S. Im (Seoul, Korea, Republic of)
SNUH-Seoul National University HospitalAuthor Of 4 Presentations
Impact of ethnicity on efficacy and toxicity of cyclin d kinase 4/6 inhibitors with endocrine therapy (ID 291)
42O - Biomarker analysis from KAITLIN, a randomised phase 3 study of adjuvant trastuzumab emtansine (TDM-1; K) plus pertuzumab (P) versus trastuzumab (H) plus taxane (T) plus P after anthracyclines (AC) for high-risk HER2-positive early breast cancer (EBC) (ID 234)
Abstract
Background
KAITLIN (NCT01966471) compared adjuvant AC-KP versus AC-THP in patients with HER2-positive, high-risk EBC. A preplanned exploratory analysis assessed the relationship between invasive disease-free survival (IDFS) and biomarkers (BMs) potentially related to response.
Methods
Baseline tumor samples were used for central assessment of HER2 and pre-specified BMs including HER2 mRNA expression and PTEN IHC expression by median (med) cutoff, and activating PIK3CA hotspot mutations. The effect of treatment and BMs on IDFS was assessed via descriptive analyses.
Results
BMs were well balanced between treatment arms. No BM subgroup showed more benefit from AC-KP than AC-THP. A trend for reduced benefit with AC-KP vs AC-THP was seen in the HER2 <30% expression and 4 to <6 gene copy number subgroups (Table). No clear prognostic relationships were identified in pooled arms (PIK3CA mut vs non-mut HR=1.27 [0.92–1.74]; HER2 IHC3+ vs IHC2+ HR=0.82 [0.55–1.23]; HER2 mRNA ≥ vs < med HR=0.76 [0.56–1.03]). *HER2 IHC0/1+ (n=14), HER2 gene copy number <4 (n=20) and gene ratio <2 (n=11) excluded.
AC-THP (n=918) AC-KP (n=928) HR (95% CI) BM* n 3-yr IDFS, % n 3-yr IDFS, % 130 95.2 127 93.5 1.34 (0.65–2.80) 200 95.9 186 92.8 1.29 (0.71–2.35) 78 97.4 86 87.0 2.77 (1.08–7.09) 446 94.5 442 91.7 1.18 (0.79–1.77) 67 97.0 70 91.1 3.41 (1.10–10.60) 276 95.9 249 89.7 1.31 (0.78–2.20) 329 95.7 348 91.4 1.39 (0.87–2.22)
Conclusions
Consistent with the primary study results, AC-KP did not reduce the risk of an IDFS event compared to AC-THP in any BM subgroup. HP + chemotherapy remains the standard of care for those with high-risk HER2-positive EBC. No BMs had prognostic value in the pooled arm analyses.
Clinical trial identification
NCT01966471.
Editorial acknowledgement
Support for third-party writing assistance was provided by Tracy McNally, PhD and Holly Strausbaugh, PhD (Twist Medical, Burlingame, CA, USA), funded by F. Hoffmann-La Roche.
