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- Andres Cervantes (Valencia, Spain)
- Charles Swanton (London, United Kingdom)
LBA8 - Phase III study of cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC) of IMDC intermediate or poor risk (COSMIC-313)
- Toni K. Choueiri (Boston, United States of America)
Abstract
Background
C inhibits tyrosine kinases including MET, VEGFR, and TAM kinases (TYRO3, AXL, MER) and promotes an immune-permissive environment, which may enhance response to checkpoint inhibitors. C+N and N+I are both standards of care for first-line aRCC (N+I for intermediate or poor risk). COSMIC-313 (NCT03937219) is evaluating C in combination with N+I vs N+I in previously untreated aRCC of intermediate or poor risk and is the first study to evaluate a triplet therapy against a contemporary immuno-oncology doublet control.
Methods
This global, double-blind, randomized phase III study enrolled previously untreated patients (pts) with clear cell aRCC of IMDC intermediate or poor risk. Pts were randomized to receive C 40 mg QD or matched placebo (P), stratified by region and IMDC risk. Both treatment groups received N (3 mg/kg IV Q3W) + I (1 mg/kg IV Q3W) for 4 cycles followed by N (480 mg IV Q4W); N was administered up to 2 y. The primary endpoint was progression-free survival (PFS) by blinded independent radiology review per RECIST 1.1 in the first 550 randomized pts (PITT population). The secondary endpoint was overall survival (OS) in all randomized pts (ITT population); objective response rate (ORR) and safety were additional endpoints.
Results
From Jun 2019 to Mar 2021, 855 pts were randomized (428, C+N+I; 427, P+N+I); IMDC risk was intermediate for 75% and poor for 25%. The study met the primary PFS endpoint (HR 0.73, 95% CI, 0.57–0.94; p=0.013); median PFS was not reached (NR; 95% CI, 14.0–not estimable) for C+N+I vs 11.3 mo (95% CI, 7.7–18.2) for P+N+I. Prespecified PFS subgroup analyses will be presented. ORR (PITT population) was 43% (95% CI, 37.2–49.2) for C+N+I vs 36% (95% CI, 30.1–41.8) for P+N+I; median duration of response was NR in either treatment group. Grade 3/4 TRAEs occurred in 73% with C+N+I vs 41% with P+N+I; 3 pts (1%) in each arm had grade 5 TRAEs, and a TRAE led to discontinuation of all treatment components in 12% vs 5%.
Conclusions
C+N+I significantly improved PFS vs P+N+I in previously untreated aRCC of IMDC intermediate or poor risk. Safety was consistent with the known profiles of the treatment components. Follow-up for OS is ongoing.
Clinical trial identification
NCT03937219.
Editorial acknowledgement
Julie Lougheed, PhD; Exelixis, Inc.
Legal entity responsible for the study
Exelixis, Inc.
Funding
Exelixis, Inc.
