Sessions are scheduled in Singapore Time (SGT)
- Khalil Zaman (Lausanne, Switzerland)
- Ching-Hung Lin (Taipei City, Taiwan)
- Soo Chin Lee (Singapore, Singapore)
1MO - The fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in Chinese patients (pts) with HER2-positive early breast cancer (EBC): Primary analysis of the phase III, randomised FDChina study
- Zhimin Shao (Shanghai, China)
Abstract
Background
PH FDC SC was shown to be non-inferior to intravenous (IV) P and H in cycle 7 serum trough concentrations (Ctrough), with comparable total pathological complete response (tpCR) rates and safety profiles, in pts with HER2-positive EBC (FeDeriCa; NCT03493854). It is also less invasive, preferred by pts and reduces pt chair time. FDChina (NCT04024462) assesses (neo)adjuvant PH FDC SC in Chinese pts.
Methods
Pts with operable or locally advanced/inflammatory disease (stage II–IIIC; primary tumour >2cm/node-positive) were randomised 1:1 to four doxorubicin (60 mg/m2) + cyclophosphamide (600 mg/m2) cycles every 3 weeks (q3w), then four docetaxel (D; 75–100 mg/m2) cycles q3w. Pts received PH FDC SC (loading: 1200 mg P + 600 mg H; maintenance: 600 mg P + 600 mg H) or PH IV (loading: 840 mg/8 mg/kg; maintenance: 420 mg/6 mg/kg) q3w alongside D. Pts then had surgery before continuing anti-HER2 therapy for 14 cycles. Co-primary endpoints: cycle 7 P and H Ctrough. Secondary endpoints: tpCR, long-term efficacy, safety. Stratification factors: hormone receptor status, stage at presentation.
Results
Intention-to-treat population: 99 pts (PH FDC SC) vs 101 (PH IV). Safety and per protocol pharmacokinetic populations had 100 and 89 pts per arm. Baseline characteristics were balanced between arms. P and H cycle 7 geometric mean ratios (Ctrough SC/IV) were 1.07 (90% confidence interval [CI]: 0.99–1.15) and 1.55 (1.44–1.67), with the lower limit exceeding the prespecified non-inferiority margin (0.8). tpCR rates were 55.6% (95% CI: 45.2–65.6) vs 56.4% (46.2–66.3) in the PH FDC SC vs PH IV arms, respectively. Grade ≥3 AEs occurred in 72% vs 69% of pts; injection/administration-related reactions within 24 hrs in 14% vs 12%; serious AEs in 18% vs 19%; fatal AEs in 1% (cardiac) vs 0. Incidence of anaphylaxis/hypersensitivity was 4% vs 1% and diarrhoea 27% vs 39% (both were mostly low grade).
Conclusions
FDChina met its co-primary endpoints: PH FDC SC P and H cycle 7 Ctrough were non-inferior to those for PH IV. tpCR rates were comparable between arms. No new safety signals were identified. This suggests PH FDC SC may be a viable treatment option for Chinese pts.
Clinical trial identification
NCT04024462.
Editorial acknowledgement
Research support in the form of third-party writing assistance for this abstract, furnished by Katie Wilson, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
Z. Shao, T. Huang, Z. Fan, Y. Wang, X. Yan, H. Yang, S. Wang, D. Pang, H. Li, H. Wang, C. Geng, L. Huang: Financial Interests, Institutional, Funding, Research funding, Investigator fees for this study: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. A. Siddiqui: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. B. Wang: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. B. Xie: Financial Interests, Personal, Full or part-time Employment, Prior full-time employment; left Roche on 22 June 2022: Roche (China) Holding Co. Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. G. Sun: Financial Interests, Personal, Full or part-time Employment: Roche (China) Holding Co. Ltd.; Financial Interests, Personal, Stocks/Shares, Owns stocks in Roche: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. E. Restuccia: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.
