- Sung-Bae Kim (Seoul, KR)
- Mastura Md Yusof (Kuala Lumpur, MY)
- Jason Pitt (Singapore, SG)
LBA2 - Analytical and clinical validation of a ctDNA-based assay for multi-cancer detection
- Le Son Tran (Ho Chi Minh City, VN)
- Le Son Tran (Ho Chi Minh City, VN)
- Luu Hong Dang Nguyen (Ho Chi Minh City, VN)
- Thi Hue Hanh Nguyen (Ho Chi Minh City, VN)
Abstract
Background
Early cancer detection is essential to achieve better treatment outcomes and reduce mortality. However, most current screening methods test for a single cancer type or some of them are invasive, resulting in a low accessibility rate. To overcome such clinical challenges, we previously developed a multimodal liquid biopsy-based assay named Screening for the Presence of Tumor by Methylation And Size (SPOT-MAS) to detect the five most common types of cancer in Vietnam (liver, breast, colorectal, gastric, and lung cancer). Herein, we launched a large-scale study, named K-DETEK, to assess the feasibility and clinical performance of SPOT-MAS in a multi-center clinical trial setting.
Methods
A prospective cohort study (ClinicalTrials.gov identifier: NCT05227261) was conducted at 13 major hospitals and one research institute in Vietnam. Our study recruited asymptomatic participants aged 40 years or older and followed up for 6 and 12 months. Analytical sensitivity of our assay was assessed by using our healthy and cancer-standard samples with known tumor fraction. The clinical performance was assessed by computing the positive predictive value (PPV), the negative predictive value (NPV) and accuracy in detecting tumor tissue-of-origin (TOO).
Results
We established a clinical limit of detection (LOD) value of 0.038 (95% CI:0.035-0.042) and did not observe any noticeable impact of potential inferences (hemolysis rate, genomic DNA) on our assay performance. Furthermore, our analysis of 9,024 eligible participants demonstrated its ability to detect cancers in asymptomatic individuals with a PPV of 57.14%, a NPV of 99.92% and an accuracy of 80.00% in detecting tumor location.
Conclusions
Our study provides analytical and clinical evidence to support SPOT-MAS as a multi-cancer blood test for early detection in a low- and middle-income country, especially in Vietnam, where a nationwide cancer screening program is urgently needed but currently not available. Beyond detecting cancer signals, our test predicted the tumor location, allowing clinicians to fast-track the follow-up diagnostic and guide any necessary treatment.
Clinical trial identification
NCT05227261.
Legal entity responsible for the study
The study was reviewed and approved by the institutional ethics committee of the University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam (approval number: 192/HĐĐĐ-ĐHYD).
Funding
Gene Solutions JSC.
Disclosure
L.S. Tran: Financial Interests, Institutional, Advisory Board: Gene Solutions. All other authors have declared no conflicts of interest.
1MO - Image biomarker discovery from DCE-MRI for identifying responders of MK-2206 on early-stage breast cancer patients: A secondary radio-genomics analysis of I-SPY2 trial
- Jiang Zhang (Kowloon, HK)
- Jiang Zhang (Kowloon, HK)
- Xinzhi Teng (Kowloon, HK)
- Qingpei Lai (Kowloon, HK)
- Xinyu Zhang (Kowloon, HK)
- Xinyu Fan (Kowloon, HK)
- Ta Zhou (Kowloon, HK)
- Yu-hua Huang (Kowloon, HK)
- Cai Jing (Kowloon, HK)
Abstract
Background
The pan-Akt inhibitor MK-2206 has shown promising results in improving the pathological complete response (pCR) rate in high-risk early-stage breast cancer in the I-SPY2 trial. However, a considerable portion of patients does not respond to MK-2206 in addition to standard therapy. This study aimed to discover image biomarkers from DCE-MRI images that can further select responders of MK-2206.
Methods
A total of 1104 patients from the I-SPY2 trail were enrolled in this study. DCE-MRI images were collected from the 92 patients in the MK-2206 arm and 209 in the control arm for biomarker discovery. Image biomarkers, extracted from pre-treatment DCE-MR images within the functional tumor volume, were identified with high repeatable/reproducible and significant associations between pCR and biomarker-treatment interaction. Treatment sensitivity of image biomarker-defined subtypes were quantified with odds ratio (OR). Bayesian logistic regression was used to estimate the pCR rates of the MK-2206 and control arm. An exploration of differentially expressed proteins/genes and biological pathways was also conducted.
