees: Roche, BMS, Servier, Merck Serono, AbbVie, Janssen. E. Schmidt: Employed: Merck & Co., Inc. A.V. Christiansen, E. Ehrnrooth: Employed: IO Biotech; Member of the Safety Monitoring Committee for the IO102-012/KN-764 trial. M-B. Zocca: Chief Executive Officer, founder: IO Biotech; Member of the Safety Monitoring Committee for the IO102-012/KN-764 trial. M.H. Andersen: Chief Scientific Officer, founder, member of BoD: IO Biotech. L. Paz-Ares: Advisory board: Roche, Lily, MSD, BMS, Boehringer Ingelheim, Novartis, AstraZeneca, Amgen, Pfizer. All other authors have declared no conflicts of interest.
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185TiP - RATIONALE 001: Tislelizumab (BGB-A317) + concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy in patients (pts) with newly diagnosed locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) (ID 252)
12:30 - 13:00 | Presenting Author(s): Luis Paz-Ares
- Abstract
Background
In pts with locally advanced, unresectable, stage III NSCLC, cCRT is associated with better survival than radiotherapy (RT) alone, but 5-y survival remains poor. Immunotherapies targeting PD-1/PD-L1 may be synergistic with cCRT, improving outcomes. Tislelizumab, an anti–PD-1 antibody, showed clinical activity/tolerability in solid tumors, including NSCLC. RATIONALE 001 is a phase III, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of first-line tislelizumab + cCRT in pts with locally advanced, unresectable, stage III NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Trial design
RATIONALE 001 aims to answer important scientific questions by employing a 3-arm study design (840 pts randomized 1:1:1) to evaluate whether the timing of giving tislelizumab earlier upfront with cCRT in addition to consolidation will improve outcomes rather than giving the anti–PD-1 as consolidation only (Table). Both tislelizumab approaches (Arms 1 and 2) will each be compared to a global standard of care, cCRT alone. Chemotherapy will be investigator’s choice (cisplatin + etoposide or carboplatin + paclitaxel). RT will be given in 2 Gy fractions (target dose of 60 Gy). Key eligibility: Locally advanced, unresectable, stage III NSCLC; stage III confirmed by FDG-PET and brain imaging; Eastern Cooperative Oncology Group performance status ≤ 1; and no prior anti–PD-1/PD-L1 therapy. PD-L1 expression assessment is not required prior to randomization. Primary endpoint: Progression-free survival. Secondary endpoints include overall survival (OS), OS at 24 mo, objective response rate, and safety. Blood and tumor biomarkers, including PD-L1 expression and tumor mutational burden, will be evaluated for correlations with clinical benefit.
d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification
NCT03745222; EudraCT: 2018-001132-22.
7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study
Celgene Corporation.
213f68309caaa4ccc14d5f99789640ad Funding
Celgene Corporation.