2MO - Final analysis of the phase III randomized clinical trial, comparing HD201 vs referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting
- Xavier Pivot (Strasbourg, France)
Abstract
Background
TROIKA trial previously demonstrated equivalence in terms of total pathological complete response (pCR) after neoadjuvant treatment between HD201 and referent trastuzumab. All secondary objectives and secondary endpoints were in line with the result of the primary endpoint. The objective was to compare survival outcomes and safety in patients treated by HD201 or referent trastuzumab in the TROIKA trial.
Methods
This study included 502 patients with ERBB2-positive early breast cancer treated with either HD201 or referent trastuzumab, across 70 centers in 12 countries in Western and Eastern Europe and Asia. This analysis was performed after all patients completed the study, at a median follow up of 37.7 months (Q1-Q3, 37.3-38.1 months). Eligible patients received 4 cycles of docetaxel, 75 mg/m2, followed by 4 cycles of epirubicin, 75 mg/m2, and cyclophosphamide, 500 mg/m2 with either HD201 or referent trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in the neoadjuvant setting and then, 10 cycles of HD201 or referent trastuzumab after surgery, according to their initial randomization. Event-free survival (EFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Hazard ratios (HR) were estimated by Cox proportional hazards regression. Adverse events (AEs) were graded per standard criteria.
Results
A total of 474 (94.2%) patients were eligible for inclusion in the per-protocol set. In this population, the 3-year EFS rates were 85.6% (95%CI: 80.28 - 89.52) and 84.9% (95%CI: 79.54 - 88.88) in HD201 and referent trastuzumab groups, respectively (Log rank p = 0.938) (HR 1.02, 95%CI: 0.63 - 1.63; p = 0.945). The 3-year OS rates were comparable for HD201 (95.6%; 95%CI: 91.90 - 97.59) and referent trastuzumab treatment groups (96.0%, 95%CI: 92.45 - 97.90) (log rank p = 0.606). During the post-treatment follow up period, AEs were reported for 64 (27.4%) and 72 (29.8%) patients in the HD201 and the referent trastuzumab groups respectively and no serious event was related to study treatment.
Conclusions
This final analysis of the TROIKA trial further confirms the comparable efficacy and safety of HD201 and referent trastuzumab.
Clinical trial identification
NCT03013504.
Legal entity responsible for the study
Prestige Biopharma Limited.
Funding
Prestige Biopharma Limited.
Disclosure
J. Kim, S. Pradhan, L. Jaison, P. Feyaerts: Financial Interests, Institutional, Full or part-time Employment: Prestige Biopharma Limited. All other authors have declared no conflicts of interest.
Invited Discussant 1MO and 2MO
- Ching-Hung Lin (Taipei City, Taiwan)
Q&A and discussion
- Khalil Zaman (Lausanne, Switzerland)
3MO - Patient-reported outcomes (PROs) of Chinese patients (pts) in monarchE: Abemaciclib plus endocrine therapy (ET) in adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (EBC)
- Qingyuan Zhang (Harbin, China)
Abstract
Background
Adjuvant abemaciclib (CDK4 & 6 inhibitor) plus ET demonstrated clinically meaningful improvement in invasive disease-free survival among Chinese pts with HR+, HER2-, node-positive, high-risk EBC in the monarchE phase III study. Here, we present data on PROs of Chinese pts at primary outcome analysis.
Methods
495 Chinese pts in safety population were included in PROs evaluation (abemaciclib + ET arm: 259; ET arm: 236). Health-related quality-of-life (FACT-B), ET symptoms (FACT-ES, 2 cognitive/3 bladder FACIT items), fatigue (FACIT-Fatigue) and symptom burden (FACT-B GP5) were assessed at randomization (baseline), 3/6/12/18/24 months on treatment and follow-up. Exploratory analyses assessed items reflecting common adverse events (AEs; diarrhea, fatigue, arthralgia, hot flushes), including frequency of scores for FACT-ES C5 “I have diarrhea”, and FACT-B GP5 “bothered by treatment side effect”. A mixed effect model for repeated measures (MMRM) compared summary and item scores by treatment arm. For the summary scores, a minimally important difference (MID) was defined as an effect size of a half standard deviation at baseline. For the item scores, a change of 1 was deemed meaningful.
