113MO - NATALEE update: Safety and treatment (tx) duration of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2- early breast cancer (EBC)

Background

In NATALEE, RIB + NSAI showed a significant invasive disease-free survival (iDFS) benefit (HR, 0.749; 95% CI, 0.628-0.892; 1-sided P=.0006) vs NSAI alone in men and pre-/postmenopausal women with HR+/HER2− EBC. Understanding RIB tolerability is key for clinical decision making. We report RIB safety and tx duration in NATALEE.

Methods

Pts in NATALEE were randomized 1:1 to RIB (400 mg/d 3 wk on/1 wk off, 36 mo) + NSAI (letrozole or anastrozole, ≥60 mo) or NSAI alone. Men and premenopausal women also received goserelin. In this analysis, pts were followed for safety/tolerability for ≤36 mo + 30 d follow-up.

Results

At the final iDFS analysis, 1997/2525 (79.1%) pts in the safety set had discontinued RIB. Most pts (1752 [69.4%]) had completed ≥24 mo of RIB, while 1091 (43.2%) had completed 36 mo of RIB; 528 (20.9%) pts were still on RIB. The median relative dose intensity (RDI) during RIB tx was 94%.Adverse events (AEs) occurred in 2474 (98.0%) pts in the RIB arm (NSAI alone: 2145/2442 [87.8%]; Table); of these, 2368 (93.8%) were likely related to a treatment component (NSAI alone: 1566 [64.1%]). Serious AEs occurred in 357 (14.1%) pts on RIB (NSAI alone: 256 [10.5%]). AEs led to RIB dose interruptions in 1671 (66.2%) pts and RIB dose reductions in 576 (22.8%) pts. Early RIB discontinuations due to AEs were reported in 498 (19.7%) pts. Median time to AE-related discontinuation was 4 mo. Grade ≥2 neutropenia (Kaplan–Meier [KM] median, 1.0 mo) and AST/ALT elevations (KM median, not reached) generally first occurred within 3 mo. QTcF increase from baseline >60 ms occurred in 19 (0.8%) pts (NSAI alone: 2 [0.1%]). Table: 113MO

Most common AEs (>10% in RIB + NSAI arm in the safety set)

^aGrouped term per MedDRA v. 26.0^bAST, ALT, ALP, bilirubin, and GGTP elevations

Conclusions

With the majority of pts completing RIB tx, these data confirm that RIB-related AEs and dose-related adjustments occurred early, highlighting the importance of timely management of AEs. RIB was well-tolerated in NATALEE with current dose adjustment guidelines.

Clinical trial identification

CLEE011O12301C.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Molly Amador, PhD of Nucleus Global.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