Legal entity responsible for the study
F. Hoffmann-La Roche.
Funding
F. Hoffmann-La Roche.
Disclosure
O. Metzger: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AbbVie; Advisory/Consultancy, Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Roche; Research grant/Funding (institution), Non-remunerated activity/ies, Co-chair Advisory Board: Pfizer. C. Lambertini: Full/Part-time employment: F. Hoffmann - La Roche Ltd. I.E. Krop: Honoraria (self), Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Daiichi Sankyo; Honoraria (self): Macrogenics; Honoraria (self): Seattle Genetics; Honoraria (self): Celltrion; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Context Therapeutics. G. Lewis Phillips: Full/Part-time employment: Genentech, Inc; Shareholder/Stockholder/Stock options: F. Hoffmann - La Roche Ltd. C.M. Perou: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Licensing/Royalties: Bioclassifier LLC; Advisory/Consultancy, Shareholder/Stockholder/Stock options, Licensing/Royalties, Officer/Board of Directors: GeneCentric Therapeutics. F. Symmans: Shareholder/Stockholder/Stock options, Licensing/Royalties, Founder shares, licensed intellectual property: Delphi Diagnostics; Shareholder/Stockholder/Stock options: IONIS Pharmaceuticals; Shareholder/Stockholder/Stock options: Eiger Pharmaceuticals. I. Melero: Honoraria (self), Research grant/Funding (institution): Roche/Genentech; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Alligator Bioscience; Honoraria (self): Bayer; Honoraria (self): Tusk Therapeutics; Honoraria (self): Gossamer Bio; Honoraria (self): Amunix; Honoraria (self): Replimune; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Medincell; Honoraria (self): Monopteros Therapeutics; Honoraria (self): Molecular Partners; Honoraria (self): Biontech; Honoraria (self): PharmaMar. N. Harbeck: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche. E.P. Winer: Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy: Carrick Therapeutics; Honoraria (self), Advisory/Consultancy: G1 Therapeutics; Honoraria (self), Research grant/Funding (institution): Genentech/Roche; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GSK; Honoraria (self), Advisory/Consultancy: Jounce; Honoraria (self), Advisory/Consultancy: Leap; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Syros; Honoraria (self), Advisory/Consultancy: Zymeworks. S-A. Im: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Hanmi; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies, Investigational agent for trial: Dae Woong. C.H. Barrios: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Mylan; Research grant/Funding (institution): Merrimack; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bayer; Research grant/Funding (institution): Astellas Pharma; Honoraria (self), Advisory/Consultancy: Eisai; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Abraxis Biosciences, BioMarin, LEO Pharma, AbbVie, Merck, and Millennium; Research grant/Funding (institution): AB Science, Asana Biosciences, Medivation, Exelixis, and Imclone Systems. H. Bonnefoi: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies: Daiichi. J.R. Gralow: Honoraria (self): Genentech/Roche; Honoraria (self): Pfizer; Honoraria (self): Puma; Honoraria (self): AstraZeneca; Honoraria (self): Immunomedics; Honoraria (self): Genomic Health; Honoraria (self): Novartis; Honoraria (self): Sandoz/Hexal; Honoraria (self): Radius; Honoraria (self): Inbiomotion. L. Gianni: Advisory/Consultancy: Hexal Sandoz; Advisory/Consultancy: Seattle Genomics; Advisory/Consultancy: Synthon; Honoraria (self), Advisory/Consultancy: Zymeworks; Advisory/Consultancy: Sanofi-Aventis; Advisory/Consultancy: Forty Seven (CD47); Advisory/Consultancy: Genenta; Advisory/Consultancy: METIS Precision Medicine; Advisory/Consultancy: Novartis; Advisory/Consultancy: Odonate Therapeutics; Honoraria (self), Advisory/Consultancy: Revolution Medicine; Advisory/Consultancy: Synaffix; Advisory/Consultancy: Menarini Ricerche; Advisory/Consultancy: Amgen; Advisory/Consultancy: Biomedical Insights Inc.; Honoraria (self): Daiichi Sankyo; Licensing/Royalties, Co-inventor of European Patent Application N. 12195182.6 and 12196177.5 titled \"PDL-1 expression in anti-HER2 therapy\": Roche. M. Toi: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Shimadzo, Yakult, Nippon Kayaku; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Kyowa-Kirin, Daiichi Sankyo; Research grant/Funding (institution): Astellas, AFI Technologies, JBCRG Association, Astehnologies, Luxonos, Shionogi, GL Science; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Speaker Bureau/Expert testimony: MSD, Exact Science, Novartis; Honoraria (self), Advisory/Consultancy: Konica Minolta, BMS; Advisory/Consultancy: Athenex Oncology, Bertis, Terumo, Kansai Medical Net. S.M. Swain: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, support for third party medical writing: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Exact Sciences (Genomic Health); Honoraria (self), Advisory/Consultancy: Molecular Templates; Honoraria (self), Advisory/Consultancy: Silverback Therapeutics; Honoraria (self), Advisory/Consultancy: Tocagen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy: Natera; Honoraria (self), Advisory/Consultancy: Athenex; Honoraria (self), Advisory/Consultancy: Bejing Medical Foundation; Research grant/Funding (institution): Kailos Genetics; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Caris Life Sciences; Advisory/Consultancy, Scientific Advisory Board: Inivata. T. Boulet: Full/Part-time employment, Employee from Parexel International GmbH contracted by Roche for Statistical services: F. Hoffmann-La Roche Ltd. C. Song: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech. S. de Haas: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche Ltd. All other authors have declared no conflicts of interest.
