K. Jung (Seoul, Korea, Republic of)

Asan Medical Center

Author Of 3 Presentations

 On-Demand ePoster Display

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.

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%

Safety population *Related cardiac failure †Clinically significant LVEF drops: 1% of pts per arm.

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.

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103P - Long-term results and bone-protective effect of everolimus added to letrozole and ovarian function suppression for premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer: an updated analysis of the LEO study

Abstract

Background

In phase II LEO study, everolimus (EVE) plus letrozole (LET) with ovarian suppression resulted in longer progression-free survival (PFS) in tamoxifen-exposed premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer with visceral metastases. Here, we report an updated survival for the LEO study, along with the results of exploratory analyses on bone turnover marker changes and bone-specific progressive disease.

Methods

Patients who were exposed to or progressed on tamoxifen as adjuvant or palliative treatment were randomly assigned (2:1) to the EVE (leuprorelin+LET+EVE) or LET arm (leuprorelin+LET).

Results

With a median follow-up of 51 months, Median PFS was 17.5 months in EVE arm and 13.8 months in LET arm (p=0.245). PFS favored EVE arm in patients with baseline visceral metastases (median PFS, 16.4 vs 9.5 months, p=0.040), and patients with bone metastases (median PFS, 17.1 vs 10.9, p=0.003). No differences in the OS were observed (median OS, 48.3 vs. 50.8 months, p=0.948). One-year cumulative incidence of bone-specific disease progression was 6.0% in EVE arm, and 23.4% in LET arm (Hazard ratio 0.26, p<0.001). Bone markers at 6 and 12 weeks after treatment decreased in EVE arm, whereas they were increased or stationary in LET arm. Skeletal-related events occurred 6.5% and 11.1% of the patients in the EVE and LET arm, respectively.

Conclusions

EVE plus LET with ovarian-suppression prolonged PFS in patients with baseline visceral or bone metastases and offered bone-protective effect in the overall study population. However, these clinical benefits were not translated into an OS benefit.

Clinical trial identification

NCT02344550 Original release date: 31 December 2020.

Legal entity responsible for the study

The authors.

Funding

Novartis and Dongkook Pharma Co, Ltd.

Disclosure

K.H. Jung: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Novartis; Honoraria (self): Takeda. J.H. Sohn: Research grant/Funding (self): MSD; Research grant/Funding (self): Roche; Research grant/Funding (self): Novartis; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Lilly; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Bayer; Research grant/Funding (self): GSK; Research grant/Funding (self): CONTESSA; Research grant/Funding (self): Daiichi Sankyo. K.S. Lee: Honoraria (self): Roche; Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): MSD; Non-remunerated activity/ies, drug supply: Dong-A ST. S-B. Kim: Research grant/Funding (self): Novartis; Research grant/Funding (self): Sanofi-Aventis; Research grant/Funding (institution): DongKook Pharm Co.; Advisory/Consultancy: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Advisory/Consultancy: Enzychem; Advisory/Consultancy: Dae Hwa Pharmaceutical Co. Ltd; Advisory/Consultancy: ISU Abxis; Advisory/Consultancy: Daiichi Sankyo. All other authors have declared no conflicts of interest.

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119P - Clinical efficacy of everolimus and CDK4/6 inhibitors in hormone receptor-positive, HER2-negative metastatic breast cancer by treatment sequence

Abstract

Background

In hormone receptor-positive, HER2-negative metastatic breast cancer (HR+ HER2- MBC), cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and everolimus (EVE) in combination with endocrine treatment comprise the mainstay of treatment. This study aims to evaluate the clinical outcomes by treatment sequence between the two regimens.

Methods

HR+ HER2- MBC patients treated with both CDK4/6 inhibitor and EVE from Jan 2014 to Nov 2020 were retrospectively identified and analyzed.

Results

A total of 88 patients were included in the study. Among those, 51 received CDK4/6i before EVE (C→E group) and 37 received EVE before CDK4/6i (E→C group) in combination with endocrine treatment. More patients in E→C group had endocrine resistance (13.7% vs. 40.5%), had experienced palliative chemotherapy (7.8% vs. 40.5%), and were heavily treated (treated as ≥3rd line, 5.9% vs. 40.5%). The median overall survival was 46.8 months in the C→E group and 38.9 months in the E→C group (p=0.151). The median composite progression-free survival, defined as the time from the start of preceding regimen to the disease progression on the following regimen or death, was 24.8 months vs. 21.8 months (p=0.681). The median PFS2/PFS1 ratio did not differ significantly between groups (0.5 in the C→E group, 0.6 in the E→C group, p=0.775). Ten patients (11.4%) discontinued EVE and 2 patients (2.3%) discontinued CDK4/6i during treatment.

Conclusions

Given that prior CDK4/6i was not associated with worse treatment outcomes to EVE, EVE-based regimen could be considered one of the reasonable treatment options after CDK4/6i.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

K.H. Jung: Honoraria (self), outside this work: AstraZeneca; Honoraria (self), outside this work: Roche; Honoraria (self), outside this work: Celgene; Honoraria (self), outside this work: Novartis; Honoraria (self), outside this work: Takeda. S-B. Kim: Advisory/Consultancy, Research grant/Funding (self), outside this work: Novartis; Research grant/Funding (self), outside this work: Sanofi-Aventis; Research grant/Funding (self), outside this work: DongKook Pharm Co.; Advisory/Consultancy, outside this work: AstraZeneca; Advisory/Consultancy, outside this work: Lilly; Advisory/Consultancy, outside this work: Enzychem; Advisory/Consultancy, outside this work: Dae Hwa Pharmaceutical Co. Ltd.; Advisory/Consultancy, outside this work: ISU Abxis; Advisory/Consultancy, outside this work: Daiichi Sankyo. All other authors have declared no conflicts of interest.

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