682889d0a1d3b50267a69346a750433d Disclosure
L. Paz-Ares: Honoraria: Lilly, MSD, BMS, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Celgene, Amgen, Incyte, Pfizer; Board member: Genomica; Institutional financial interest: AstraZeneca, BMS, MSD. S. Senan: Grants/Research support: Varian Medical Systems; Advisory/Board member: Celgene, AstraZeneca; Honoraria: Varian Medical Systems, AstraZeneca. D. Planchard: Consulting, honoraria, travel and/or institutional: AZ, BMS, BI, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Onc, Peer CME, Roche; Institutional: Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. A. Cheong: Employment, stock holder: Celgene Europe Ltd. R. Slepetis: Employment, stock holder: Celgene. M.H. Nguyen: Employment, stock holder: Celgene Corporation. E.E. Vokes: Employment: University of Chicago; Grants/Research support: AbbVie; Consultant, honoraria: AbbVie, Amgen, AstraZeneca, Biolumina, BMS, Celgene, Eli Lilly, EMD Serono, Genentech, Merck, Novartis, Regeneron. All other authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25
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Medscape Oncology - Industry Satellite Symposium (ID 36)
- Event: ELCC 2019
- Type: Industry Satellite symposium
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/12/2019, 13:00 - 14:00, Room A
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Welcome and introduction: Recent practice changing data – What do they mean in the real world? (ID 638)
13:00 - 14:00 | Presenting Author(s): Luis Paz-Ares
- Abstract
Abstract not provided
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Mini Oral session I (ID 60)
- Event: ELCC 2019
- Type: Mini Oral session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/11/2019, 08:00 - 08:50, Room A
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113O - Entrectinib in NTRK fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of patients (pts) enrolled in STARTRK-2, STARTRK-1 and ALKA-372-001 (ID 540)
08:00 - 08:50 | Author(s): Luis Paz-Ares
- Abstract
- Presentation
Background
Neurotrophic receptor tyrosine kinase (NTRK) gene fusions lead to the expression of chimeric TRK proteins with constitutively activated kinase function, conferring oncogenic potential across several tumour types. Entrectinib is a CNS-active, potent inhibitor of TRKA/B/C and ROS1. We present integrated efficacy and safety data for entrectinib in NTRK fusion-positive (NTRK-FP) solid tumours focusing on pts with NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Methods
Pts with locally advanced/metastatic NTRK-FP tumours (with or without baseline CNS disease) confirmed by nucleic acid-based methods, enrolled in global (>150 sites, 15 countries) phase 1/2 entrectinib trials (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) were included. Disease burden was assessed per BICR using RECIST v1.1, after cycle 1 (4 wks) then every 8 wks. Primary endpoints: ORR, DOR by BICR. Secondary endpoints: PFS, OS, and safety.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Outcomes in the total efficacy-evaluable population (n = 54; 10 tumour types, >19 histopathologies) are shown in the table; responses were seen in all tumour types, median PFS 11.2 mo. In the cohort of pts with NTRK-FP NSCLC (n = 10), BICR ORR was 70% (7/10). In NSCLC pts with CNS disease per investigator at baseline (n = 6), 4 had an intracranial response (2 complete, 2 partial); 1 had stable disease and 1 was not evaluable. In the safety population (68 pts with NTRK-FP solid tumors who received at least 1 dose of entrectinib), most treatment-related adverse events (TRAEs) were grade 1–2; grade 3: 32.4%, grade 4: 2.9%; no grade 5 TRAEs. TRAEs resulted in discontinuation in 4.4% and dose reduction in 39.7% of pts.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
In this integrated analysis of global multicentre clinical trials, entrectinib was well tolerated and induced clinically meaningful, durable systemic and intracranial responses in pts with NTRK-FP solid tumours, including those with NSCLC. (Table).
b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
ALKA-372-001 = EudraCT 2012-000148-88 – start date: 2015, trials ongoing STARTRK-1= NCT02097810 – start date: 2014, active, not recruiting (last update 2018) STARTRK-2 = NCT02568267 – start date: 2015, recruiting (last updated 2018).
7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
Medical writing and editorial support was provided by Charlotte Kennerley, PhD of Gardiner-Caldwell Communications, Ashfield Healthcare Communications and sponsored by Roche in accordance with Good Publication Practice guidelines.
934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
F. Hoffmann-La Roche.
213f68309caaa4ccc14d5f99789640ad Funding
Study Sponsor: Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.