Results
One reliable image biomarker, glcm_SumSquares (GLCM_SS), was found to be predictive of treatment response. The positive group (GLCM_SS+) was highly sensitive to MK-2206 in the entire discovery cohort and specific subgroups (HER2-, HR-, HER2-/HR-, and MammaPrint (MP)2) with ORs ranging from 5.50 to 18.13 (P<0.001). With the image biomarker, the mean estimated pCR rates of the MK-2206 arm increased significantly from 38% to 56% (P=0.022) in the entire discovery cohort, 30% to 46% (P=0.023) in the HER2- subtype, 49% to 71% (P=0.005) in the HR- subtype, 39% to 63% (P=0.009) in the HER2-/HR- subtype, and 44% to 64% (P=0.005) in the MP2 subtype. GLCM_SS+ was also associated with overexpression of total PTEN protein and enriched by immune-related pathways.
Conclusions
An image biomarker, GLCM_SS, has been identified to be able to select the responders of AKT-inhibitor MK-2206. GLCM_SS+ also showed distinct gene profiles enriched in immune signaling. Further experiments are planned to verify the radiogenomics association with GLCM_SS+ sensitivity to MK-2206.
Legal entity responsible for the study
Jing Cai.
Funding
Mainland-Hong Kong Joint Funding Scheme (MHKJFS) (MHP/005/20); Shenzhen Basic Research Program (JCYJ20210324130209023); Project of Strategic Importance Fund (P0035421) and Projects of RISA (P0043001) from The Hong Kong Polytechnic University; Health and Medical Research Fund (HMRF 09200576), the Health Bureau, The Government of the Hong Kong Special Administrative Region.
Disclosure
All authors have declared no conflicts of interest.
56MO - Landscape of ESR1 mutations in advanced breast cancer using circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in Asia and Middle East (AME)
- Shaheenah Dawood (Dubai, AE)
- Shaheenah Dawood (Dubai, AE)
- Marwan Al Akasheh (Amman, JO)
- Tamar Peretz-Yablonski (Jerusalem, IL)
- Noa E. Ben-Baruch (Rehovot, IL)
- Nippun Sandhir (Singapore, SG)
- Suyog S. Jain (Singapore, SG)
Abstract
Background
Endocrine therapy, including aromatase inhibitors (AI), is the foundation of treatment for patients (pts) with estrogen receptor-positive (ER+) advanced breast cancer (ABC). Mutations in
Methods
We reviewed results of Guardant360 (Guardant Health, Inc) ordered for patients with ABC in AME as part of routine clinical practice through December 2022. This comprehensive genomic profiling assay identifies single-nucleotide variants, insertions and deletions, fusions, and amplifications. All samples were analyzed by a single CLIA-certified and CAP-accredited laboratory in California. Prescribing physicians did not routinely provide tumor ER status or treatment history when ordering ctDNA NGS.
Results
Among 898 samples analyzed, ctDNA was detected in 796 (88.65%), representing 772 unique ABC pts, all women. Median pt age was 56 years (range 27-87). There were 309
Conclusions
Comprehensive ctDNA NGS can identify
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Dawood: Financial Interests, Personal, Advisory Role: Guardant Health. N. Sandhir, S.S. Jain: Financial Interests, Personal, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.
Invited Discussant one LBA2, 1MO and 56MO
- Sung-Bae Kim (Seoul, KR)
- Sung-Bae Kim (Seoul, KR)
Q&A and discussion
- All Speakers (Lugano, CH)
- All Speakers (Lugano, CH)
2MO - Multimodal data fusion enhanced precision neoadjuvant chemotherapy in breast cancer with a multi-task transformer-CNN-mixed learning
- Yunfang Yu (Guangzhou, CN)
- Yunfang Yu (Guangzhou, CN)
- Zifan He (Guangzhou, CN)
- Zehua Wang (Macau, CN)
- Ruichong Lin (Macau, CN)
- Tang Li (Guangzhou, CN)
- Zebang Zhang (Guangzhou, CN)
- Wei Ren (Guangzhou, CN)
- Luhui Mao (Guangzhou, CN)
- Herui Yao (Guangzhou, CN)
Abstract
Background
In medical practice, clinicians merge diverse information sources. While AI has the potential to aid healthcare professionals, its current ability to smoothly integrate various algorithms and diverse multimodal data is limited, posing a constraint on its practical utilization in clinical settings. The objective of this study is to leverage AI techniques that combine histopathology and clinical data to enhance the precision of neoadjuvant chemotherapy (NAC) in breast cancer management.