91O - Pooled analysis of patient (pt)-reported outcomes (PROs) in the MONALEESA (ML)-2, -3, and -7 trials: additional results and key subgroup findings (ID 240)
Abstract
Background
The phase III ML-2, -3, and -7 trials assessed ribociclib (RIB) with different endocrine therapy (ET) partners in pts with hormone receptor–positive, HER2-negative (HR+/HER2−) advanced breast cancer (ABC). Quality-of-life (QOL) results were previously reported for each ML trial and as a pooled analysis. Here, we report on individual dimensions of the EORTC QLQ-C30 PROs, including relevant pt subgroup data from a pooled analysis of the ML trials.
Methods
PROs were collected with EORTC QLQ-C30 questionnaires. QOL was assessed for all pts in ML-2, pts without prior ET for ABC in ML-3, and pts receiving RIB or placebo (PBO) + a nonsteroidal aromatase inhibitor in ML-7. A linear effects model was used to calculate the least-squares mean changes from baseline in global health status (GHS), nausea and vomiting, diarrhea, and anxiety/depression, and these were interpreted using minimally important differences. GHS was also assessed for pt subgroups including age, race, and molecular subtype by PAM50.
Results
A total of 1528 pts were included. Time to definitive deterioration (TDD) for diarrhea and anxiety/depression was prolonged for RIB vs PBO (Table). Diarrhea, anxiety/depression, and GHS across subgroups were improved or maintained from cycle 3 to end of treatment. Median TDD of GHS was longer for RIB vs PBO in pts regardless of age. Median TDD of GHS for RIB vs PBO was longer for White pts, similar for Asian pts, and shorter for pts of other races, although the n in the latter group was small. Median TDD of GHS for RIB vs PBO was longer in pts with luminal subtypes and was more than doubled for the HER2-enriched (HER2E; 30.4 vs 14.8 mo) subtype.
Conclusions
In this pooled analysis of the ML trials, RIB + ET showed delayed deterioration in QOL scores. TDD for GHS favored RIB vs PBO across most subgroups. These results support prior QOL analyses showing the value of RIB + ET in maintaining QOL for pts with HR+/HER2− ABC. aGHS by ≥10% NE, not estimable.
TDD, median mo RIB + ET (n=819) PBO + ET (n=709) HR (95% CI) All pts Nausea/vomiting ≥12 points 57.9 NE 1.04 (0.82-1.31) Diarrhea ≥10 points NE 55.2 0.76 (0.59-1.00) Anxiety/depression ≥30% 52.0 49.7 0.78 (0.63-0.96) Age (n)a <40 y (171) 35.9 23.0 0.78 (0.46-1.30) 40 - <55 y (531) 34.2 27.7 0.75 (0.57-0.99) ≥55 y (826) 42.6 35.9 0.82 (0.65-1.05) Race (n)a Asian (254) 35.9 35.8 0.94 (0.60-1.46) White (1131) 41.5 32.2 0.73 (0.59-0.89) Other (143) 33.2 46.9 1.11 (0.61-2.00) Molecular subtype (n)a Luminal A + B (628) 41.7 35.9 0.86 (0.65-1.14) HER2E (105) 30.4 14.8 0.59 (0.29-1.20) Basal-like (49) 16.5 22.4 0.84 (0.34-2.06) Normal-like (152) 47.2 50.6 0.74 (0.41-1.32)
Clinical trial identification
NCT01958021, NCT02422615, NCT02278120.
Editorial acknowledgement
This abstract was developed with editorial assistance provided by Casey Nielsen, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
P.A. Fasching: Research grant/Funding (institution): BioNTech; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Speaker Bureau/Expert testimony: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Macrogenics; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Puma; Research grant/Funding (institution): Cepheid; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: AstraZeneca. A. Bardia: Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Research grant/Funding (institution): Radius Health; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics/Gilead; Advisory/Consultancy, Research grant/Funding (institution): Biothernostics Inc.; Advisory/Consultancy, Travel/Accommodation/Expenses: Taiho; Advisory/Consultancy: Daiichi Pharma/AstraZeneca; Advisory/Consultancy: Puma; Advisory/Consultancy, Travel/Accommodation/Expenses: Phillips; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Mersana. A. Nusch: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Amgen. G. Jerusalem: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): AbbVie; Honoraria (self): Daiichi Sankyo; Advisory/Consultancy: MedImmune; Advisory/Consultancy: Merck. N.S. El Saghir: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Eli Lilly. E. Alba Conejo: Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): NanoString; Travel/Accommodation/Expenses: Celgene; Research grant/Funding (institution): Sysmex. S-A. Im: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Hanmi; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Amgen; Advisory/Consultancy: MediPacto; Research grant/Funding (institution): Roche; Honoraria (self): Lilly; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: GSK; Research grant/Funding (institution): Daewoong Pharm. W. Janni: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis. D. Chandiwana, B.R. Lanoue, A. Thuerigen, E. Gu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. N. Harbeck: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca. All other authors have declared no conflicts of interest.