682889d0a1d3b50267a69346a750433d Disclosure
L. Paz-Ares: Honoraria: Lilly, MSD, BMS, Roche, PharmaMar, Merck, AstraZeneca, Novartis, BI, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer; Research: AZ, BMS, MSD; Advisory boards: Genomica; Scientific Chair/board member: Asociación Española Contra el Cáncer. R.C. Doebele: Sponsored research: Ignyta; Advisory boards: Roche, Ignyta, Takeda, AstraZeneca, Bayer; Stock ownership: Rain Therapeutics; Patent or biological material licensing fees: Ignyta, Abbott Molecular, Rain Therapeutics. A.F. Farago: Honoraria: Foundation Medicine, Clinical Care Options Oncology, Medical Learning Institute; Research: Ignyta, Loxo, AbbVie/Stemcentrx, PharmaMar, AZ, Novartis, Merck, BMS, Amgen; Consultant: Loxo, PharmaMar, AbbVie/Stemcentrx, Genentech, AZ, Bayer, Millennium. S.V. Liu: Research: Ignyta, Genentech, Pfizer, Threshold, Clovis, Corvus, Esanex, Bayer, OncoMed, Merck, Lycera, AZ, Molecular Partners, Rain Therapeutics; Advisory boards: Ignyta, Genentech, Pfizer, Takeda, Celgene, Lilly, Taiho, BMS, AZ, Regeneron, Merck. S.P. Chawla: Honoraria/research/Advisory boards: Amgen, Roche, GSK, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, Sarc, Janssen. D. Tosi: Research funding: Novartis, Astellas, Janssen, Ipsen. C.M. Blakely: Research funding: Ignyta, Mirati, Novartis, Medimmune, Clovis. J.C. Krauss: Research funding: Boston Biomedical, AbbVie, Amgen, Isofol. D. Sigal: Advisory boards: Molecular Stethoscopye, Celularity, Curematch, Bayer; Research funding: Halozyme; Speakers bureau member: Celgene, Bayer; Stock ownership: BMS, Novartis, Halozyme. L. Bazhenova: Research funding: Beyongspring pharma; Stock ownership: EPIC Sciences; Advisory boards: Genentech, Takeda, AbbVie, Eli Lilly, Pfizer, AstraZeneca. T. John: Advisory boards: BMS, AstraZeneca, Boehringer Ingelheim, Takeda, Pfizer, Novartis, Merck, Ignyta, Roche. B. Besse: Research funding: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. J. Wolf: Advisory boards: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly MSD, Novartis, Pfizer, Roche; Corporate sponsorship for research: BMS, MSD, Novartis, Pfizer. T. Seto: Honoraria/research: Astellas, AZ, Bayer, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kissei, Kyowa HakkoKirin, Merck Serono, Mochida, MSD, Nippon, Novartis, BI, NipponKayakuOno, Pfizer, Roche, Sanofi, ShowaYakuhinKako, Taiho, Takeda, YakultHonsha, Verastem. E. Chow-Maneval: Employee: Ignyta. C. Ye, B. Simmons: Employee: Genentech. G.D. Demetri: Advisory boards: Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology; Consultant: Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, Ignyta, Roche, Loxo Oncology, Mirati Therapeutics, Epizyme, PharmaMar, Daiichi Sankyo, WIRB Copernicus Group, ZioPharm, Polaris Pharmaceuticals, M.J.Hennessey/OncLive, G1 Therapeutics, Caris Life Sciences, Champions Oncology, Bessor Pharmaceuticals, Erasca Pharmaceuticals; Consulting fees: Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, Ignyta, Roche, Loxo Oncology, Mirati Therapeutics, Epizyme, PharmaMar, Daiichi Sankyo, WIRB Copernicus Group, ZioPharm, Polaris Pharmaceuticals, M.J.Hennessey/OncLive, Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology; Research support: Bayer, Novartis, Pfizer, Janssen Oncology, Ignyta, Roche, Loxo Oncology, AbbVie, Epizyme, Adaptimmune, GlaxoSmithKline; Patent licensing fees: Novartis; Equity: Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, Caris Life Sciences, Champions Oncology, Bessor Pharmaceuticals, Erasca Pharmaceuticals.
cffcb1a185b2d7d5c44e9dc785b6bb25Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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Mini Oral session II (ID 63)
- Event: ELCC 2019
- Type: Mini Oral session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/11/2019, 16:40 - 17:40, Room C
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85O - Prevalence of programmed death ligand-1 (PD-L1) by demographic, disease and sample characteristics in unresectable, stage III NSCLC (PACIFIC) (ID 305)
16:40 - 17:40 | Author(s): Luis Paz-Ares
- Abstract
- Presentation
Background
PACIFIC (NCT02125461) was a randomised, placebo-controlled, phase 3 trial evaluating the immune checkpoint inhibitor durvalumab in patients (pts) with unresectable, Stage III non-small cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy (cCRT). Both primary endpoints of progression-free survival and overall survival were met and significantly improved with durvalumab, with similar safety, versus placebo (Antonia et al, NEJM 2017; 2018). We report exploratory analyses of the prevalence of tumour PD-L1 expression by baseline pt, disease and sample characteristics and by response to prior treatment for pts in PACIFIC.