Methods
We retrospectively recruited 756 patients in the training cohort from the campus 1 of Sun Yat-sen Memorial Hospital (SYSMH), 560 in the validation cohort from the campus 2 of SYSMH. Additionally, 227 patients were included in the prospective test cohort for a blinded prospective validation. We developed a AI-pathology model comprising both CNN-based and Transformer-based feature extraction channels. Building upon the AI-pathology model, we devised an AI-multimodal model that fused pathological and clinical information. The study's endpoints were pathological complete response (pCR) and disease-free survival (DFS).
Results
A total of 1,598 patients were enrolled in this study. The AI-pathology model demonstrated favorable accuracy for pCR prediction in the training cohort (AUC 0.999), as well as in the validation and the prospective test cohorts (0.995, 0.981). Notably, the AI-multimodal model (AUC 0.999, 0.994 in the validation and prospective test cohorts) surpassed the AI-pathology model. Besides, Kaplan-Meier analysis showed that patients predicted by the AI-multimodal model to achieve a pCR had a favourable DFS compared with non-pcr patients (p<0.05). The combined visualization heatmap and single-cell analysis provided insights into decision-making processes, linking model predictions with the tumor microenvironment, particularly the infiltration and functional status of T cells and B cells.
Conclusions
The AI-multimodal model, integrating both pathological and clinical information, effectively predicted pCR and DFS in the context of NAC. Its high accuracy and robustness present a novel tool for guiding personalized breast cancer management based on pre-treatment pathological images.
Legal entity responsible for the study
The authors.
Funding
This study was supported by grants 2023YFE0204000 from National Key R&D Program of China, grants 82273204 and 81972471 from the National Natural Science Foundation of China, grant 2023A1515012412 and 2023A1515011214 GuangDong Basic and Applied Basic Research Foundation, grant 2023A03J0722, 202206010078 and 202201020574 from the Guangzhou Science and Technology Project, grant 2018007 from the Sun Yat-Sen University Clinical Research 5010 Program, grant SYS-C-201801 from the Sun Yat-Sen Clinical Research Cultivating Program, grant A2020558 from the Guangdong Medical Science and Technology Program, grant 7670020025 from Tencent Charity Foundation, grant YXQH202209 from the Scientific Research Launch Project of Sun Yat-sen Memorial Hospital.
Disclosure
All authors have declared no conflicts of interest.
3MO - Multimodal data fusion for improved risk stratification of breast cancer with multi-task 3D deep learning model: A multicenter study
- Wei Ren (Guangzhou, CN)
- Wei Ren (Guangzhou, CN)
- Yunfang Yu (Guangzhou, CN)
- Wenhao Ouyang (Guangzhou, CN)
- Luhui Mao (Guangzhou, CN)
- Qinyue Yao (Guang Zhou, CN)
- Yujie Tan (Guangzhou, CN)
- Zifan He (Guangzhou, CN)
- Tang Li (Guangzhou, CN)
- Zebang Zhang (Guangzhou, CN)
- Jin Wang (Guang Zhou, CN)
- Herui Yao (Guangzhou, CN)
Abstract
Background
Timely intervention and improved prognosis for breast cancer patients rely on early metastasis risk detection and accurate treatment predictions. This study aims to the amalgamation of artificial intelligence innovation and medical research by developing a novel multi-task 3D deep learning model with MRI-based multimodal data fusion.
Methods
This pioneering multicenter study involves 1,244 non-metastatic breast cancer patients, who were assigned into the training cohort (n = 456), internal validation cohort (n = 113), external testing cohort 1 (n = 432), and external testing cohort 2 (n = 198). An innovative multimodal approach integrating clinicopathological data with deep learning MRI insights yielded the multi-task 3D deep learning model (3D-MMR-model), which was developed for tumor segmentation and disease-free survival (DFS) prediction. The efficacy was demonstrated through tumor segmentation accuracy metrics and DFS prediction AUC values. Visualization techniques provided insight into decision-making processes, correlating model predictions with the tumor microenvironment.