93MO - Overall survival (OS) results by age subgroup from the phase III MONALEESA-7 (ML-7) trial of premenopausal patients (pts) with HR+/HER2? advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB) (ID 257)
Abstract
Background
RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), significantly prolonged OS in pre- or perimenopausal pts with HR+/HER2− ABC in ML-7 with updated results (median, 58.7 vs 48.0 mo for RIB + ET vs placebo [PBO] + ET; HR, 0.76 [95% CI, 0.61-0.96]; NCT02278120). Younger pts with HR+/HER2− ABC tend to have a poorer prognosis. We conducted an exploratory analysis to characterize outcomes in pts <40 vs ≥40 y of age.
Methods
Pre- or perimenopausal pts with HR+/HER2− ABC with no prior CDK4/6i or ET for ABC were randomized 1:1 to receive RIB or PBO plus goserelin and a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen. OS and other efficacy endpoints were evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods.
Results
The median follow-up time was 53.5 mo (data cutoff, 29 June 2020). In the RIB vs PBO arm, 98 vs 88 pts were <40 y and 237 vs 249 pts were ≥40 y. Median age (range) in RIB vs PBO was 35 y (25-39 y) vs 36 y (29-39 y) in pts <40 y, and 45 y (40-58 y) vs 46 y (40-58 y) in pts ≥40 y. In pts <40 y, RIB + ET demonstrated an OS benefit vs PBO + ET (median, 51.3 vs 40.5 mo; HR, 0.65; 95% CI, 0.43-0.98). RIB had a longer median OS vs PBO in pts ≥40 y (median, 58.8 vs 51.7 mo; HR, 0.81; 95% CI, 0.62-1.07). Similar trends were observed for OS in NSAI-treated pts and in all pts for PFS2, time to chemotherapy (CT), and CT-free survival (Table). In pts who discontinued, subsequent antineoplastic therapies were received by 77.3% vs 75.0% of pts age <40 y in RIB vs PBO arms, respectively, and 77.2% vs 79.2% of pts ≥40 y. Subsequent CDK4/6i were received in 16.0% vs 27.5% of pts age <40 y and 11.6% vs 25.7% of pts ≥40 y in RIB vs PBO arms. Adverse events were consistent with the known safety profile of ML-7. ITT, intent to treat; NR, not reached. aIn ITT.
Age <40 y Age ≥40 y RIB + ET PBO + ET RIB + ET PBO + ET OS in NSAI cohort n=78 n=66 n=170 n=181 Events, n (%) 36 (46.2) 39 (59.1) 71 (41.8) 81 (44.8) Median, mo 50.2 40.7 58.7 54.1 HR (95% CI) 0.66 (0.42-1.05) 0.85 (0.61-1.16) PFS2a n=98 n=88 n=237 n=249 Events, n (%) 54 (55.1) 60 (68.2) 123 (51.9) 161 (64.7) Median, mo 46.0 25.5 43.6 32.7 HR (95% CI) 0.59 (0.40-0.86) 0.71 (0.56-0.89) Time to first CTa n=98 n=88 n=237 n=249 Events, n (%) 40 (40.8) 43 (48.9) 104 (43.9) 130 (52.2) Median, mo NR 36.6 50.2 36.8 HR (95% CI) 0.65 (0.42-1.01) 0.69 (0.53-0.90) CT-free survivala n=98 n=88 n=237 n=249 Events, n (%) 53 (54.1) 63 (71.6) 137 (57.8) 173 (69.5) Median, mo 46.5 22.7 41.5 27.6 HR (95% CI) 0.58 (0.40-0.85) 0.68 (0.54-0.85)
Conclusions
In ML-7, RIB prolonged OS and improved post-progression outcomes in HR+/HER2− ABC, particularly in younger pts, who have a substantial unmet need.