Disclosure
T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent health; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk ($1000): UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME, mjhlifesciences.com (OncLive): MJH life sciences; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association ($1300): France Foundation; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer, WebMed; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Invited Speaker, CME, PodCast in RCC ($500.00): Caribou Publishing; Financial Interests, Personal, Invited Speaker, Reimbursement ($432.00): Kidney Cancer Association; Financial Interests, Personal, Other, member of the DSMB for clinical trial: Aravive; Financial Interests, Personal, Invited Speaker, unpaidhttps://www.accru.org/main/public/index.xhtml: ACCRU; Financial Interests, Personal, Invited Speaker, Unpaidhttps://kidneycan.org: KidneyCan; Financial Interests, Personal, Other, External Advisory Board Member: Gustave Roussy; Financial Interests, Personal, Stocks/Shares: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Nuscan ((not publicly traded)); Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National Chair: BMS, Merck, Exelixis, AstraZeneca, Takeda, Tracon, Peloton; Financial Interests, Institutional, Invited Speaker: Roche, Surface Oncology, GSK; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: Alliance Cooperative Group; Financial Interests, Institutional, Research Grant, for GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Research Grant, For Health outcomes research: Roche; Financial Interests, Institutional, Invited Speaker, leads trials as PI: Nikang; Non-Financial Interests, Leadership Role, Co-Chair of the meeting, 2019-: Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant/Track Leader: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med, Guardant, Invitae; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, pharmagenesis, and others). However, first draft frequently initiated by myself when I am 1st author: Medical Communication; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter: General US Politics; Employee at DFCI. Please see https://www.dana-farber.org/ for mission statement (non-profit hospital). I am also the past President of Medical Staff at DFCI 2015-2018: Dana-Farber Cancer Institute (DFCI); Other, Professor at HMS, Please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS); No financial interest. Institutional.Filed patents related to biomarkers of immune checkpoint blockers, and circulating free methylated DNA. No money made and some patents were abandoned: Filed patents. T.B. Powles: Financial Interests, Personal, Other, Consulting or Advisory Role: Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Esai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Merck, Merck Serono, MSD, Novartis, Pfizer, Roche, Seattle Genetics; Financial Interests, Institutional, Research Grant: Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Esai, Exelixis, Ipsen, Johnson & Johnson, Merck, Merck Serono, MSD, Novartis, Pfizer, Roche, Seattle Genetics; Financial Interests, Personal, Travel, Accommodations, Expenses: AstraZeneca, Ipsen, MSD, Pfizer, Roche. L. Albiges: Financial Interests, Institutional, Advisory Role: Astellas Pharma, AstraZeneca, Bellerophon Theraeutics, Bristol-Myers Squibb, Corvus Pharmaceuticals, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS, MSD. M. Burotto: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, MSD Oncology, Novartis; Financial Interests, Institutional, Advisory Role: Roche/Genentech; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BMS, MSD Oncology, Roche/Genentech. E. Yanez Riuz: Financial Interests, Personal, Other, Honoraria: Abbott Laboratories; Financial Interests, Personal, Advisory Role: Abbott Laboratories, Bristol-Myers Squibb, Merck Serono; Financial Interests, Institutional, Research Grant: AbbVie, Bristol-Myers Squibb, MSD, Pfizer, Roche; Financial Interests, Personal, Expert Testimony: Abbott Laboratories; Financial Interests, Personal, Travel, Accommodations, Expenses: Bristol-Myers Squibb. M. Maruzzo: Financial Interests, Personal, Advisory Role: Astellas Pharma, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, Merck Serono, MSD, Pfizer. F.A. Barros Schutz: Financial Interests, Personal, Full or part-time Employment: Ipsen; Financial Interests, Personal, Advisory Role: Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Pfizer, Roche; Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Pfizer, Roche; Financial Interests, Institutional, Research Grant: Janssen Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas Pharma, Bristol-Myers Squibb, Janssen-Cilag, Merck Sharp & Dohme, Roche. D.Y.C. Heng: Financial Interests, Personal, Advisory Role: Astellas Pharma, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Exelixis, Ipsen, Novartis, Pfizer . F. Wang: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc.; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Exelixis, Inc.. F. Mataveli: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc.. Y. Chang: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc.. C. Suarez Rodriguez: Financial Interests, Personal, Advisory Role: Astellas Pharma, Bristol-Myers Squibb, Eisai, EUSA Pharma, Ipsen, Merck Sharp & Dohme, Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Ipsen, Merck Sharp & Dohme, Pfizer, Roche/Genentech; Financial Interests, Institutional, Research Grant: AB Science, Arog, Astellas Pharma, AstraZeneca, Aveo, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Clovis Oncology, Cougar Biotechnology, Deciphera, Exelixis, GlaxoSmithKline, Incyte, Janssen Oncology, Karyopharm Therapeutics, MedImmune, Millennium, Nanobiotix, Novartis, Pfizer, Puma Biotechnology, Roche/Genentech, SFJ Pharmaceuticals Group, Teva; Financial Interests, Personal, Travel, Accommodations, Expenses: Bristol-Myers Squibb, Ipsen, Roche. R.J. Motzer: Financial Interests, Personal, Advisory Role: AstraZeneca, Calithera Biosciences, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly, Merck, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer; Financial Interests, Personal, Travel, Accommodations, Expenses: Bristol-Myers SquibbBristol-Myers Squibb. All other authors have declared no conflicts of interest.