Results
The 3D-MMR-model demonstrated a high degree of predictive accuracy and significant boost for DFS. The AUC for 4-year DFS prediction escalated to 0.98, 0.97, 0.90, and 0.93 within the training cohort, internal validation cohort, external testing cohort 1, and external testing cohort 2, respectively. Our multimodal model showcased significant distinctions in DFS between patients with high versus low risk scores (All
Conclusions
This study introduces a transformative approach to breast cancer prognosis, amalgamating imaging and clinical data for enhanced predictive accuracy, thus holding promise for personalized treatment strategies.
Legal entity responsible for the study
Sun Yat-sen Memorial Hospital of Sun Yat-sen University.
Funding
National Natural Science Foundation of China.
Disclosure
All authors have declared no conflicts of interest.
4MO - A prediction model for developing lymphedema in breast cancer patients receiving sentinel node biopsy
- Jin Young Byeon (Seoul, KR)
- Jin Young Byeon (Seoul, KR)
- IKBEOM Shin (Seoul, KR)
- Hawjeong Lee (Seoul, KR)
- Ji-jung Jung (Seoul, KR)
- Eunhye Kang (Seoul, KR)
- Hong-Kyu Kim (Seoul, KR)
- Han-Byoel Lee (Seoul, KR)
- Wonshik Han (Seoul, KR)
- Hyeong-Gon Moon (Seoul, KR)
Abstract
Background
While there are numerous studies describing the potential risk factors for developing ipsilateral lymphedema in breast cancer patients who receive axillary node dissection, the risk factors for lymphedema for patients receiving sentinel node biopsy only have not been clearly identified. The aim of this study is to identify risk factors for the postoperative lymphedema in breast cancer patients who underwent sentinel lymph node biopsy only.
Methods
Among the patients who underwent surgery for their breast cancer at Seoul National University Hospital from Jan 2017 to Dec 2020, the patients who received sentinel node biopsy only for their axillary staging were included for this retrospective study.
Results
In this study, we investigated factors associated with the development of lymphedema in a cohort of 5,051 patients. The median age of the patients was 52 years. During a median follow-up of 56.5 months, 49 patients (0.9%) developed ipsilateral lymphedema after surgery, with most cases occurring within the first three years. In multivariate analysis, obesity, radiation therapy, chemotherapy, and more than three sentinel nodes remained independent predictors of lymphedema. We developed a predictive model for lymphedema after sentinel node biopsy, incorporating radiation therapy (coefficient 0.756), chemotherapy (2.030), BMI of 30 or higher (1.390), and more than three sentinel nodes (1.813), with an AUC of 0.824. The model demonstrated a sensitivity of 87.8%, specificity of 66.8%, positive predictive value of 2.5%, and negative predictive value of 99.8%. Systemic chemotherapy was the most influential factor in the model, followed by the number of harvested lymph nodes. Based on these risk factors, patients were classified into four groups, with the high-risk group showing a 3.3% risk of lymphedema, while the low- and medium-low-risk groups had less than 1% risk.
Conclusions
Our study found a 1% risk of lymphedema in breast cancer patients undergoing sentinel node biopsy. We developed a predictive model for identifying high-risk patients, facilitating early intervention and enhancing patient care.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 2MO, 3MO and 4MO
- Jason Pitt (Singapore, SG)
- Jason Pitt (Singapore, SG)
Q&A and discussion
- All Speakers (Lugano, CH)
- All Speakers (Lugano, CH)
LBA3 - Phase III study of neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer (TNBC): KEYNOTE-522 Korean subgroup analysis
- Jin-Hee Ahn (Seoul, KR)
- Yeon Hee Park (Seoul, KR)
- Seock-Ah Im (Seoul, KR)
- Jin-Hee Ahn (Seoul, KR)
- Min Hwan Kim (Seoul, KR)
- Javier Cortés (Barcelona, ES)
- Rebecca A. Dent (Singapore, SG)
- Lajos Pusztai (New Heaven, US)
- Heather L. McArthur (Dallas, US)
- Sherko Kummel (Essen, DE)
- Carsten Denkert (Marburg, DE)
- Joyce O'Shaughnessy (Dallas, US)
- Marie-Ange Mouret-Reynier (Clermont-Ferrand, FR)
- Marta I. Ferreira (Porto, PT)
- Maria Gion Cortes (Madrid, ES)
- Jean-Francois Boileau (Montreal, CA)
- Rina Hui (Westmead, AU)
- Yalin Zhu (Washington, US)
- Wilbur Pan (Rahway, US)
- Valia V. Karantza (Rahway, US)
- Peter Schmid (London, GB)
Abstract
Background
KEYNOTE-522 (NCT03036488) is a global, phase 3, randomized, double-blind study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as neoadjuvant therapy followed by adjuvant pembro vs pbo for early-stage TNBC. Pembro-chemo/pembro demonstrated clinically meaningful and statistically significant improvements in pathologic complete response (pCR at IA2; 65% vs 51%;
Methods
Pts with previously untreated, nonmetastatic, centrally confirmed TNBC (T1c N1/N2 or T2–4 N0–N2 per AJCC) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or pbo, each with 4 cycles of paclitaxel + carboplatin, then with 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, pts received 9 cycles of adjuvant pembro or pbo. Dual primary endpoints were pCR (ypT0/Tis ypN0) and investigator-assessed EFS. Overall survival (OS) was a secondary endpoint. Adverse events (AEs) were graded per NCI CTCAE v4.0. No alpha was assigned to this post hoc exploratory subgroup analysis.
