A. Chan (Nedlands, Australia)

Breast Cancer Research Centre BCRC - WA

Author Of 1 Presentation

 Conference Calendar
Proffered Paper session 1 Proffered paper

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)

Presentation Number
91O
Lecture Time
14:26 - 14:36
Speakers
Session Name
Proffered Paper session 1
Room
Channel 2
Date
Fri, 07.05.2021
Time
14:15 - 15:30

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.

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)

aGHS by ≥10% NE, not estimable.

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.

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Author Of 1 Presentation

 On-Demand ePoster Display

45P - Long-term Efficacy of Neratinib in HER2-Positive Early-Stage Breast Cancer: Overall Survival and Central Nervous System Outcomes from the Phase 3 ExteNET Trial

Abstract

Background

Neratinib (Nerlynx®) is an irreversible pan-HER inhibitor that significantly improves invasive disease-free survival (iDFS) vs placebo as extended adjuvant therapy in HER2-positive (HER2+) early-stage breast cancer (eBC) after trastuzumab-based therapy. The phase III ExteNET trial (NCT00878709) showed an absolute iDFS benefit of 2.5% and distant disease-free survival benefit of 1.7% with neratinib after 5 years’ follow-up. The brain is a common first site of metastasis after HER2-directed adjuvant therapy for eBC. To date, no HER2-directed therapies have prevented central nervous system (CNS) metastases in this setting.

Methods

Women with HER2+ eBC who had completed adjuvant therapy (± neoadjuvant therapy) with trastuzumab + chemotherapy were randomized to oral neratinib 240 mg/d or placebo for 1y. OS was analyzed after 248 events (powered for the ITT population). CNS outcomes: cumulative incidence of CNS recurrences (time from randomization to CNS recurrence as first distant recurrence); CNS disease-free survival (CNS-DFS, time from randomization to any CNS recurrence or death from any cause). Cut-off dates: 5y (Mar 2017); OS (Jul 2019).

Results

2840 patients were randomized (1420 per group). After a median follow-up of 8.1y, 8y OS rates were 90.1% (95% CI 88.3‒91.6) for neratinib and 90.2% (95% CI 88.4‒91.7) for placebo (absolute difference –0.1%; stratified HR=0.95; 95% CI 0.75‒1.21; p=0.6914). At 5y, cumulative incidence of CNS recurrences was 1.3% (95% CI 0.8–2.1) with neratinib and 1.8% (95% CI 1.2–2.7) with placebo, and CNS-DFS rates were 97.5% (95% CI 96.4–98.3) and 96.4% (95% CI 95.2–97.4), respectively (HR=0.73; 95% CI 0.45–1.17). No new safety signals were reported.

Conclusions

There were fewer deaths with neratinib than placebo in ExteNET, but the results did not reach statistical significance. Long-term CNS outcomes at 5y were also improved with neratinib. Neratinib is the first HER2-directed agent to show a trend towards improved CNS outcomes in HER2+ eBC, providing further support for current NCCN guidelines that recommend neratinib-based therapy for brain metastases from HER2-positive breast cancer.

Clinical trial identification

NCT00878709.

Editorial acknowledgement

Lee Miller, Miller Medical Communications Ltd.

Legal entity responsible for the study

Puma Biotechnology Inc.

Funding

Puma Biotechnology Inc.

Disclosure

B. Moy, I. Gore: Research grant/Funding (institution): Puma Biotechnology Inc. R.P. Bryce, F. Xu, A. Wong: Shareholder/Stockholder/Stock options, Full/Part-time employment: Puma Biotechnology Inc. F.A. Holmes: Travel/Accommodation/Expenses: Puma Biotechnology Inc. All other authors have declared no conflicts of interest.

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Presenter Of 1 Presentation

 On-Demand ePoster Display

45P - Long-term Efficacy of Neratinib in HER2-Positive Early-Stage Breast Cancer: Overall Survival and Central Nervous System Outcomes from the Phase 3 ExteNET Trial

Abstract

Background

Neratinib (Nerlynx®) is an irreversible pan-HER inhibitor that significantly improves invasive disease-free survival (iDFS) vs placebo as extended adjuvant therapy in HER2-positive (HER2+) early-stage breast cancer (eBC) after trastuzumab-based therapy. The phase III ExteNET trial (NCT00878709) showed an absolute iDFS benefit of 2.5% and distant disease-free survival benefit of 1.7% with neratinib after 5 years’ follow-up. The brain is a common first site of metastasis after HER2-directed adjuvant therapy for eBC. To date, no HER2-directed therapies have prevented central nervous system (CNS) metastases in this setting.

Methods

Women with HER2+ eBC who had completed adjuvant therapy (± neoadjuvant therapy) with trastuzumab + chemotherapy were randomized to oral neratinib 240 mg/d or placebo for 1y. OS was analyzed after 248 events (powered for the ITT population). CNS outcomes: cumulative incidence of CNS recurrences (time from randomization to CNS recurrence as first distant recurrence); CNS disease-free survival (CNS-DFS, time from randomization to any CNS recurrence or death from any cause). Cut-off dates: 5y (Mar 2017); OS (Jul 2019).

Results

2840 patients were randomized (1420 per group). After a median follow-up of 8.1y, 8y OS rates were 90.1% (95% CI 88.3‒91.6) for neratinib and 90.2% (95% CI 88.4‒91.7) for placebo (absolute difference –0.1%; stratified HR=0.95; 95% CI 0.75‒1.21; p=0.6914). At 5y, cumulative incidence of CNS recurrences was 1.3% (95% CI 0.8–2.1) with neratinib and 1.8% (95% CI 1.2–2.7) with placebo, and CNS-DFS rates were 97.5% (95% CI 96.4–98.3) and 96.4% (95% CI 95.2–97.4), respectively (HR=0.73; 95% CI 0.45–1.17). No new safety signals were reported.

Conclusions

There were fewer deaths with neratinib than placebo in ExteNET, but the results did not reach statistical significance. Long-term CNS outcomes at 5y were also improved with neratinib. Neratinib is the first HER2-directed agent to show a trend towards improved CNS outcomes in HER2+ eBC, providing further support for current NCCN guidelines that recommend neratinib-based therapy for brain metastases from HER2-positive breast cancer.

Clinical trial identification

NCT00878709.

Editorial acknowledgement

Lee Miller, Miller Medical Communications Ltd.

Legal entity responsible for the study

Puma Biotechnology Inc.

Funding

Puma Biotechnology Inc.

Disclosure

B. Moy, I. Gore: Research grant/Funding (institution): Puma Biotechnology Inc. R.P. Bryce, F. Xu, A. Wong: Shareholder/Stockholder/Stock options, Full/Part-time employment: Puma Biotechnology Inc. F.A. Holmes: Travel/Accommodation/Expenses: Puma Biotechnology Inc. All other authors have declared no conflicts of interest.

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