•101 patients with HER2+ MBC on pertuzumab and trastuzumab were included.•Most observed cardiotoxicity were mild, all occurred early within 24 months.•Presence of cardiovascular co-morbidities ...predicts treatment cardiotoxicity.•Risk-stratified de-escalation of long-term cardiac surveillance should be discussed.
e13069 Background: In patients with hormone receptor-positive, HER2-negative metastatic breast cancer (HR+ HER2- MBC), the correlation between the level of expression of HR and the clinical efficacy ...of CDK4/6 inhibitors remains undefined. Methods: We identified consecutive patients with HR+ HER2- MBC starting a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) plus either an aromatase inhibitor or fulvestrant between Jan 2018 - Oct 2023 from an institutional cancer registry. Expression level of HR was stratified as high (H) (Allred score 7-8), moderate (M) (Allred score 5-6) or low (L) (Allred score 3-4) for both estrogen (ER) and progesterone receptors (PR). Patients were evaluated from start of treatment to December 2023, last visit or death, whichever came earlier. Median progression-free survival (mPFS) and overall survival (mOS) were endpoints. We evaluated the association of HR expression levels with mPFS and mOS using log-rank test and multivariate Cox regression modelling. Results: We examined data from 436 women with HR+ HER2- MBC. Median age at treatment was 60.5 yr. Majority of patients received the treatment in the first-line setting (72.5%), with palbociclib (54.1%), ribociclib (31.9%) and abemaciclib (14.0%) as the CDK4/6 inhibitor. In the population that received first-line treatment, ER expression levels were H (83.5%), M (11.4%) and L (5.1%) respectively. ER expression levels were strongly associated with mPFS and mOS. For ER H, M and L expressions, mPFS were 29.4m, 9.2m and 2.9m ( p<0.001); mOS were 52.1m, 40.6m and 11.6m ( p<0.001), respectively. In multivariate analysis, ER expression levels remain strongly predictive for both mPFS and mOS after adjustment for clinicopathological risk factors (ER L vs H, mPFS HR 10.6, p<0.001; mOS HR 4.66, p<0.001; ER M vs H, mPFS HR 4.90, p<0.001; mOS HR 2.06, p=0.05). Findings were similar for the second line and beyond population. In the ER-high expression cohort, the PR expression levels also correlate strongly with treatment efficacy and survival, with mPFS of 40.8m, 24.5m, 24.0m, 14.1m ( p<0.001) and mOS of NR, 53.3m, 48.1m, 26.9m ( p<0.001) respectively for PR H, M, L and zero expressions. Conclusions: In this real-world cohort of patients with HR+ HER2- MBC, we observed that the semi-quantitative HR expression level subgrouping is a strong predictor for the efficacy of treatment with CDK4/6 inhibitors. In contrast to patients with high HR expression levels, the small population with ER-low expression derived very limited benefits from the standard endocrine therapy with CDK4/6 inhibitors. Our findings provided a practical tool to guide the selection of the appropriate systemic therapy for individual patients.