C.H. Barrios: Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Novartis, Pfizer, Roche, MSD, AstraZeneca, Lilly; Financial Interests, Personal, Advisory Board, Scientific Presentations Consulting AD Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Consulting Scientific presentations: Gilead; Financial Interests, Personal, Ownership Interest, Virtual APP: THUMMI; Financial Interests, Personal, Stocks/Shares, clinical research company: Medsir; Financial Interests, Personal, Ownership Interest, Clinical Research Company: Centro de Pesquisa em Oncologia - CPO; Financial Interests, Institutional, Research Grant, research funding to the institution: Pfizer, AMGEM, GSK, Lilly, Sanofi, Merck, Biomarin, BMS, Medivation, Exelixis, Merck KGaA, Shangai Henlius Biothech, Polyphor, PharmaMar; financial interests, institutional, research grant, research funding to the institution Steering Committee: Novartis, AstraZeneca, DAIICHI; Financial Interests, Institutional, Research Grant, research funding to the institution steering committee: Roche; Financial Interests, Institutional, Invited Speaker, Research funding to the institution: Nektar, Regeneron, Janssen, OBI Pharma, Seagen, Checkpoint Therapeutics, Novocure, Aveo Oncology, Takeda, Celgene, TRIO, PPD, Syneos health, DOCS, Labcorp, IQIVIA, Parexel, Nuvisan, PSI, Medplace; Financial Interests, Institutional, Invited Speaker, Research funding to the institution Steering committee: Myovant; Non-Financial Interests, Member of Board of Directors, Member of Executive Board up to March 2023: BIG International Group; Non-Financial Interests, Leadership Role, Latin American Cooperative Oncology Group: LACOG; Non-Financial Interests, Other, Chair, International Educational Steering Group: ASCO; Non-Financial Interests, Advisory Role, Member Compliance Committee: ESMO. N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Art Tempi, Onkowissen, Medscape, Gilead, Sanofi, Zuellig pharma, Viatris; Financial Interests, Personal, Other, IDMC: Roche; Financial Interests, Personal, Advisory Board: Sandoz-Hexal, Seagen, Aptitude Health, Pfizer, Gilead, Sanofi; Financial Interests, Personal, Other, Husband: WSG (Husband); Financial Interests, Personal, Ownership Interest: West German Study Group; Financial Interests, Institutional, Funding: AstraZeneca, BMS, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Palleos, Seagen, TRIO, WSG; Non-Financial Interests, Member, Member German AGO Breast Guideline Committee: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Other, Founding Editor: Breast Care Journal. G.N. Hortobagyi: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, Member and Chair of Steering Committee: Novartis. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Ondonate, Pfizer, Puma, Prime Oncology, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre Pharmaceuticals, Samsung Bioepis, Sanofi. C. Huang: Financial Interests, Institutional, Invited Speaker, Speakers bureaus: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, speakers bureaus: AstraZeneca, Pfizer, Novartis, Roche, Eli Lilly, Gilead; Financial Interests, Institutional, Research Grant, research grants to institution: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Research grants to institution: AstraZeneca, EirGenix, Eli Lilly, MSD, OBI Pharma, Pfizer, Roche, Novartis, Seagen, Gilead, Aston Sci; Non-Financial Interests, Advisory Role, Advisory boards: Daiichi Sankyo, AstraZeneca, Eli Lilly, Pfizer, Novartis, Roche. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarini-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, PUMA; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Affiliate: SEOM. D. Juric: Financial Interests, Institutional, Research Grant: Novartis, Genentech, Syros, Eisai, Vibliome, PIC Therapeutics, Mapkure, Relay Therapeutics, Pfizer, Amgen, InventisBio, Arvinas, Takeda, Blueprint, AstraZeneca, Ribon Therapeutics, Infinity; Financial Interests, Personal, Other, Personal fees: Novartis, Genentech, Syros, Eisai, Vibliome, PIC Therapeutics, Mapkure, Relay Therapeutics. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis, AstraZeneca, AstraZeneca, Gilead, Seagen, MSD, Novartis, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. B. Xu: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker, Lectures: AstraZeneca, Pfizer, Roche, Eisai. M. De Laurentiis: Financial Interests, Personal, Invited Speaker: Pfizer, Roche, Celgene, AstraZeneca, Eisai, Eli Lilly, MSD, Pierre Fabre, Exact Science, Daiichi Sankyo, Gilead, Seagen, Menarini-Stemline, Veracyte, Takeda, Ipsen; Financial Interests, Personal, Advisory Board: Pfizer, Roche, Celgene, AstraZeneca, Eisai, Eli Lilly, MSD, Pierre Fabre, Exact Science, Daiichi Sankyo, Gilead, Seagen, Menarini-Stemline, Veracyte, Takeda, Ipsen. M. Untch: Financial Interests, Institutional, Invited Speaker, All fees and honoraria to the employer/institution: AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Seagen, Pierre Fabre, Sanofis Aventis, Myriad, Gilead, Novartis, Stemline, Genzyme, Medac; Financial Interests, Institutional, Advisory Board, All fees and honoraria to the employer/institution: AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Seagen, Pierre Fabre, Sanofis Aventis, Myriad, Gilead, Novartis, Stemline, Genzyme, Medac. K. Afenjar: Financial Interests, Personal and Institutional, Full or part-time Employment: TRIO; Other, Institutional, Other, TRIO is contracted by Novartis as CRO conducting the NATALEE trial: Novartis. E. Sum, Z. Li, N. Bolotova, W. Chiang: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: NAPO, Mylan/Viatris, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Daiichi, AstraZeneca, Gilead Sciences, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various.