Clinical trial identification
NCT02278120.
Editorial acknowledgement
This abstract was developed with editorial assistance provided by Chris Carter, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
Y-S. Lu: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Speaker Bureau/Expert testimony: Eisai. N.S. El Saghir: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca. S.A. Hurvitz: Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses: OBI Pharma; Research grant/Funding (institution): Bimarin; Research grant/Funding (institution): Cascadian; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): GSK; Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pieris; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Seattle Genetics. D. Tripathy: Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Polyphor; Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Leadership role: OncoPep; Advisory/Consultancy: Sellas Life Sciences Group. F. Cardoso: Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): Astellas/Medivation; Honoraria (self): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eisai; Honoraria (self): GE Oncology; Honoraria (self): Genentech; Honoraria (self): GSK; Honoraria (self): Macrogenics; Honoraria (self): Medscape; Honoraria (self): Merck-Sharp; Honoraria (self): Merus; Honoraria (self): Mylan; Honoraria (self): Mundipharma; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): Prime; Honoraria (institution): Roche. M.A. Colleoni: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy: OBI Pharma; Honoraria (self), Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Advisory/Consultancy: Celldex. S. Campos-Gomez: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb. C. Wang, Y. Wang, J.P. Zarate, A. Chakravartty: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. S-A. Im: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Hanmi; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MediPacto; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Daewoong. All other authors have declared no conflicts of interest.
Presenter Of 1 Presentation
Impact of ethnicity on efficacy and toxicity of cyclin d kinase 4/6 inhibitors with endocrine therapy (ID 291)
Moderator Of 1 Session
Author Of 1 Presentation
- S. Im (Seoul, Korea, Republic of)
- A. Tan (Charlotte, NC, United States of America)
- A. Mattar (São Paulo, Brazil)
- R. Colomer (Madrid, Spain)
- D. Stroyakovskii (Moscow, Russian Federation)
- Z. Nowecki (Warsaw, Poland)
- M. De Laurentiis (Napoli, Italy)
- J. Pierga (Paris, CE, France)
- K. Jung (Seoul, Korea, Republic of)
- C. Schem (Hamburg, Germany)
- C. Aguila (Basel, Switzerland)
- T. Badovinac Crnjevic (Basel, Switzerland)
- S. Heeson (Welwyn Garden City, United Kingdom)
- M. Shivhare (Welwyn Garden City, United Kingdom)
- A. Alexandrou (Welwyn Garden City, United Kingdom)
- E. Restuccia (Basel, Switzerland)
- C. Jackisch (Offenbach, Germany)
46P - Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) plus chemotherapy in HER2-positive early breast cancer (EBC): Safety results from the adjuvant phase of the randomised, open-label, multicentre phase 3 (neo)adjuvant FeDeriCa study
Abstract
Background
In the primary analysis of the neoadjuvant phase of the FeDeriCa study (NCT03493854; Tan AR, et al. Lancet Oncol 2021), PH FDC SC cycle 7 P + H serum trough concentrations were non-inferior to intravenous (IV) P + H, with comparable total pathological complete response rates and safety profiles. We present updated descriptive safety data that span the adjuvant phase of the study, with an additional 12 months beyond the primary analysis.
Methods
Patients (pts) with HER2-positive operable, locally advanced or inflammatory stage II–IIIC BC and left ventricular ejection fraction (LVEF) ≥55% were randomised 1:1 to eight neoadjuvant chemotherapy cycles (investigator’s choice between two standard regimens) + P IV (loading dose 840 mg, maintenance 420 mg) + H IV (8 mg/kg → 6 mg/kg) or chemotherapy + PH FDC SC (1200 mg P/600 mg H → 600 mg each as FDC SC) every 3 weeks during cycles 5–8. After surgery, pts continued adjuvant HER2-targeted treatment only, as randomised, to complete 18 cycles. Safety was assessed by NCI-CTCAE v4.
Results
Clinical cut-off was 10 July 2020. Adverse events (AEs) are shown in the table; the most common were diarrhoea, radiation skin injury and arthralgia. Infusion-/administration-related reactions within 24 hours were higher with PH FDC SC (17%) than with P + H IV (5%), all grade 1/2 and mostly due to local injection site reactions. No grade ≥3 anaphylaxis/hypersensitivity was reported in either arm. Safety population *Related cardiac failure †Clinically significant LVEF drops: 1% of pts per arm.