Results
A total of 86 pts were randomized (pembro-chemo/pembro, n = 56; pbo-chemo/pbo, n = 30). Median time from randomization to data cutoff (Mar 23, 2021) was 38.6 mo (range, 30.4–45.5). pCR (95% CI) was 68% (54%–80%) with pembro-chemo/pembro and 47% (28%–66%) with pbo-chemo/pbo. 4 (7%) and 10 pts (33%), respectively, had EFS events (HR, 0.19 [95% CI, 0.06–0.60]). 3-y EFS rates were 93% vs 70%; median EFS was not reached in either arm. 3-y OS rates were 98% vs 68%. Grade ≥3 treatment-related AEs (TRAEs) occurred in 82% of pts with pembro-chemo/pembro and 87% with pbo-chemo/pbo. No grade 5 TRAEs were reported.
Conclusions
Neoadjuvant pembro + chemo followed by adjuvant pembro led to improved efficacy vs pbo-chemo/pbo and manageable safety in pts with previously untreated, early-stage, nonmetastatic TNBC enrolled in KEYNOTE-522 in the Republic of Korea. Results are consistent with overall study population findings.
Clinical trial identification
NCT03036488.
Editorial acknowledgement
Medical writing assistance was provided by Susan Tyree, PhD, CMPP, of ICON plc (Blue Bell, PA, USA).
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
Y.H. Park: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Eisai, Roche, Daiichi Sankyo, MENARINI, Bixink, Everest, Novartis, Inc.; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, AstraZeneca, Novartis, Genome Insight, NGenBio, Roche. S. Im: Financial Interests, Personal, Advisory Role: AstraZeneca, Novartis, Roche/Genentech, Pfizer, Amgen, Hanmi, Lilly, GlaxoSmithKline, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Daiichi Sankyo; Financial Interests, Institutional, Research Funding: AstraZeneca, Pfizer, Roche/Genentech, Daewoong Pharmaceutical; Financial Interests, Personal, Other: Roche. M.H. Kim: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boryung Pharmaceutical, Celltrion, Daiichi Sankyo, Eisai, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Institutional, Research Funding: AstraZeneca, Boryung Pharmaceutical. J. Cortés: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Scorpion Therapeutics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, BridgeBio; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Daiichi Sankyo, AstraZeneca, Gilead, Steamline Therapeutics; Financial Interests, Institutional, Research Funding: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, Guardant Health, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Piqur Therapeutics, IQVIA, Queen Mary University of London, F. Hoffman-La Roche; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, Relative: Leuko; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Other, (1) Pharmaceutical Combinations of A Pi3k Inhibitor And A Microtubule Destabilizing Agent. Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde. WO 2014/199294 A. ISSUED and (2) Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Aleix Prat, Antonio Llombart, Javier Cortés.US 2019/ 0338368 A1. LICENSED: Patents. R.A. Dent: Financial Interests, Personal, Advisory Role: AstraZeneca, Eisai, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Eisai, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Roche. L. Pusztai: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, Novartis, Genentech, Eisai, Pieris, Immunomedics, Seattle Genetics, Almac, Syndax; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, Seattle Genetics; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, Novartis, Genentech, Eisai, Pieris, Immunomedics, Almac, Syndax, Seattle Genetics; Financial Interests, Personal, Other, Honoraria (self): Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, Novartis, Genentech, Eisai, Pieris, Immunomedics, Seattle Genetics, Almac, Syndax. H.L. McArthur: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Bristol Myers Squibb, Spectrum Pharm, Lilly, Amgen, Immunomedics, Pfizer, Genentech, AstraZeneca; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Bristol Myers Squibb; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Bristol Myers Squibb, Spectrum Pharm, Lilly, Amgen, Immunomedics, Pfizer, Genentech, AstraZeneca, Puma Biotechnology. S. Kummel: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting Fees: Roche; Genomic Health; Novartis; Amgen; Celgene; Daiichi Sankyo; AstraZeneca; Somatex; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Pfizer; PFM