Invited Discussant LBA8
- Sumanta K. Pal (Duarte, United States of America)
LBA9 - Duration of androgen deprivation therapy (ADT) with post-operative radiotherapy (RT) for prostate cancer: First results of the RADICALS-HD trial (ISRCTN40814031)
- Chris C. Parker (Sutton, United Kingdom)
Abstract
Background
There is good evidence on the use of ADT with primary RT as initial treatment for prostate cancer. By contrast, there is uncertainty about the role and duration of ADT with RT after radical prostatectomy (RP).
Methods
RADICALS-HD, part of the RADICALS protocol, was a randomised controlled trial to assess use and duration of ADT with post-operative RT. Key eligibility criteria were indication for RT after previous RP and no previous post-op ADT. Prior to post-op RT, pts were randomised to either no ADT (“None”), 6mo ADT (“Short”) or 24mo ADT (“Long”). 3-way randomisation was encouraged, and 2-way randomisation between None-vs-Short or Short-vs-Long also allowed. The trial was powered for the two pairwise comparisons. The primary outcome measure was metastasis-free survival (MFS). Secondary outcomes included time to salvage ADT and overall survival (OS). Toxicity assessments focused on RT with RTOG scale. The Statistical Analysis Plan is at https://doi.org/10.5281/zenodo.6586525. All confidence intervals (CI) are 95%.
Results
From 2007 to 2015, 2839 pts, including 492 in the 3-way randomisation, joined RADICALS-HD from UK, Canada & Denmark: median age 66yrs; 23% pT3b/T4; 20% Gleason 8-10, median pre-RT PSA 0.22ng/ml. Of these, 1480 pts contribute to None-vs-Short and 1523 pts to Short-vs-Long. Arms were balanced within each comparison; risk factors were more favourable in None-vs-Short than Short-vs-Long. Median follow-up was 9yrs. In None-vs-Short, based on 268 MFS events, 6mo ADT did not improve MFS (HR 0.89; CI: 0.69-1.14; 79% vs 80% event-free at 10yrs). Time to salvage ADT was delayed (HR 0.54; CI: 0.42-0.70); OS was not improved (HR 0.88; CI: 0.65-1.19). In Short-vs-Long, based on 313 MFS events, 24mo ADT improved MFS (HR 0.77; CI: 0.61-0.97; 72% vs 78% at 10yrs). Time to salvage ADT was delayed (HR 0.73; CI: 0.59-0.91); OS was not improved (HR 0.88; CI: 0.66-1.17). Pre-specified subgroup analyses will be presented.
Conclusions
In pts having post-operative RT after RP, 24mo ADT vs 6mo ADT improved both time to salvage ADT and MFS; In contrast, 6mo ADT vs no ADT improved time to salvage ADT but did not improve MFS.
Clinical trial identification
ISRCTN40814031.
Legal entity responsible for the study
MRC Clinical Trials Unit.
Funding
Cancer Research UK, Medical Research Council, NIHR CRN.
Disclosure
C.C. Parker: Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Myovant, ITM Radiopharma; Financial Interests, Institutional, Advisory Board: AAA. C. Catton: Financial Interests, Personal, Advisory Board: Bayer, AbbVie; Financial Interests, Institutional, Research Grant: Tersera Corp. H. Payne: Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Janssen, SanofiAventis, Ferring, Bayer, Novartis. All other authors have declared no conflicts of interest.