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Background: Dual anti-HER2 antibodies pertuzumab (P) and trastuzumab (T) in combination with taxane (D), followed by PT maintenance, is the standard first line treatment for HER2 positive ...advanced breast cancer (HER2+ ABC). Treatment associated cardiotoxicity necessitates regular cardiac function surveillance, which is a burden particularly for treatment long-responders. Data for cardiac safety of prolonged P+T exposure is scarce. We investigate the real-world impact on cardiac function in long-responders to treatment with dual anti-HER2 antibodies. Methods: We identified consecutive patients with HER2+ ABC who received the CLEOPATRA regimen (PT-D) between Jan 2014 and Dec 2020 from an institutional cancer registry. All patients had pre-treatment multiple-gated acquisition (MUGA) scan or echocardiogram, and subsequently at 3-monthly intervals until end of treatment to monitor left ventricular ejection fraction (LVEF). Patients on treatment for ≥36 months were considered long-responders. The Wilcoxon signed-rank test was used to assess any significant difference in LVEF at various landmark time-points in comparison to their pretreatment baseline. Results: 101 women with HER2+ ABC were eligible for analysis. Median age at treatment was 62 (IQR, 56.0-69.0). The median duration of treatment was 17.3 months (IQR, 9.0-31.3). 22.8% of patients were long-responders, who received a median of 67 cycles of treatment (IQR, 58-88). Compared to baseline, median LVEF was significantly decreased at 6m (median, 66% vs 69%, p=0.02), however there were no significant differences for any of the subsequent time-points up to 84 m. All of the larger LVEF drop (≥10% from baseline) occurred by the first 24 months, representing 4.7% of the overall measurements. Risk factors present for patients experienced treatment suspension (n=3) included previous exposures to anthracycline and left sided radiotherapy. Conclusions: In patients with HER2+ ABC who were long-responders to first-line PT-D, prolonged exposure to dual anti-HER2 antibodies was not associated with significant cardiotoxicity. It is safe to de-escalate the cardiac surveillance for this population. Table: see text
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Background: Achieving pCR following neoadjuvant chemo and anti-HER2 therapy is associated with a significantly better survival in HER2+ BC. There is currently a lack of a robust biomarker to ...predict pCR in HER2+ BC. Using EFTUD2 as chromosome 17 reference probe, circulating HER2/EFTUD2 plasma DNA copy number ratio (H-ratio) detected by droplet digital PCR (ddPCR) was shown to have high concordance with the tumor HER2 status. We aim to evaluate whether the change in H-ratio is associated with response to neoadjuvant dual anti-HER2 therapy. Methods: We prospectively recruited patients with HER2+ BC who received neoadjuvant taxane, trastuzumab and pertuzumab followed by radical surgery from May 2019 to April 2022. Serial plasma samples (n = 49) were collected at pre-treatment (Tpre), at 4th cycle (Tmid) and at completion of neoadjuvant treatment (Tpost). H-ratio was determined in each plasma sample using droplet ddPCR (QX200 ddPCR system, Bio-rad). H-ratio responders were defined as patients having a declining Tpost H-ratio, whereas patients having a rising or persistent Tpost H-ratio were defined as H-ratio non-responders. The relationship between pCR, H-ratio and various clinicopathological characteristics were evaluated by Spearman’s correlation, Fisher’s exact test and Wilcoxon signed-rank test. Results: Eighteen clinical stage II or III HER2+ BC patients with a median age of 56 years old (range 33 - 71) were included. The median H-ratio at Tpre, Tmid and Tpost were 1.27, 1.12 and 1.10, respectively. Higher Tpre H-ratio was significantly associated with larger tumor size (p = 0.004) and higher tumor grade (G1-2 vs G3; median H-ratio 1.15 vs 1.78; p = 0.024). Six patients (33.3%) were H-ratio responders. Ten (55.6%) of 18 patients achieved pCR after completion of neoadjuvant treatment. The pCR rate in H-ratio responders was significantly higher than the H-ratio non-responders (100% vs. 36.4%; p = 0.017). In predicting pCR, H-ratio response outperformed hormonal receptor (HR) negativity (HR- vs HR+; 72.7% vs 28.6%; p = 0.088) or high tumor grade (G1-2 vs G3; 66.7% vs 33.3%; p = 0.201). There was no association between pCR and Tpre/Tmid/Tpost H-ratio. With a median follow up of 22.8 months (range 8.2 - 41.8), there were no relapse or death. Conclusions: A high pre-treatment plasma circulating HER2/EFTUD2 ratio is associated with large tumor size and high tumor grade in HER2+ BC. The decline of HER2/EFTUD2 ratio after neoadjuvant dual anti-HER2 therapy predicts pCR, and may serve as a potential biomarker for treatment de-escalation.