Medical; Lilly; Sonoscape; Financial Interests, Institutional, Research Funding: Roche, Somatex; Financial Interests, Personal, Ownership Interest, Minority ownership: WSG Study Group; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Daiichi Sankyo, Sonoscape. C. Denkert: Financial Interests, Personal, Other, Honoraria (Self): Teva, Novartis, Pfizer, Roche, Amgen; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Sividon (Myriad); Financial Interests, Personal, Other, Licensing/Royalties: VmScope. J. O'Shaughnessy: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bayer, BMS, Celgene, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre, Puma Biotechnology, Prime Oncology, Roche, Samsung Bioepis, Sanofi, Seagen, Syndax Pharmaceuticals, Sy. M. Mouret-Reynier: Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. M.I.R. Ferreira: Financial Interests, Institutional, Local PI: AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Taiho Oncology; Financial Interests, Institutional, Other, Sub-investigator: AstraZeneca, Daiichi Sankyo, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Roche; Non-Financial Interests, Personal, Member of Board of Directors, Board member (treasurer): Grupo de Estudos Oncológicos. M. Gion Cortes: Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. J. Boileau: Financial Interests, Personal, Other, Speaking honoraria: Roche, Novartis, Genomic Health, Pfizer, Allergan, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Advisory Board: Roche, Genomic Health, Nanostring Technologies, Pfizer, Lilly, Novartis, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Other, Travel support: Roche, GSK, Novartis, Pfizer, LifeCell; Financial Interests, Institutional, Research Funding: Roche, Novartis, Pfizer, AbbVie, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, RNA Diagnostics Inc., Lilly, Bristol Myers Squibb, Genomic Health. R. Hui: Financial Interests, Personal, Advisory Board, Received personal fees for advisory boards: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, BMS, Eisai, Eli Lilly, Merck KGaA, Novartis, Oncosec, Pfizer, Roche, Seagen; Financial Interests, Personal, Other, Speaker honoraria: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Roche; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, BMS, Corvus, Eli Lilly, Janssen, Novartis, Olema, Oncosec, Roche, Seagen. Y. Zhu, W. Pan, V.V. Karantza: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. P. Schmid: Financial Interests, Personal, Other, Has been a consultant to/received honoraria from: AstraZeneca, Bayer, Boehringer Ingelheim, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Puma, Roche, Eisai, Celgene; Financial Interests, Institutional, Research Funding: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Other, Spouse is Roche employee: Roche. All other authors have declared no conflicts of interest.
LBA6 - A phase II, single arm, open label, Simon two-stage study of pembrolizumab in metastatic HER2-negative breast cancer patients: Evaluation of impact of germline variants in APOBEC3B (AUROR)
- Gwo Fuang Ho (Kuala Lumpur, MY)
- Gwo Fuang Ho (Kuala Lumpur, MY)
- Soo Chin Lee (Singapore, SG)
- Jia Wern Pan (Subang Jaya, MY)
- Anita Z. Bustam (Kuala Lumpur, MY)
- Adlinda Alip (Kuala Lumpur, MY)
- Nur Fadhlina Bt Abdul Satar (Kuala Lumpur, MY)
- Marniza Saad (Kuala Lumpur, MY)
- Rozita Abdul Malik (Kuala Lumpur, MY)
- Siew Eng Lim (Singapore, SG)
- Samuel Ow (Singapore, SG)
- Natalie Y. Ngoi (Houston, US)
- Kian Boon Law (Shah Alam, MY)
- Yok Yong Toh (Kuala Lumpur, MY)
- Bawani Selvam (Subang Jaya, MY)
- Joanna Lim (Subang Jaya, MY)
- Soo-Hwang Teo (Subang Jaya, MY)
Abstract
Background
A common germline deletion polymorphism in the
Methods
Using DNA extracted from peripheral blood, germline APOBEC3B polymorphism status was determined using single tube PCR assay using one forward and two reverse primers flanking the deletion. In total, 146 patients were screened, and 92 patients (63%) were found to be either homozygous or heterozygous carriers. 44 subjects who received >= 1 but <=3 lines of therapy in a metastatic setting were enrolled and given pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W), with Objective Response Rate (ORR) using RECIST 1.1 as the primary study endpoint.
Results
The median age of patients was 58.1 years (range, 32.1–82.9), of whom 75.0% were Chinese, 18.2% Malay, 4.5% Indian and 2.3% other ethnicity, and 31 patients had ECOG 0 and 13 had ECOG 1. The median number of lines of therapy received by the patients were two lines (range, 1–3). The ORR was 20.4 % (95% CI: 8.5 – 32.4) in 40 evaluable patients, which included one complete response and eight partial responses, as determined by RECIST 1.1.. Of these 9 patients, at the time of this analysis, 3 are still ongoing treatment and 6 had a median duration of response of 8.8 months (range: 2.1 – 32.4). The median OS was 15.4 months (95% CI: 11.7–26.5), with a 6-month and 1-year OS rate of 81.1% (95% CI: 70.1–93.9) and 62.0% (95% CI: 47.7–80.5), respectively. Notably, whereas responses to checkpoint immunotherapy have been reported to be low in ER+ patients, in A3B carriers, we found similar trends in OS, PFS and ORR in both ER+ and ER- patients, which warrants further analysis. The treatment was well tolerated by patients, with 13 out of 40 subjects experiencing SAEs, of which only 1 (colitis) was related to the investigational product.
Conclusions
Single agent pembrolizumab demonstrated promising anti-tumour activity in germline A3Bdel carriers, who constitute almost two-thirds of Asian patients.
Clinical trial identification
NCT03989089.
Legal entity responsible for the study
University Malaya Medical Centre.
Funding
Merck Sharp & Dohme.
Disclosure
All authors have declared no conflicts of interest.
57MO - First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in HR+/HER2− advanced breast cancer (ABC): A post hoc analysis of Asian and non-Asian patients (pts) from the phase II RIGHT choice trial
- Govind Babu Kanakasetty (Bangalore, IN)
- Yoon-Sim Yap (Singapore, SG)
- Seock-Ah Im (Seoul, KR)
- Yen-Shen Lu (Taipei City, TW)
- Hamdy A. Azim (Giza, EG)
- Yesim Eralp (Istanbul, TR)
- Govind Babu Kanakasetty (Bangalore, IN)
- Hikmat Abdel-Razeq (Amman, JO)
- Lyudmila Zhukova (Moscow, RU)
- Astrid Thuerigen (Basel, CH)
- Teresa Delgar Alfaro (Basel, CH)
- Jiwen Wu (East Hanover, US)
- Melissa Gao (Basel, CH)
- Nagi S. El Saghir (Beirut, LB)
Abstract
Background
RIGHT Choice reported a statistically significant median progression-free survival (mPFS) benefit of ≈1 y with RIB + ET vs combo CT (24.0 vs 12.3 mo; HR, 0.54;
Methods
Pre- or perimenopausal pts with HR+/HER2− ABC and no prior systemic therapy for ABC were randomized to RIB + ET or investigator’s choice of combo CT (Table). Pts had ABC for which combo CT was clinically indicated by physician’s judgment (symptomatic visceral metastases, rapid disease progression/impending visceral compromise, or markedly symptomatic non-visceral disease).
Results
Pt characteristics between arms were balanced in the Asian (n=118) and non-Asian (n=104) subgroups. Similar characteristics were seen in Asian and non-Asian pts, with some differences in BMI (median, 23.7 vs 26.3 kg/m2) as well as the proportion with symptomatic non-visceral disease (7.6% vs 21.2%) and physician-assessed visceral crisis (69.5% vs 32.7%). The PFS benefit with RIB + ET vs CT was 15.0 mo (mPFS, 25.2 vs 10.2 mo; HR, 0.43) in Asian pts and 8.3 mo (21.1 vs 12.8 mo; HR, 0.75) in non-Asian pts. In both groups, the median time to treatment (tx) failure (mTTF) was longer and the 3-mo tx failure rate (TFR) was lower with RIB + ET vs CT. In Asian pts, the overall response rate (ORR) was higher with RIB + ET than CT, with similar clinical benefit rate (CBR) and median time to response (mTTR) in both arms. In non-Asian pts, the ORR and CBR were similar in both arms, with longer mTTR for RIB + ET vs CT. The safety profile in the subgroups was consistent with that of the overall pt population.
Conclusions
This post hoc analysis confirmed a clinically meaningful PFS benefit with 1L RIB + ET vs combo CT in pre- or perimenopausal Asian and non-Asian pts with HR+/HER2− ABC. NR, not reached. a Unconfirmed; b Docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine.
Sub- group Arm n mPFS (95% CI), mo HR (95% CI) mTTF (95% CI), mo HR (95% CI) 3-mo TFR (95% CI), % ORR, %a CBR, %a mTTR (95% CI), moa 60 25.2 (17.1-NR) 0.43 (0.25-0.74) 19.5 (12.7-NR) 0.42 (0.26-0.68) 10.0 (3.8-20.5) 71.7 81.7 4.6 (3.0-6.6) 58 10.2 (8.3-18.4) 8.5 (6.7-13.6) 19.0 (9.9-31.4) 56.9 74.1 4.7 (2.7-NR) 52 21.1 (10.2-NR) 0.75 (0.42-1.32) 18.6 (10.2-24.0) 0.48 (0.29-0.80) 13.5 (5.6-25.8) 57.7 78.8 7.4 (4.4-NR) 52 12.8 (8.8-18.4) 8.8 (6.6-12.3) 25.0 (14.0-38.9) 63.5 71.2 2.9 (1.4-4.5)
Clinical trial identification
NCT03839823. Release date is September 17, 2018.
Editorial acknowledgement
Editorial assistance in the writing of the abstract was provided by Shashank Tandon, PhD of MediTech Media.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
Y. Yap: Financial Interests, Personal, Other, Honoraria: Novartis, AstraZeneca, MSD, Inivata, Specialised Therapeutics, Roche, Pfizer, Lilly/DKSH, Eisai; Non-Financial Interests, Personal, Other, Travel Support: AstraZeneca, Lilly/DKSH; Financial Interests, Personal and Institutional, Research Grant: MSD. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Local PI, Clinical Trial Budget: AstraZeneca, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Coordinating PI, Clinical Trial Budget: Eisai; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. Y. Lu: Other, Personal and Institutional, Other, Clinical trial study fee: Novartis; Financial Interests, Institutional, Research Grant, Grant for clinical study for ESR1 mutation detected by cell free DNA: Novartis; Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Pfizer, Roche, Merck Sharp & Dohme, Pfizer, Eisai, AstraZeneca, Eli Lilly, Daiichi Sankyo; Financial Interests, Personal, Other, Contracted research: Roche, Merck Sharp & Dohme, Pfizer; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, Pfizer, AstraZeneca; Financial Interests, Personal and Institutional, Other, Clinical trial: AstraZeneca. H.A. Azim: Financial Interests, Personal, Advisory Board, honoraria for advisory boards and lecturing: Pfizer, MSD, BMS, ASZ, Lilly, Roche, Novartis; Non-Financial Interests, Personal and Institutional, Other, supporting educational activities for my academic institution: Novartis, Pfizer, MSD, BMS, ASZ; Financial Interests, Personal and Institutional, Other, supporting educational activities for my academic institution: Lilly. Y. Eralp: Financial Interests, Personal, Advisory Board: Novartis, Merck, Sharp and Dohme, AstraZeneca; Financial Interests, Personal, Other, Educational fee: Gilead, GSK; Financial Interests, Institutional, Research Funding, Research support: Roche; Non-Financial Interests, Personal, Other, Non-compansated educational program: Roche, Novartis; Financial Interests, Personal, Advisory Board, Non-compansated mentorship program: Boston Scientific; Financial Interests, Personal, Other, Satellite meeting fee: Roche. A. Thuerigen: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. T. Delgar Alfaro: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. J. Wu: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. M. Gao: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. N.S. El Saghir: Financial Interests, Personal, Invited Speaker, Speaker conference: AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker, Conference: Lilly, Pfizer; Financial Interests, Personal, Invited Speaker, Speaker and/or adboard: MSD; Financial Interests, Personal, Invited Speaker, Speaker meeting: Pierre Fabre; Financial Interests, Institutional, Coordinating PI, Clinical Trial co-PI: Novartis. All other authors have declared no conflicts of interest.
Invited Discussant LBA3, LBA6 and 57MO
- Mastura Md Yusof (Kuala Lumpur, MY)
- Mastura Md Yusof (Kuala Lumpur, MY)
Q&A and discussion
- All Speakers (Lugano, CH)
- All Speakers (Lugano, CH)