Invited Discussant LBA9
- Silke Gillessen (Bellinzona, Switzerland)
LBA10 - Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK 200 phase III study
- Melissa L. Johnson (Nashville, United States of America)
Abstract
Background
Sotorasib, an oral, irreversible KRASG12C inhibitor, is approved for the treatment of pre-treated adults with
Methods
In this global, open-label phase 3 trial, 345 patients (pts) with
Results
At a median study follow-up of 17.7 months, the study met its primary endpoint of a statistically significant improvement in PFS with sotorasib vs docetaxel (HR, 0.66 [95% CI: 0.51, 0.86], P-value, 0.002). One-year PFS was 24.8% for sotorasib vs 10.1% for docetaxel, and PFS benefit was consistent across subgroups. ORR was significantly improved for sotorasib vs docetaxel (28.1% [95% CI 21.5–35.4%] vs 13.2% [95% CI: 8.6–19.2%], respectively; P<0.001). DCR was 82.5% for sotorasib vs 60.3% for docetaxel. Overall survival was not significantly different between treatment arms, though the study was not powered for OS. Safety findings are summarized (table).
TRAEs n (%) Sotorasib (N=169) Docetaxel (N=151) Any Grade Grade ≥3 Any Grade Grade ≥3 TRAE 119 (70.4) 56 (33.1) 130 (86.1) 61 (40.4) Serious adverse event 18 (10.7) 34 (22.5) TRAE leading to discontinuation 16 (9.5) 17 (11.3) Most common TRAEs* Diarrhea 57 (33.7) 20 (11.8) 28 (18.5) 3 (2.0) Fatigue 11 (6.5) 1 (0.6) 38 (25.2) 9 (6.0) Alopecia 2 (1.2) 0 31 (20.5) 0 Nausea 24 (14.2) 2 (1.2) 30 (19.9) 1 (0.7) Anemia 5 (3.0) 1 (0.6) 27 (17.9) 5 (3.3) ALT increased 17 (10.1) 13 (7.7) 0 0 AST increased 17 (10.1) 9 (5.3) 0 0 Neutropenia 2 (1.2) 0 15 (9.9) 13 (8.6) Febrile neutropenia 0 0 8 (5.3) 8 (5.3) N represents treated patients. TRAE, treatment-related adverse event *Incidence per arm: >15%, any grade TRAE; >5%, grade ≥3 TRAEs
Conclusions
In this first, randomized phase 3 trial for a KRASG12C inhibitor, oral sotorasib demonstrated superior PFS and ORR compared to intravenous docetaxel and had a more favorable safety profile.
Clinical trial identification
NCT04303780.
Editorial acknowledgement
Medical writing assistance was provided by Liz Leight, PhD, of Amgen Inc.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, Ideaya Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, EMD Serono, G1 Therapeutics; Financial Interests, Institutional: Genentech/Roche. A.J. de Langen: Financial Interests, Institutional, Research Grant: BMS, MSD, Boehringer, AstraZeneca; Non-Financial Interests, Other: Merck Serono, Roche. D.M. Waterhouse: Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event, Travel: BMS; Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event: AstraZeneca, EMD Serono, Merck; Financial Interests, Personal, Advisory Role, Advisory Event: AbbVie, Exelixis, Eisai, Pfizer, Mirati, Regeneron/Sanofi, Fresenius Kbi; Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event, Consultant: Amgen; Financial Interests, Personal, Advisory Role, Speaker, Advisory Event: Janssen; Financial Interests, Personal, Invited Speaker, Advisory Event: Seattle Genetics; Financial Interests, Personal, Advisory Role, Advisory Event, Consultant: Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Role, Speaker (pend), Advisory Event: Eli Lilly. J. Mazieres: Financial Interests, Personal, Advisory Board: Merck, Roche, AstraZeneca, MSD, BMS, Pfizer, Hengruii Therapeutics, Daiichi, Boehringer, Pierre Fabre, Amgen; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Pierre Fabre. A.C. Dingemans: Other, Institutional, Advisory Board: Amgen, Bayer, Boehringer Ingelheim, Roche, Sanofi; Other, Institutional, Invited Speaker: AstraZeneca, Janssen, Eli Lilly, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Principal Investigator, Local PI: Amgen, Daiichi, JNJ, Eli Lilly, Mirati; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Roche; Financial