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Found 2 Presentations For Request "lba3"
LBA3 - Randomized phase III study of selpercatinib versus cabozantinib or vandetanib in advanced, kinase inhibitor-naïve, RET-mutant medullary thyroid cancer
- Julien Hadoux (Villejuif, Cedex, France)
Abstract
Background
Selpercatinib is a highly selective and potent RET inhibitor approved for treatment of advanced
Methods
LIBRETTO-531 (NCT04211337) is a randomized phase 3 study comparing first-line selpercatinib versus physician’s choice of cabozantinib or vandetanib. Eligible patients had kinase inhibitor-naïve progressive disease documented in the 14 months prior to enrollment. The pre-planned interim efficacy analysis occurred after 59 progression-free survival (PFS) events. The primary endpoint was blinded independent central review (BICR)-assessed PFS.
Results
In total, 291 patients were randomized. Baseline characteristics were well-balanced between study arms. At a median follow-up of 12 months, median PFS by BICR was not reached with selpercatinib remaining inestimable (95% CI: NE, NE) and was 16.8 months (95% CI: 12.2, 25.1) with control (HR: 0.280, 95% CI: 0.165, 0.475; P<.0001); by investigator assessment the HR was 0.187 (95% CI: 0.109, 0.321; P<.0001). BICR overall response rate (ORR) was 69.4% (95% CI: 62.4, 75.8) with selpercatinib compared to 38.8% (95% CI: 29.1, 49.2) with control (odds ratio 3.7, 95% CI, 2.2, 6.3; P<0.0001). At a median follow-up of 15 months, overall survival (OS) was better with selpercatinib (HR: 0.374, 95% CI: 0.147, 0.949). The most common treatment-emergent adverse events observed with selpercatinib were hypertension, dry mouth, and diarrhea; and with control, diarrhea, palmar-plantar erythrodysaesthesia syndrome, and hypertension. In total, 38.9% of patients treated with selpercatinib had a dose reduction (versus 77.3% in control) and 4.7% discontinued treatment due to an adverse event (versus 26.8% in control).
Conclusions
The study met the interim analysis criteria of efficacy. First-line selpercatinib delivered markedly prolonged PFS, improved ORR, and better OS compared with MKI. This study highlights the importance of selectivity in targeting
Clinical trial identification
NCT04211337.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
J. Hadoux: Financial Interests, Personal, Advisory Board: IPSEN, Lilly, Pharma Mar; Financial Interests, Institutional, Invited Speaker: AAA, Pfizer; Financial Interests, Institutional, Advisory Board: EISAI, HRA pharma. R. Elisei: Financial Interests, Personal, Speaker, Consultant, Advisor, consulting fees: Eisai, Ipsen, Eli Lilly and Company, Loxo Oncology, Bayer, Roche; Financial Interests, Personal, Advisory Board: Eisai, Ipsen, Eli Lilly and Company, Loxo Oncology, Bayer, Roche. M.S. Brose: Financial Interests, Institutional, Funding, grant funding: Eli Lilly and Company, Bayer/Loxo Oncology, Exelixis, Blueprint Medicines; Financial Interests, Personal, Speaker, Consultant, Advisor, consulting fees: Bayer, Eli Lilly and Company; Financial Interests, Personal, Advisory Board: Eli Lilly and Company, Bayer, Exelixis, Aadi. A. Hoff: Financial Interests, Personal, Advisory Board: Knight, Bayer; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Writing Engagement: Bayer; Financial Interests, Personal, Other, Libretto-531 - Steering Committee: Eli Lilly; Financial Interests, Institutional, Local PI, A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531): Eli Lilly; Financial Interests, Institutional, Coordinating PI, A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Cabozantinib (XL184) in Subjects With Radioiodine-Refractory Differentiated Thyroid Cancer Who Have Progressed After Prior VEGFR-Targeted Therapy.: Exelixis; Financial Interests, Institutional, Local PI, Study of Efficacy and Safety of Dabrafenib Plus Trametinib in Previously Treated Patients With Locally Advanced or Metastatic, Radio-active Iodine Refractory BRAFV600E Mutation-positive Differentiated Thyroid Cancer.: Novartis; Other, Husband - President Oncologia D'OR: Oncologia D'OR. B. Robinson: Financial Interests, Personal, Leadership Role: Cochlear, Mayne Pharma; Financial Interests, Personal, Stocks or ownership: Cochlear, Mayne Pharma; Financial Interests, Personal, Advisory Board: Eisai, Loxo, Blueprint Medicines, Lilly; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Eisai. B. Jarzab: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: EwoPharma, IPSEN; Financial Interests, Personal, Advisory Board: Sobi; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Amgen, Bayer Health Care, Eisai, Exelixis, Ipsen, Sanofi-Genzyme, Novartis, Oxigene, Pfizer, Elli Lilly; Financial Interests, Research Funding: AstraZeneca, Bayer Health Care, Eisai, Exelixis, Ipsen, Sanofi-Genzyme, Novartis, Pfizer, Elli Lilly; Financial Interests, Other, clinical trials: AstraZeneca, Bayer Health Care, Eisai, Exelixis, Ipsen, Sanofi-Genzyme, Novartis, Pfizer, Elli Lilly. K. Kopeckova: Financial Interests, Personal, Expert Testimony, Treatment of thyroid cancer: Eli Lilly; Financial Interests, Personal, Advisory Board, Systemic treatment of DTC: Ipsen; Financial Interests, Personal, Invited Speaker, Breast Cancer Treatment with PARP inhibitors: AstraZeneca; Financial Interests, Personal, Other, International collaboration for thyroid cancer: EISAI. J. Wadsley: Financial Interests, Institutional, Invited Speaker, Have regularly spoken at the invitation of Lilly, and attended advisory boards: Lilly; Financial Interests, Institutional, Invited Speaker, Have regularly spoken on behalf of AAA and attended advisory boards: Novartis (AAA); Financial Interests, Institutional, Invited Speaker: Bayer, Roche, AstraZeneca, Incyte; Financial Interests, Institutional, Invited Speaker, Have been invited to speak and to advisory boards: Eisai; Financial Interests, Institutional, Advisory Board: Ipsen; Financial Interests, Personal and Institutional, Invited Speaker, Funding received to run SELIMETRY trial: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, Funding received to support SELIMETRY trial: Sanofi Genzyme; Non-Financial Interests, Principal Investigator, Local PI for LIBRETTO 531 trial: Lilly. D. Führer: Financial Interests, Personal, Advisory Board, honoraria for advisory board: Lilly, Roche, Ipsen, Eisai, Novartis; Financial Interests, Personal, Speaker’s Bureau: Lilly, Roche, Ipsen, Eisai, Novartis. B. Keam: Financial Interests, Personal, Invited Speaker: Merck, Lily, MSD Oncology, AstraZeneca, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Handok, TrialInformatics, ImmunOncia, NeoImmunetech, Beigen. E.J. Sherman: Financial Interests, Personal, Advisory Board: Eisai, Roche, Regeneron, Exelixis, Bayer; Financial Interests, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Regeneron; Financial Interests, Institutional, Invited Speaker, Also Local PI: Eli Lilly; Non-Financial Interests, Principal Investigator, PI of randomized study in thyroid cancer: Novartis. M. Tahara: Financial Interests, Personal, Advisory Board: Merck Biopharma, Ono pharma, Bristol- Myers Squibb, MSD, Pfizer, Bayer, Lilly, Rakuten Medical, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, Ono Pharma, Novartis, Pfizer, Bristol-Myers Squibb, Loxo, GSK, Lilly, Rakuten Medical, Bayer; Financial Interests, Institutional, Research Grant: Bayer. M.I. Hu: Financial Interests, Steering Committee Member: Eli Lilly & Co; Financial Interests, Institutional, Local PI: Eli Lilly & Co; Other, Co-chair of writing committee for the update of the American Thyroid Association guidelines on systemic therapies for medullary thyroid cancer (non-financial): American Thyroid Association. Y. Lin: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. P. Maeda: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. L.J. Wirth: Financial Interests, Personal, Advisory Board: Bayer, Coherus, Eli Lilly, Eisai, Exelixis; Financial Interests, Personal, Other, Consultant: Curie Therapeutics, Morphic Therapeutics, Tome Biosciences; Financial Interests, Personal, Other, DMSC: PDS Biotherapeutics; Financial Interests, Institutional, Steering Committee Member: Novartis, Eli Lilly. J. Capdevila Castillon: Financial Interests, Personal, Invited Speaker: Novartis, Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono; Financial Interests, Personal, Advisory Board: Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono; Financial Interests, Personal, Research Grant: Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications, Eisai, Bayer. All other authors have declared no conflicts of interest.
Invited Discussant LBA3
- Laura D. Locati (Milan, Italy)