Anemia is the most common hematological abnormality in cancer patients, unfortunately, it is often under-recognized and under-treated. The pathogenesis of cancer anemia is complex and most of the time multifactorial; involving factors related to the tumor itself or its therapy. While anemia can present in a wide range of symptoms, involving almost every organ, it is believed that it contributes much to cancer-related fatigue, one of the most common symptoms in cancer patients. In addition, there is increasing evidence to suggest that anemia is an independent factor adversely affecting tumor response and patient survival. While blood transfusion was the only option to treat cancer-related anemia, the use of recombinant human erythropoietin (rHuEPO) is becoming the new standard of care, more so with the recent studies demonstrating the feasibility of a single weekly injection. Things are even getting better with the recent approval of a new form of rHuEPO; Darbepoetin, an analogue with a 3-fold longer half-life. In addition to its effect in raising hemoglobin, several well-controlled studies demonstrated decrease in transfusion requirements and better quality of life assessed objectively using standard assessments scales.
Breast cancer is the most commonly diagnosed cancer in women worldwide. Over the past decade, the treatment paradigm for patients with metastatic breast cancer (MBC) has taken an important shift towards better survival and improved quality of life (QOL), especially for those with hormone receptor (HR)-positive diseases which represent the majority of breast cancer subtypes. The introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in the upfront therapy of such patients has resulted in dramatic improvement in progression-free survival (PFS) and overall survival (OS), too. However, almost all patients would, sooner or later, develop disease progression and necessitate transition to different lines of treatment that may include chemotherapy. The idea of maintaining CDK4/6 inhibitors beyond disease progression seems attractive, as this approach has the potential to improve outcome in this setting despite the fact that the true benefit, in terms of survival, might not carry the same weight as it initially does. Researchers have been investigating potential mechanisms of resistance and identify possible biological markers for response after disease progression. Much of the available data is retrospective; however, few randomized clinical trials were recently published and few more are ongoing, addressing this point. In this paper, we intend to review the available published studies investigating the potential role for keeping CDK4/6 inhibitors in play beyond disease progression.
e11579 Background: BOLERO-2 phase III trial clearly demonstrated the efficacy of everolimus (EVE) plus exemestane (EXE) for the treatment of postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer (aBC). However, in this study only a minority ( < 10%) of patients were recruited from African and Asia Pacific countries (except Japan). Considering the potential effects of ethnic and cultural differences on treatment effectiveness, it remains compelling to confirm the safety and efficacy profile of EVE+EXE in these populations. Methods: EVEREXES is an open-label phase IIIb, single arm, multi-center trial, which enrolled 251 post-menopausal, HR-positive and HER2-negative, aBC patients who were treated with EVE+EXE across 13 Asia Pacific and African countries. Its primary objective was to investigate the safety and tolerability profile of EVE+EXE. Secondary objectives were the evaluation of efficacy (assessed by PFS, ORR, and CBR based on RECIST 1.1 criteria) and change in ECOG performance status. Results: From March 2013 to October 2014, 251 patients were enrolled across Asia Pacific, Middle East, North and South Africa. At data cut off of 30st of November 2014, a majority of grade 1/2 adverse events (AEs) was reported, with a small proportion ( < 10%) of ≥ grade (G) 3 AEs. In particular, 66% of patients developed stomatitis (9% G3), 53% skin toxicity (2% G3), 32% infections (4% ≥ G3), 26% hyperlipidemia (2% G3), 17% elevated liver enzymes (6% G3), 14% hyperglycemia (5% G3) and 10% noninfectious pneumonitis (with just 1 case ≥ G3). Overall, 47% of patients underwent dose adjustments/temporary interruptions and 7% permanently discontinued treatment due to AEs. Conclusions: These results are in line with those previously reported in BOLERO-2 trial, with EVE+EXE safety profile being predictable and manageable. Efficacy and safety data of EVE+EXE at January 31, 2015 data cut off will be presented for the first time in the above mentioned patient population with a median follow up of approximately 11 months, fostering further evaluation of the impact of ethnic and cultural differences on treatment outcomes.