Interests, Institutional, Other, Steering Committee Member: Roche. G. Mountzios: Financial Interests, Personal, Other, Consulting fees: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Payment for expert testimony: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Leadership or fiduciary role in other board, society, committee or advocacy group, unpaid: European Society for Medical Oncology working groups (Educational Publication Working Group, Adolescents and Young Adults working group); Financial Interests, Institutional, Principal Investigator: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Gilead Greece, GSK Greece, Amgen Hellas, Sanofi Greece. M. Pless: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eisei, MSD, Novartis, Pfizer, Roche, Takeda, Merck, Sanofi, Bayer, Amgen; Financial Interests, Personal, Other, Travel Grant: AstraZeneca, BMS, Boehringer Ingelheim, Roche, Takeda, Vifor; Financial Interests, Personal, Invited Speaker: Janssen, Nestle. J. Wolf: Financial Interests, Personal, Other, Personal fees: Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Eli Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. M. Schuler: Financial Interests, Personal, Other, Honoraria: Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, Novartis; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck Serono, Novartis, Roche, Sanofi, Takeda; Financial Interests, Institutional, Funding: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Other, Patents, Royalties, Other Intellectual Property - Highly sensitive method for mutation detection by PCR: Institute Patent. H. Lena: Financial Interests, Personal, Other, Personal fees: Daiichi Sankyo, AstraZeneca, Pfizer, Novartis, Amgen, MSD, Roche, BMS, Eli Lilly, Boehringer Ingelheim. F. Skoulidis: Financial Interests, Personal, Other, Consulting fees: Amgen Inc; Financial Interests, Personal, Other, lecture fees: BMS, RV Mais Promocao Eventos Ltda; Financial Interests, Personal, Other, fees for travel, food and beverage: Tango Therapeutics, AstraZeneca Pharmaceuticals, Amgen Inc; Financial Interests, Personal, Stocks/Shares, stock or stock options: BioNTech SE; Financial Interests, Personal, Stocks/Shares: Moderna Inc; Financial Interests, Institutional, Research Grant: Amgen, Mirati Therapeutics, Boehringer Ingelheim, Merck & Co, Novartis; Financial Interests, Institutional, Other, Study Chair funds: Pfizer; Financial Interests, Institutional, Research Grant, To spouse: Almmune. I. Okamoto: Financial Interests, Institutional, Research Grant: Amgen Inc, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly, Astellas Pharma, Bristol Myers Squibb, Novartis, Chugai Pharma, AbbVie; Financial Interests, Personal, Other, Personal fees: AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly, Bristol Myers Squibb, Chugai Pharma, Pfizer. S. Kim: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Takeda, Yuhan; Financial Interests, Personal, Funding, Fund for IIT: Yuhan; Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Janssen, Novartis, Takeda. H. Linardou: Financial Interests, Personal, Other, Consulting fees: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Merck, Amgen, Boehringer, Pfizer, Lilly; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, AbbVie, GSK, Amgen, Boehringer, Pfizer, Lilly; Financial Interests, Personal, Other, Payment for expert testimony: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Amgen, Boehringer, Pfizer, Lilly; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Boehringer, Pfizer; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Amgen, Boehringer, Pfizer, Lilly; Other, Personal, Leadership Role, W4O Core Committee - Unpaid: European Society for Medical Oncology; Other, Personal, Leadership Role, President of