Results
More than 90% of pts completed the baseline and at least one postbaseline PRO questionnaires. The MMRM analysis showed numerically similar results for all summary scores and items scores between two arms, and the changes from baseline, except diarrhea, did not reach MID in both arms at each visit. Change from baseline for diarrhea was ≤1.12 for pts receiving abemaciclib and ≤0 for ET only. From 3 months onwards, most pts who experienced diarrhea in the abemaciclib arm reported having diarrhea “a little bit” or “somewhat”. The frequency of diarrhea decreased after discontinuation of abemaciclib. Most pts in both arms reported being bothered “a little bit” or “not at all” by treatment side effect.
Conclusions
The addition of abemaciclib to ET did not result in notable differences in overall PROs, suggesting a tolerable profile for abemaciclib in Chinese EBC pts. Increased frequency of diarrhea was consistent with the known manageable, reversible AE profile.
Clinical trial identification
NCT03155997.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
Y. Yang, C. Qian: Financial Interests, Personal and Institutional, Full or part-time Employment: Eli Lilly and Company. All other authors have declared no conflicts of interest.
21MO - Primary results of a China bridging, phase II randomized study of initial endocrine therapy (ET) ± ribociclib (RIB) in pre- & postmenopausal Chinese women with HR+/HER2– ABC
- Zhimin Shao (Shanghai, China)
Abstract
Background
MONALEESA (ML)-2 and -7 enrolled postmenopausal (postM) and premenopausal (preM) patients (pts) with HR+/HER2− ABC, respectively, to initial RIB + ET treatment. Both demonstrated a statistically significant PFS and OS benefit in the ITT populations, with similar trends in the Asian subgroups. Specifically, regarding PFS in the Asian subgroups, RIB + ET had an HR of 0.39 (0.17-0.91) in ML-2 (n=51; median follow-up 15.3 mo) and ET had an HR of 0.40 (0.26-0.63) in ML-7 (n=198; median follow-up 19.2 mo). Here we report the primary results of a phase II bridging study of initial ET ± RIB in postM and preM pts from mainland China with HR+/HER2– ABC.
Methods
Pts were randomized 1:1; postM received letrozole (LET) + RIB or placebo (PBO) and preM received NSAI + goserelin + RIB or PBO. Primary endpoint was PFS (local assessment based on RECIST 1.1 criteria). The study was not powered to show statistical significance; it was adequately sized to show consistency of PFS of RIB + ET vs ET in Chinese populations compared to ML-2 and ML-7. Secondary endpoints included PK, OS, ORR, and safety.
Results
As of 15 April 2022, 77 and 77 postM pts and 79 and 77 preM pts were treated with RIB or PBO, respectively. Median follow-up was 34.7 mo for both groups. Baseline characteristics were generally balanced between arms within the cohorts. In the postM cohort, mPFS was not reached with RIB vs 18.5 mo with PBO (HR 0.400; 95% CI 0.258-0.618). In the preM cohort, the median PFS was 27.6 vs 14.7 mo (HR 0.672; 95% CI 0.448-1.009) for RIB vs PBO. ORR was higher for RIB in both postM and preM pts (Table); OS was not mature. The adverse event profile was consistent with what is known for ET ± RIB; the tolerability is consistent with ML-2 and -7 with no new findings.
Conclusions
Along with the results of the ML studies, this bridging study demonstrates the consistent efficacy benefit and well-tolerated safety profile of RIB + ET in Chinese pts. aMeasurable disease.
Parameter PostM PreM RIB + LET n=77 PBO + LET n=77 RIB + NSAI + goserelin n=79 PBO + NSAI + goserelin n=77 Treatment ongoing, n 35 11 27 14 PFS, median, mo Not reached 18.5 27.6 14.7 HR (95% CI) 0.400 (0.258-0.618) 0.672 (0.448-1.009) ORR, % (95% CI)a 60.3 (48.1-71.5) 49.3 (37.2-61.4) 53.6 (41.2-65.7) 38.5 (26.7-51.4)
Clinical trial identification
NCT03671330.