AEs; % of pts with ≥1: P + H IV (n = 252) PH FDC SC (n = 248) Any 87% 89% Grade ≥3 15% 11% Serious 3% 4% To monitor 46% 45% Leading to death <1%* 0 Cardiac Primary† 1% 2% Secondary 4% 1%
Conclusions
Overall safety and tolerability, including cardiac safety, of PH FDC SC in the adjuvant phase of FeDeriCa remained comparable to P + H IV, with the exception of AEs associated with the different routes of administration. Results are in line with the expectation that most AEs with PH FDC SC or P + H IV are observed during concomitant chemotherapy.
Clinical trial identification
NCT03493854 (WO40324), 2 Feb 2018.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Funding
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Disclosure
S-A. Im: Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Hanmi, GSK, Lilly, MSD, Novartis, Roche, Pfizer; Research grant/Funding (institution), Investigator-initiated clinical trial research grant through institution: AstraZeneca, Eisai, Daewoong Pharm, Roche, Pfizer; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A.R. Tan: Honoraria (self): Genentech, Novartis, Immunomedics, Celgene, AbbVie, Athenex, G1 Therapeutics, Eisai, Merck; Research grant/Funding (institution), Institutional clinical trial support: Roche/Genentech, Pfizer, Merck, Tesaro; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Mattar: Advisory/Consultancy, Advisory board consultant: Roche, Novartis, Pierre Fabre, AstraZeneca, Exact sciences; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. R. Colomer: Honoraria (self): Roche, Eli Lilly, MSD, AstraZeneca; Research grant/Funding (institution): Roche, Lilly, MSD, BMS, AstraZeneca, Pfizer, Novartis; Non-remunerated activity/ies: Roche, MSD; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. D. Stroyakovskii: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. Z. Nowecki: Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. De Laurentiis: Honoraria (self), Speaker’s honoraria and advisory board honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Advisory/Consultancy: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. J-Y. Pierga: Honoraria (self): Roche, AstraZeneca, Pfizer, Amgen, Novartis, Exact Sciences, Seagen, Lilly, Pierre Fabre, MSD; Honoraria (institution): BMS, Roche, MSD, Eisai, Novartis, Sanofi; Speaker Bureau/Expert testimony: Daiichi Sankyo; Research grant/Funding (institution): Servier, Roche, Menarini Silicon Biosystems; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. K.H. Jung: Honoraria (self), Advisory board honoraria: Roche, Novartis, AstraZeneca, Takeda, Celgene; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Schem: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Aguila: Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. T. Badovinac Crnjevic: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. S. Heeson: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. Shivhare: Shareholder/Stockholder/Stock options: Roche Products Limited; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Alexandrou: Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. E. Restuccia: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Jackisch: Honoraria (self): AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Advisory/Consultancy: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Research grant/Funding (institution): Roche, Exact Sciences; Travel/Accommodation/Expenses: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche.
Presenter Of 1 Presentation
- S. Im (Seoul, Korea, Republic of)
- A. Tan (Charlotte, NC, United States of America)
- A. Mattar (São Paulo, Brazil)
- R. Colomer (Madrid, Spain)
- D. Stroyakovskii (Moscow, Russian Federation)
- Z. Nowecki (Warsaw, Poland)
- M. De Laurentiis (Napoli, Italy)
- J. Pierga (Paris, CE, France)
- K. Jung (Seoul, Korea, Republic of)
- C. Schem (Hamburg, Germany)
- C. Aguila (Basel, Switzerland)
- T. Badovinac Crnjevic (Basel, Switzerland)
- S. Heeson (Welwyn Garden City, United Kingdom)
- M. Shivhare (Welwyn Garden City, United Kingdom)
- A. Alexandrou (Welwyn Garden City, United Kingdom)
- E. Restuccia (Basel, Switzerland)
- C. Jackisch (Offenbach, Germany)
46P - Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) plus chemotherapy in HER2-positive early breast cancer (EBC): Safety results from the adjuvant phase of the randomised, open-label, multicentre phase 3 (neo)adjuvant FeDeriCa study
Abstract
Background
In the primary analysis of the neoadjuvant phase of the FeDeriCa study (NCT03493854; Tan AR, et al. Lancet Oncol 2021), PH FDC SC cycle 7 P + H serum trough concentrations were non-inferior to intravenous (IV) P + H, with comparable total pathological complete response rates and safety profiles. We present updated descriptive safety data that span the adjuvant phase of the study, with an additional 12 months beyond the primary analysis.