the Scientific Committee and Member of the Board of Directors - Unpaid: Hellenic Cooperative Oncology Group; Other, Personal, Leadership Role, Member of Board of Directors - Unpaid: Hellenic Foundation for Cancer Research, FairLife LCC; Other, Personal, Leadership Role, Legal Representative Member of Board of Directors - Unpaid: W4O-Hellas; Financial Interests, Personal and Institutional, Principal Investigator, PI in sponsored clinical trials, personal and institutional fees: Bristol Myers Squibb, Boehringer Ingelheim, Roche, Abbvie, Lilly, Novartis, AstraZeneca, Amgen, PPD, Parexel ILR, Qualitis, Health Data Specialist. S. Novello: Financial Interests, Personal, Speaker’s Bureau, Advisor/Speaker Bureau: AstraZeneca, AMG, BI, Sanofi, Novartis, Pfizer, Takeda, Roche, Eli Lilly, Janssen; Financial Interests, Personal, Advisory Role, Advisor/Speaker Bureau: AstraZeneca, AMG, BI, Sanofi, Novartis, Pfizer, Takeda, Roche, Eli Lilly, Janssen. Y. Chen: Other, Personal, Other, speaker faculty: Amgen, AstraZeneca, Bristol Myers Squibb, Guardant Health, Jazz Pharmaceutical, Pfizer, Takeda; Other, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Mirati; Financial Interests, Institutional, Principal Investigator: Amgen, AstraZeneca, Bristol Myers Squibb, EMD/Sorono, Helsinn, Ipsen, Merck. B. Solomon: Financial Interests, Institutional, Funding, Institutional funding for conduct of clinical trial: Amgen; Financial Interests, Personal, Advisory Board, Advisory Board/Honoraria: Amgen, Roche-Genentech, Novartis, Pfizer, AstraZeneca, Bristol Myers Squibb, Takeda, Eli Lilly, Merck Shape Dohme, Janssen. C. Obiozor, Y. Wang: Financial Interests, Personal, Full or part-time Employment, Employee and shareholder: Amgen. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, Beigene, Daiichi, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag International NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President: ASEICA (Spanish Association of Cancer Research ); Financial Interests, Other, Foundation President: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group.
LBA11 - IPSOS: Results from a phase III study of first-line (1L) atezolizumab (atezo) vs single-agent chemotherapy (chemo) in patients (pts) with NSCLC not eligible for a platinum-containing regimen
- Siow Ming Lee (London, United Kingdom)
Abstract
Background
In IMpower110 (NCT02409342), 1L atezo (anti–PD-L1) improved OS vs platinum-doublet chemo (PDC) in pts with PD-L1–high NSCLC and ECOG PS ≤1. However, ≥40% of NSCLC pts have poor ECOG PS (≥2) and/or substantial comorbidities, resulting in ineligibility for platinum-based chemo and most 1L clinical trials. IPSOS is a global, multicenter, open-label, randomised Phase 3 study of atezo vs single-agent chemo in pts ineligible for 1L PDC.
Methods
Pts had locally advanced/metastatic NSCLC without driver mutations and were ineligible for 1L PDC due to poor PS (≥2) or comorbidities in pts aged ≥70 yr. Pts were randomised 2:1 to atezo 1200 mg IV every 3 wk or single-agent chemo (vinorelbine or gemcitabine) in 3- or 4-wk cycles. The primary endpoint was OS. Key secondary endpoints were OS rates, ORR, PFS, DOR and OS and PFS in PD-L1+ pts. Safety and health-related quality of life were also assessed.
Results
453 pts were randomised (302 atezo; 151 chemo). Median age was 75 yr (range, 33-94), 31% were ≥80 yr, 72% were male and 83% had ECOG PS ≥2. At data cutoff (30 Apr 2022), with a median follow-up of 41.0 mo, atezo significantly improved OS vs chemo (stratified HR, 0.78; 95% CI: 0.63, 0.97;
Conclusions
1L atezo improved OS vs chemo in platinum-ineligible pts with NSCLC, with twice as many pts estimated to be alive at 2 yr when treated with atezo vs chemo. No new or unexpected safety concerns were seen in this poor prognosis population. aStratified.