Abstract Genetic counseling and testing are more accessible than ever due to reduced costs, expanding indications and public awareness. Nonetheless, many patients missed the opportunity of genetic counseling and testing due to barriers that existed at that time of their cancer diagnoses. Given the identified implications of pathogenic mutations on patients’ treatment and familial outcomes, an opportunity exists to utilize a ‘traceback’ approach to retrospectively examine their genetic makeup and provide consequent insights to their disease and treatment. In this study, we identified living patients diagnosed with breast cancer (BC) between July 2007 and January 2022 who would have been eligible for testing, but not tested. Overall, 422 patients met the eligibility criteria, 282 were reached and invited to participate, and germline testing was performed for 238, accounting for 84.4% of those invited. The median age (range) was 39.5 (24–64) years at BC diagnosis and 49 (31–75) years at the date of testing. Genetic testing revealed that 25 (10.5%) patients had pathogenic/likely pathogenic (P/LP) variants; mostly in BRCA2 and BRCA1 . We concluded that long overdue genetic referral through a traceback approach is feasible and effective to diagnose P/LP variants in patients with history of BC who had missed the opportunity of genetic testing, with potential clinical implications for patients and their relatives.
Triple-negative breast cancer (TNBC) patients exhibiting pathological complete response (pCR) have better clinical outcomes compared to those with residual disease (RD). Therefore, robust biomarkers that can predict pCR may help with triage and resource prioritization in patients with TNBC. Herein, we identified a gene panel predictive of RD and pCR in TNBC from the discovery (n = 90) treatment-naive tumor transcriptomic data. Eight RD-derived genes were identified as TNBC-essential genes, which were highly predicative of overall survival (OS) and relapse-free survival (RFS) in an additional cohort of basal breast cancer (n = 442). Mechanistically, targeted depletion of the eight genes reduced the proliferation potential of TNBC cell models, while most remarkable effects were for combined SLC39A7, TIMM13, BANF1, and MVD knockdown in conjunction with doxorubicin. Orthogonal partial least squares-discriminant analysis (OPLS-DA) and receiver operating characteristic curve (ROC) analyses revealed significant predictive power for the identified gene panels with an area under the curve (AUC) of 0.75 for the validation cohort (n = 50) to discriminate RD from pCR. Protein-Protein Interaction (PPI) network analysis of the pCR-derived gene signature identified an 87-immune gene signature highly predictive of pCR, which correlated with better OS, RFS, and distant-metastasis-free survival (DMFS) in an independent cohort of basal and, to a lesser extent, HER2+ breast cancer. Our data have identified gene signatures predicative of RD and pCR in TNBC with potential clinical implications.
Cancer is the second leading cause of death in Jordan after cardiovascular diseases. Due to increase in life expectancy and prolonged exposure to risk factors, cancer mortality and morbidity are expected to increase as the young population ages. This increase will constitute a challenging burden on healthcare systems in Jordan and many other neighboring countries. Planning is key to managing the expected rise in the demand for cancer care, and this will require public health initiatives to guarantee access to quality cancer care. Over the past decade, cancer care in Jordan has witnessed remarkable improvement through access to advanced diagnostics and therapeutics. In this review, we address the history of cancer care in Jordan, including cancer statistics, infrastructure, workforce as well as cancer care outcomes. We also discuss many of the challenges that we face and offer suggestions for the improvement of cancer management in Jordan and the region.
Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer Hikmat Abdel-RazeqDepartment of Internal Medicine, King Hussein Cancer Center, Amman, JordanI read with great interest the review written elegantly by Gradishar addressing the challenges that community oncologists face in treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative advanced breast cancer in your journal.1As the author correctly stated, resistance to endocrine therapy in women with hormone receptor-positive disease is very frequent and almost inevitable.Understanding the multiple known mechanisms for endocrine resistance has helped physicians and researchers target these pathways.2 Many of the recently introduced drugs, such as the mTOR inhibitor everolimus3 and the cyclin-dependent kinase (CDK 4/6) inhibitor palbociclib,4 are in clinical practice and have been already incorporated in international guidelines.5View original paper by Gradishar.
Venous thromboembolic events (VTE) are commonly encountered in patients with lymphoma. Several risk assessments models (RAM) had attempted to identify higher risk patients with varying success. The International Prognostic Index (IPI) is a clinicopathological tool developed to help predict both response to treatment and prognosis of patients with diffuse large B-cell lymphoma (DLBCL).In this study, we utilize the IPI index to identify group of patients with DLBCL at higher risk for VTE.Patients with pathologically-confirmed diagnosis of DLBCL and with image-confirmed VTE, treated and followed at our institution were included. Rates of VTE was calculated for each risk category.A total of 373 patients, median age 49 (range: 18-90) years were included. VTE were reported in 56 (15.0%) patients; 51 (91.1%) had active disease while 29 (51.8%) were ambulatory at time of VTE diagnosis. VTE rates were particularly high among patients with poor performance status (26.2%, P=0.028) and high LDH (19.0%, P=0.023). Applying the age-adjusted IPI separated patients into two risk categories; VTE were diagnosed in 9.7% in patients with "low and low-intermediate" scores compared to 19.8% in patients with "high and high-intermediate" scores, P=0.020.The original IPI and its modified versions, routinely used at diagnosis as a prognostic and predictive tool for patients with DLBCL, can also be utilized to define high risk patients for VTE; the risk of whom might be high enough to recommend thromboprophylaxis even in the ambulatory settings. More work is needed to refine and improve currently available RAMs.
Metaplastic breast cancer (MetBC) represents a therapeutic challenge. We evaluated the impact of clinicopathological characteristics and treatment modalities on outcomes among MetBC patients treated at our center.Women with stage I-III MetBC were reviewed from our database from 2005-2018. Kaplan-Meier method was used to calculate locoregional-failure-free survival (LRFFS), overall-survival (OS) and distant-metastases-free survival (DMFS). We assessed associations with survival outcomes by log-rank tests. Multivariate Cox proportional-hazards models were used to identify independent predictors of LRFFS, OS and DMFS.81 patients were eligible for the study. Median age at diagnosis was 48 years. 90.1% had G-III tumors, 64.2% were pathologically node negative and lympho-vascular invasion (LVI) was absent in 72.8%. 67.8% were triple negative, and 7.4% were HER2-neu positive. Most (66.7%) patients underwent mastectomy. Free margins were achieved in the entire cohort, however, 17.3% had close margin (<2 mm). Almost all patients received chemotherapy. 75.3% received radiotherapy, 23.5% received hormonal therapy and 6.2% received Trastuzumab. With a median follow-up of 54 months, 18.5% developed loco-regional recurrence and 34.6% relapsed distally. Five-year OS was 66.0%. On multivariate analysis: adjuvant radiotherapy correlated with better OS (P < .0001), and tumor size >5 cm, nodal involvement and LVI correlated with worse OS, (P = .019, P = .021, P = .028, respectively). There were no survival differences with respect to age, triple negativity, and morphologic subtype.We report the largest single institutional series on MetBC in the Middle East region. MetBC confers worse survival outcomes, and more aggressive local and systemic treatment strategies should be investigated.
Cyclin dependent kinase (CDK) 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) modulate endocrine resistance and are integral treatment for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Since their approval, CDK4/6 inhibitors are widely used in clinical practice. Thromboembolic events (TEE) were not a major issue in patients treated on clinical trials utilizing these agents. However, conflicting data started to emerge describing higher than expected rates of both arterial and venous thrombosis in patients treated with CDK4/6 inhibitors. In this study, we report our experience on TEE in patients treated with one of these agents (ribociclib) in real-world settings.All consecutive patients with metastatic breast cancer (mBC) treated with ribociclib combined with letrozole or fulvestrant were retrospectively reviewed. All episodes of radiologically confirmed arterial or venous thrombosis were recorded. TEE was considered ribociclib-related if diagnosed while patients are on the drug, or within 4 weeks after the last dose.A total of 305 patients, median age (range), 49 (22-87) years were enrolled. All patients had metastatic disease, and most (n=241, 79.0%) were with visceral metastasis. Ribociclib was used for a median duration of 7 months (range: 1-45) and was used beyond the first-line setting in 110 (35.9%) patients. TEE were confirmed on 6 (1.97%) patients; 3 were pulmonary embolism, 2 cerebral venous sinus thrombosis (CVST), and one case of limb ischemia and all were symptomatic. Similar rates of TEE were noted prior to initiation, and after stopping ribociclib.In real-world settings, breast cancer patients treated with ribociclib, combined with aromatase inhibitors or fulvestrant, may not be at higher risk for thromboembolic events. However, unusual sites of thrombosis, like CVST, may raise some concerns.