a9ded1e5ce5d75814730bb4caaf49419 Methods
If available (provision of formalin-fixed paraffin-embedded tumour resection or biopsy samples was optional), archived pre-cCRT tumour tissue was tested retrospectively for PD-L1 tumour cell (TC) expression using the VENTANA PD-L1 (SP263) immunohistochemistry assay and scored at validated pre-specified (≥25%) and post-hoc (≥1%) cutoffs. Overall PD-L1 prevalence (regardless of treatment arm) was summarised by pt subgroups defined by various characteristics, and assessed using a Pearson’s chi-squared test for between-group differences.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Of 713 randomized pts, 451 (63.2%) were evaluable for PD-L1 status. Among PD-L1-evaluable pts, 67.2% (303/451) had TC ≥ 1% and 35.3% (159/451) had TC ≥ 25% (similar to previous reports in metastatic NSCLC). PD-L1 prevalence by various characteristics at the TC ≥ 1% cut-off are reported in the table.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
There were no important differences noted in PD-L1 prevalence between relevant subgroups at the TC ≥ 1% or TC ≥ 25% cut-offs (latter data to be presented). PD-L1 status was unaffected by sample type or age or biopsy location, suggesting expression is stable from pre-cCRT diagnostic biopsies, and supports the use of either primary tumour or lymph node biopsies for PD-L1 testing.
b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
NCT02125461.
7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.
934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
AstraZeneca.
213f68309caaa4ccc14d5f99789640ad Funding
AstraZeneca.
682889d0a1d3b50267a69346a750433d Disclosure
D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the submitted work. M.C. Garassino: Personal fees: AstraZemeca, Roche, BMS, MSD outside the conduct of this study. L. Paz-Ares: Advisory board fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merk, Boehringer Ingelheim. C. Faivre-Finn: Research funding:AstraZeneca, MSD. A. Spira: Advisory fees, institutional research support: AstraZeneca. Y. Gu, J. Whiteley, M. Scott, J. Walker: Employment, stock: AstraZeneca. C. Wadsworth, P.A. Dennis: Employment, stock: AstraZeneca, outside the conduct of the study. A-M. Boothman: Employment, stock options: AstraZeneca, outside the conduct of the study. M. Ratcliffe: Consultant fees: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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Proffered Paper session I (ID 57)
- Event: ELCC 2019
- Type: Proffered Paper session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/10/2019, 16:30 - 18:15, Room C
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LBA2 - Patient-reported outcomes (PROs) with durvalumab by PD-L1 expression in unresectable, stage III NSCLC (PACIFIC) (ID 308)
16:30 - 18:15 | Author(s): Luis Paz-Ares
- Abstract
- Presentation
Background
In the ph 3 PACIFIC study of Stage III NSCLC pts without progression after cCRT, PFS and OS were significantly improved with durva vs. pbo, with no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs.
a9ded1e5ce5d75814730bb4caaf49419 Background
In the phase 3 PACIFIC study of unresectable, Stage III NSCLC pts without progression after platinum-based concurrent chemoradiotherapy (cCRT), the primary endpoints PFS and OS were significantly improved with durvalumab versus placebo with similar safety and no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs to better understand the benefit/risk profile of durvalumab across all PD-L1 subgroups.
a9ded1e5ce5d75814730bb4caaf49419 Methods
After ≥2 cCRT cycles, pts were randomised (2:1) to durva 10 mg/kg or pbo IV q2w up to 12 mo. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25% or unknown) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from BL analysed by a mixed model for repeated measures, HRs for time to deterioration (TTD) by a stratified Cox proportional-hazards model, and ORs for improvement rates by logistic regression.
20c51b5f4e9aeb5334c90ff072e6f928 Methods
After cCRT with ≥2 chemotherapy cycles, pts were randomised (2:1) to durvalumab 10 mg/kg or placebo IV q2w up to 12 months. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25%) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from baseline (BL) analysed by a mixed model for repeated measures, hazard ratios (HRs) for time to deterioration (TTD) by a Cox proportional-hazards model, and odd ratios (ORs) for improvement rates by logistic regression.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Of 713 pts, 63% had known PD-L1 status. Compliance was high (>80% at Wk 48) across all five PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, and unknown). Most PROs remained stable; however, similar to the ITT population, clinically relevant improvements from BL to Wk 48 were observed for dysphagia and alopecia across most subgroups (4/5 and 5/5, respectively) for durva (mean changes 10.1−20.9 and 15.5−26.9) and all for pbo (10.4−19.4 and 15.8−31.3); plus improvements with pbo for TC ≥25% (12.5 for chest pain and constipation) and TC <25% (10.0 for appetite loss and arm/shoulder pain). Across most subgroups, there were no TTD differences, except those favouring durva: for TC ≥25%, chest pain (HR=0.57), physical functioning (0.60), emotional functioning (0.47), pain (0.56), and haemoptysis (0.42); and, similar to ITT, for TC ≥25%, <25%, ≥1% and <1%, ‘other pain’ (0.60, 0.57, 0.67 and 0.39, respectively). Improvement rates were also similar, except as follows, favouring durva: for TC ≥25%, role functioning (OR=2.84) and, similar to ITT, appetite loss (4.33); for TC ≥1%, diarrhoea (4.50) and haemoptysis (19.34); and, for TC<1%, ‘other pain’ (7.25); for TC<25%, the rate favoured pbo for cough (0.51).
fd69c5cf902969e6fb71d043085ddee6 Results
Of 713 pts, 63% had known PD-L1 status. Similar to the intent-to-treat (ITT) population, most PROs remained stable over time from BL across the PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, or unknown), with no clinically meaningful (CM) differences (≥10 points) for durvalumab compared to placebo. However, similar to the ITT population, CM improvements (decreases ≥10 points) from BL to Week 48 were observed for dysphagia and alopecia across most PD-L1 subgroups for both durvalumab (mean changes 8.1 [not CM]−20.9 and 15.5 − 26.9, respectively) and placebo (mean changes 10.4 − 19.4 and 15.8 − 31.3). Pre-specified and post hoc TTD analyses of PROs by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping HR and 95% CIs. Similarly, PRO improvement rates by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping OR and 95% CIs.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Similar to the ITT population, there were minimal between-Tx differences in PROs based on PD-L1 expression, supporting use of the PACIFIC regimen (durvalumab after cCRT) in all comers.
b651e8a99c4375feb982b7c2cad376e9 Conclusions
There were no CM differences in PROs between treatment arms across various PD-L1 subgroups. Results were generally consistent with those in the ITT population, suggesting that PD-L1 expression did not influence PROs in this study.
b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
NCT02125461
7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, PhD, of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.
934ce5ff971f1ab29e840a35e3ca96e9 Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and funded by AstraZeneca.
934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
AstraZeneca.
213f68309caaa4ccc14d5f99789640ad Funding
AstraZeneca.
682889d0a1d3b50267a69346a750433d Disclosure
M.C. Garassino: Personal fees: AstraZeneca, Roche, BMS, MSD. L. Paz-Ares: Advisory fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merck, Boehringer Ingelheim, outside the conduct of the study. C. Faivre-Finn: Research funding: AstraZeneca, MSD, outside the conduct of the study. A. Spira: Consultant fees, institutional research support: AstraZeneca, outside the conduct of the study. D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the conduct of the study. M. Ozguroglu: Consultant fees: Astellas; Honoraria: Janssen, outside the conduct of the study. A. Rydén, P.A. Dennis: Employment, stock: AstraZeneca. Y. Zhang, C. O’Brien: Employment, stock: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.
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