Atezo (n=302) Chemo (n=151) mOS (95% CI), mo 10.3 (9.4, 11.9) 9.2 (5.9, 11.2) 0.78 (0.63, 0.97) 1-yr OS (95% CI), % 43.7 (37.9, 49.4) 38.6 (30.5, 46.7) – 2-yr OS (95% CI), % 24.3 (19.3, 29.4) 12.4 (6.7, 18.0) – mPFS (95% CI), mo 4.2 (3.7, 5.5) 4.0 (2.9, 5.4) 0.87 (0.70, 1.07) ORR (95% CI), % 16.9 (12.8, 21.6) 7.9 (4.2, 13.5) – mDOR (95% CI), mo 14.0 (8.1, 20.3) 7.8 (4.8, 9.7) –
Clinical trial identification
NCT03191786.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Marcia Gamboa, PhD of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
C. Schulz: Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal and Institutional, Principal Investigator: Roche; Financial Interests, Personal, Advisory Role: Roche. K. Prabhash: Financial Interests, Institutional, Advisory Board, Novartis, Merick; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Alkem. D.L. Cortinovis: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: MSD, BMS, Novartis, Boehringer Ingelheim, Amgen, Roche, Sanofi Genzyme, Takeda. A. Rittmeyer: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Boehringer-Ingelheim, Eli Lilly, GSK, Novartis, MSD, Pfizer, Roche Genentech. D. Vicente Baz: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Roche, MSD, Bayer, Pfizer, Sanofi; Financial Interests, Personal, Consultancy: AstraZeneca, Roche, MSD, Bayer, Pfizer; Financial Interests, Personal, AstraZeneca; Financial Interests, Personal, Travel, Accommodations: AstraZeneca, MSD, Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Speaker Honoraria: Takeda, Bristol Myers Squibb. R. Califano: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Lilly Oncology, Roche, Pfizer, MSD, Takeda, Amgen, Bayer, Janssen and Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly Oncology, Roche, Pfizer, MSD, Takeda, Amgen, Janssen; Financial Interests, Personal, Speaker in educational activities: Medscape and Peervoice; Financial Interests, Personal, Ownership Interest, Partnership: The Christie Private Care - LOC; Financial Interests, Institutional, Invited Speaker, Principal Investigator for clinical trial: Roche, AstraZeneca, Pfizer, Clovis, Lilly Oncology, MSD, BMS, AbbVie, Takeda, Jannsen, and Novartis; Non-Financial Interests, Member of Lung Group: EORTC. G. Liu: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Takeda, Jazz, EMD Serono, Pfizer, Merck, Novartis, Amgen; Financial Interests, Institutional, Sponsor/Funding: Takeda, Boehringer-Ingelheim; Financial Interests, Personal, Sponsor/Funding: Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, Galecto and MSD. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, Lilly, MSD, Novartis, Merck, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Mirati, Pfizer, Sanofi, Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, MSD, Roche. Y. Hu: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. S. Morris: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. E.K. Hoeglander: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. M. Connors: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. H.K.M. Vollan: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, Prime, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, Mermaid-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Mermaid-2, Poseidon, Mystic: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, Relativity 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: Beigene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Zeal-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee Pearls, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee Sapphire: Mirati; Financial Interests, Institutional, Invited Speaker, Lagoon: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; Chair Alex; Steering Committee BFAST; steering committee BEAT-Meso; Steering Committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Officer, LEadeship Role: ESMO President 2020-2022: ESMO; Non-Financial Interests, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Involved in Swiss Political Activities; Non-Financial Interests, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR; Non-Financial Interests, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Member, Association of Swiss interns and residents: ASMAC/VSAO. All other authors have declared no conflicts of interest.
Invited Discussant LBA10 and LBA11
- Natasha Leighl (Toronto, Canada)
Q&A and discussion
- All Speakers (Lugano, Switzerland)