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Background: Gastric cancer is the fourth leading cause of cancer death worldwide. Lack of symptoms in the early stage of disease leads to delayed presentation and low overall survival rate. ...Early detection is key, but there is not yet an established test for non-invasive gastric cancer screening. Routine blood test panels, including complete blood count, liver function, renal function and clotting profiles, could be potentially useful in reflecting bodily processes related to cancer. Current literature and territory-wide statistical data analyses from Hong Kong have shown these subtle changes and differences in measured levels of subcomponents between individuals with and without gastric cancer, that are not recognized clinically, form recognizable patterns distinct to gastric cancer. In this study, we hypothesized that gastric cancer signatures could be identified in routine blood data. Deep learning AI algorithms are used to identify the gastric cancer signature. Results from testing and validation of the identified routine blood signature using a Big Clinical Data cohort are reported. Methods: This is a territory-wide healthcare database study using data from Hong Kong Hospital Authority data collaboration laboratory. All patients prescribed with medications for dyspepsia and with all blood tests components (CBC, LFT, RFT, clotting function) available in the period between 2004-2015 inclusive were included. In the period, data from 2004 to 09 and 2011 to 14 were used as training cohort and the rest were used as testing cohort. A blood gastric cancer signature was generated using deep learning AI algorithms, and applied to predict gastric cancer in Big Data population. Results: 193,117 patients were included in the captioned period, in whom 4,790 patients were diagnosed to have gastric cancer. 151,449 (3,815 pts with gastric cancer and 147,634 pts disease free) patients were included In training cohort. In the testing cohort in 2010 and 2015 (975 pts with gastric cancer and 40,693 pts disease-free), the tumor signature yielded a sensitivity of 0.79, specificity of 0.99, positive predictive value of 0.95 and a negative predictive value of 0.99. Conclusions: The hypothesis of the presence of a distinctive gastric cancer signature from parameters in routine blood test data is tested and validated in a large population cohort with dyspepsia. The signature has high accuracy and high sensitivity with low false positive and false negative rates. Multicenter prospective testing is being conducted in cohort indicated for OGD in Hong Kong.Table: see text
We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other ...biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients.
We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters.
We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of interalpha-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4.
Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.
Background & Aims:
Hepatitis B virus reactivation is a serious cause of morbidity and mortality in hepatitis B surface antigen-positive patients treated with chemotherapy. We compared the efficacy of ...early and deferred preemptive lamivudine therapy in reducing the incidence of hepatitis due to hepatitis B virus reactivation in hepatitis B surface antigen-positive lymphoma patients treated with chemotherapy.
Methods:
Thirty consecutive hepatitis B surface antigen-positive lymphoma patients undergoing intensive chemotherapy were randomized (1:1) to receive lamivudine 100 mg daily 1 week before chemotherapy (group 1) or to have this treatment deferred until there was serological evidence of hepatitis B virus reactivation on the basis of serial 2-week-interval serum hepatitis B virus DNA monitoring by a Digene Hybrid Capture II assay (group 2).
Results:
Eight (53%) patients in group 2 and none in group 1 had hepatitis B virus virological reactivation after chemotherapy (
P = 0.002). Seven patients in group 2 still had hepatitis (5 anicteric hepatitis, 1 icteric hepatitis, and 1 hepatic failure). Survival free from hepatitis due to hepatitis B virus reactivation in group 1 patients was significantly longer than that in group 2 (
P = 0.002 on the log-rank test). The median onset of hepatitis B virus reactivation in these patients was 16 weeks (range, 4–36 weeks) after the initiation of chemotherapy. Three (13%) of the 23 patients treated with lamivudine had hepatitis B virus-related hepatitis after lamivudine withdrawal.
Conclusions:
Lamivudine should be considered preemptively before or at the initiation of chemotherapy for all hepatitis B surface antigen-positive lymphoma patients undergoing intense chemotherapy.
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