Editorial acknowledgement
Medical writing support was provided by Chris Carter at MediTech Media, funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
Y. Bai, K. Amin, P. Deshpande, Y. Bi: Financial Interests, Personal, Full or part-time Employment: Novartis. All other authors have declared no conflicts of interest.
22MO - Efficacy and safety of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer (mTNBC) by baseline HER2 expression level: Subgroup analysis from a phase IIb trial
- Fei Ma (Beijing, China)
Abstract
Background
About 30-40% of mTNBC patients (pts) have tumors with HER2 low expression, which might be a potential target of some novel anti-HER2 agents. Sacituzumab govitecan (SG), a novel Trop2-targeted antibody-drug conjugate, has been approved for second line onwards mTNBC treatment by Singapore and NMPA recently. To better understand the role of SG in the treatment of Chinese mTNBC with different HER2 expression level, subgroup data of EVER-132-001 were analyzed.
Methods
EVER-132-001 is a multicenter, single-arm, Phase IIb study of SG in Chinese pts with mTNBC who received at least two prior systemic treatments. In this subgroup analysis, HER2 status of the most recent tumor biopsy tissue was evaluated by immunohistochemistry [IHC] and Fluorescence in situ hybridization [FISH] locally. Pts were divided into 2 subgroups: HER2-neg (IHC 0) and HER2-low (IHC 1+, or IHC 2+ and FISH negative). Efficacy and safety of SG across subgroups were analyzed and reported.
Results
Of the 80 mTNBC pts enrolled, there were 43 reported HER2-neg and 37 HER2-low (IHC 1+, n=20). Demographics, baseline disease characteristics and prior anticancer treatments were generally balanced across the two subgroups. The median number of prior systemic therapies was 4 in both subgroups. According to Independent Review Committee assessment, objective response rate was 41.9% (95% confidence interval [CI] 27.01-57.87) in HER2-neg group and 35.1% (95% CI 20.21-52.54) in HER2-low group, and clinical benefit rate was 46.5% (95% CI 31.18-62.35) and 40.5% (95% CI 24.75-57.90), respectively. Median progression free survival was 6.9 months (95% CI 4.21-NA) in HER2-neg and 5.5 months (95% CI 2.83-NA) in HER2-low. SG-related CTCAE Grade ≥3 treatment-emergent adverse events reported were similar (69.8% vs 73.0%), and the most common ones both were neutrophil count decreased (62.8% vs 62.2%), white blood cell count decreased (44.2% vs 54.1%), and anemia (23.3% vs 18.9%).
Conclusions
SG showed comparable anti-tumor activity in both HER2-neg and HER2-low subgroups of later line Chinese mTNBC pts. The safety profile was consistent across two subgroups and both manageable.
Clinical trial identification
NCT04454437, First posted: July 1, 2020.
Legal entity responsible for the study
Everest Medicines.
Funding
Everest Medicines.
Disclosure
X.J. Cong, N. Wang, C. Xu, J.J. Chen: Financial Interests, Personal, Other, employee: Everest Medicines. All other authors have declared no conflicts of interest.
Invited Discussant 3MO, 21MO and 22MO
- Soo Chin Lee (Singapore, Singapore)
Q&A and discussion
- Khalil Zaman (Lausanne, Switzerland)
4MO - Prognostic implication of 21-gene expression assay in luminal B type hormone receptor-positive breast cancer patients younger than 40 years
- Jaewon Hyung (Seoul, Korea, Republic of)
Abstract
Background
Recurrence score (RS) based on 21-gene expression assay is widely used to evaluate prognosis and potential benefits of adjuvant chemotherapy (AC) for hormone-receptor positive (HR+) breast cancer (BC) patients (pts). In this study, we investigated clinical significance of RS in premenopausal HR+ BC pts.
Methods
HR+ BC pts with age < 50 years at diagnosis who had at least 3 years of follow-up duration from surgery and had 21-gene expression assay in Asan Medical Center, Seoul, Korea, between June 2005 to July 2018 were included. Recurrence-free survival (RFS) by STEEP version 2.0 was compared according to the RS and other clinicopathologic variables.
Results
Among total 567 pts included in this analysis, 117 pts (20.6%) had age < 40 years and 238 pts (42.0%) had luminal B type BC (LB) by 4-IHC, 85 pts (15.0%) had RS > 25, 301 pts (53.8%) had high clinical risk BC as defined by tumor size, lymph node and histologic grade and 92 pts (16.2%) had AC. On univariate analysis, pts with RS > 25 showed poor RFS (log-rank, p = 0.007). Also, pts with age < 40 years (log-rank, p = 0.008), high clinical risk (log-rank, p = 0.030) and LB (log-rank, p = 0.002) had poor RFS. On multivariate analysis, age < 40 years and LB were associated with significantly poor RFS with HR of 2.49 (95% CI 1.16-5.36, p = 0.020) and 2.59 (95% CI 1.11-6.04, p = 0.028), respectively while RS > 25 was not associated with RFS. When compared according to age group (< 40 years vs. 40 years) and luminal types (luminal A (LA) vs. LB), pts with age < 40 years and LB showed significantly poor RFS (HR 4.52, [95% CI 2.08-9.84], p < 0.001) compared to pts with age 40 years or LA. Pts with < 40 years with LB had higher proportion of pts who received AC (35.0% vs. 14.0%, p < 0.001) compared to pts with age 40 years or LA. While RS > 25 was associated with poor RFS among pts with age 40 years or LA (HR 3.20, [95% CI 1.20-8.53], p = 0.020), RS > 25 was not associated with RFS in pts with age < 40 years and LB (HR 1.31, [95% CI 0.34-5.10], p = 0.699).
Conclusions
The RS alone was not prognostic among premenopausal HR+ BC pts especially with age < 40 years and LB, which showed significantly poor RFS compared to pts with age 40 years or LA despite of higher proportion of pts who received AC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
5MO - Subtype-dependent loco-regional recurrence patterns in different subtypes of breast cancer: A retrospective analysis of 16,462 patients over 10 years of follow-up
- Jong-Ho Cheun (Seoul, Korea, Republic of)
Abstract
Background
While numerous studies have consistently reported that the molecular subtypes of breast cancer are associated with different patterns of distant metastasis, few studies have investigated the impact of molecular subtypes on loco-regional recurrence. We retrospectively investigated the patterns of loco-regional recurrence in a large cohort.
Methods
We reviewed the clinical records of all patients who underwent breast cancer surgery between January 2000 and December 2018 in a single institution and investigated the ipsilateral breast cancer recurrence (IBTR), regional recurrence (RR), and contralateral breast cancer (CBC) events. Tumor subtypes were sub-grouped according to hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status.
Results
A total of 16,462 patients were included in the analysis. For all patients, the ten-year IBTR-, RR- and CBC survival rate was 4.1%, 3.9% and 3.5%, respectively. On the log-rank test, HR-/HER+ tumors showed the worst IBTR-free survival rate (p<0.001), while HR-/HER2- subtype showed the worst RR- and CBC-free survival rate among all subtypes (p<0.001). Regarding annual recurrence patterns, the IBTR pattern of HR-/HER2+ and HR-/HER- subtypes showed double-peaks, while HR+/HER2- tumors showed a steadily increasing pattern without distinguishable peaks. Additionally, the HR+/HER2- subtype seems to have a steady RR pattern, while other subtypes showed the highest RR incidence at one year following surgery before gradually decreasing. Lastly, the annual recurrence rate of CBC showed gradually increasing tendencies for all subtypes, and the HR-/HER2- subtype showed a highest CBC rate for ten years. Younger patients had more evident difference in IBTR, RR, and CBC pattern between subtypes than elderly.
Conclusions
Loco-regional recurrence occurs with different patterns according to BC subtypes. The guidelines should consider the difference in loco-regional recurrence patterns according to tumor subtypes and recommend tailored surveillance strategies, especially for young patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
W. Han, H. Lee: Non-Financial Interests, Personal, Stocks/Shares: DCGen. All other authors have declared no conflicts of interest.
Invited Discussant 4MO and 5MO
- Khalil Zaman (Lausanne, Switzerland)
Q&A and discussion
- Khalil Zaman (Lausanne, Switzerland)