Methods
Patients (pts) with HER2-positive operable, locally advanced or inflammatory stage II–IIIC BC and left ventricular ejection fraction (LVEF) ≥55% were randomised 1:1 to eight neoadjuvant chemotherapy cycles (investigator’s choice between two standard regimens) + P IV (loading dose 840 mg, maintenance 420 mg) + H IV (8 mg/kg → 6 mg/kg) or chemotherapy + PH FDC SC (1200 mg P/600 mg H → 600 mg each as FDC SC) every 3 weeks during cycles 5–8. After surgery, pts continued adjuvant HER2-targeted treatment only, as randomised, to complete 18 cycles. Safety was assessed by NCI-CTCAE v4.
Results
Clinical cut-off was 10 July 2020. Adverse events (AEs) are shown in the table; the most common were diarrhoea, radiation skin injury and arthralgia. Infusion-/administration-related reactions within 24 hours were higher with PH FDC SC (17%) than with P + H IV (5%), all grade 1/2 and mostly due to local injection site reactions. No grade ≥3 anaphylaxis/hypersensitivity was reported in either arm. Safety population *Related cardiac failure †Clinically significant LVEF drops: 1% of pts per arm.
AEs; % of pts with ≥1: P + H IV (n = 252) PH FDC SC (n = 248) Any 87% 89% Grade ≥3 15% 11% Serious 3% 4% To monitor 46% 45% Leading to death <1%* 0 Cardiac Primary† 1% 2% Secondary 4% 1%
Conclusions
Overall safety and tolerability, including cardiac safety, of PH FDC SC in the adjuvant phase of FeDeriCa remained comparable to P + H IV, with the exception of AEs associated with the different routes of administration. Results are in line with the expectation that most AEs with PH FDC SC or P + H IV are observed during concomitant chemotherapy.
Clinical trial identification
NCT03493854 (WO40324), 2 Feb 2018.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Funding
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Disclosure
S-A. Im: Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Hanmi, GSK, Lilly, MSD, Novartis, Roche, Pfizer; Research grant/Funding (institution), Investigator-initiated clinical trial research grant through institution: AstraZeneca, Eisai, Daewoong Pharm, Roche, Pfizer; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A.R. Tan: Honoraria (self): Genentech, Novartis, Immunomedics, Celgene, AbbVie, Athenex, G1 Therapeutics, Eisai, Merck; Research grant/Funding (institution), Institutional clinical trial support: Roche/Genentech, Pfizer, Merck, Tesaro; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Mattar: Advisory/Consultancy, Advisory board consultant: Roche, Novartis, Pierre Fabre, AstraZeneca, Exact sciences; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. R. Colomer: Honoraria (self): Roche, Eli Lilly, MSD, AstraZeneca; Research grant/Funding (institution): Roche, Lilly, MSD, BMS, AstraZeneca, Pfizer, Novartis; Non-remunerated activity/ies: Roche, MSD; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. D. Stroyakovskii: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. Z. Nowecki: Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. De Laurentiis: Honoraria (self), Speaker’s honoraria and advisory board honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Advisory/Consultancy: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. J-Y. Pierga: Honoraria (self): Roche, AstraZeneca, Pfizer, Amgen, Novartis, Exact Sciences, Seagen, Lilly, Pierre Fabre, MSD; Honoraria (institution): BMS, Roche, MSD, Eisai, Novartis, Sanofi; Speaker Bureau/Expert testimony: Daiichi Sankyo; Research grant/Funding (institution): Servier, Roche, Menarini Silicon Biosystems; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. K.H. Jung: Honoraria (self), Advisory board honoraria: Roche, Novartis, AstraZeneca, Takeda, Celgene; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Schem: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Aguila: Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. T. Badovinac Crnjevic: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. S. Heeson: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. Shivhare: Shareholder/Stockholder/Stock options: Roche Products Limited; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Alexandrou: Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. E. Restuccia: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Jackisch: Honoraria (self): AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Advisory/Consultancy: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Research grant/Funding (institution): Roche, Exact Sciences; Travel/Accommodation/Expenses: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche.