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Osimertinib is the current first-line treatment for EGFR-mutated NSCLC, however, patients frequently relapse due to acquired resistance mutations. Amivantamab is a bispecific antibody against EGFR and MET alterations. Lazertinib is a tyrosine kinase inhibitor active against EGFR mutations including common resistance mutations. The MARIPOSA trial was designed to study if the combination of amivantamab plus lazertinib in untreated epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients would provide improved progression-free survival. Here, we discuss the rationale for the study and the early results of MARIPOSA.

Pulmonary mucoepidermoid carcinoma (PMEC) is a rare tumor with limited clinical data available due to its low incidence. So far, there are no universal treatment guidelines for this malignant tumor. We present here the case of a 59-year-old female never smoker who was initially referred to our hospital with cough and hemoptysis and was eventually diagnosed with PMEC. Based on further genetic testing, echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase (EML4-ALK) fusion variants E20:A20 (V2) was found. The patient was treated with lorlatinib as the first-line treatment. This case is the first to describe the effectiveness of lorlatinib in treating an advanced high-grade PMEC with EML4-ALK fusion V2 mutation patient. [ABSTRACT FROM AUTHOR]

Abstract Programmed Death Receptor 1 (PD-1) inhibitors, when combined with chemotherapy, have exhibited notable effectiveness in enhancing the survival outcomes of patients afflicted with advanced gastric cancer. However, it is important to acknowledge that not all patients derive substantial benefits from this therapeutic approach, highlighting the crucial necessity of identifying efficacious biomarkers to inform immunotherapy interventions. In this study, we sought to investigate the predictive utility of circulating tumor DNA (ctDNA) as a biomarker in a cohort of 30 patients diagnosed with advanced gastric cancer, all of whom underwent first-line treatment involving PD-1 inhibitor administration alongside chemotherapy. We procured peripheral blood samples both at baseline and following the completion of two treatment cycles. Additionally, baseline tissue specimens were collected for the purpose of genomic alteration assessment, employing both 47-gene and 737-gene next-generation sequencing panels for plasma and tumor tissue, respectively. We delineated a ctDNA response as the eradication of maximum variant allele frequencies relative to baseline levels. Notably, the objective response rate among individuals exhibiting a ctDNA response proved significantly superior in comparison to non-responders (P = 0.0073). Furthermore, patients who manifested a ctDNA response experienced markedly prolonged progression-free survival (PFS) and overall survival (OS) when juxtaposed with those devoid of a ctDNA response (median PFS: 15.6 vs. 6.0 months, P = 0.003; median OS: not reached [NR] vs. 9.0 months, P = 0.011). In summation, patients with advanced gastric cancer receiving first-line treatment with PD-1 inhibitors and chemotherapy, dynamic changes in ctDNA can serve as a potential biomarker for predicting treatment efficacy and long-term outcomes.

Danielle Brazel,1 Misako Nagasaka2,3 1Department of Hematology/Oncology, Scripps Clinic/Scripps Green Hospital, La Jolla, CA, USA; 2Department of Hematology/Oncology, University of California Irvine School of Medicine, Chao Family Cancer Center, Orange, CA, USA; 3Department of Medicine, St. Marianna University School of Medicine, Kawasaki, JapanCorrespondence: Misako Nagasaka, University of California Irvine School of Medicine Chao Family Cancer Center, 101 The City Drive, Orange, CA, 92868, USA, Email nagasakm@hs.uci.eduAbstract: Osimertinib is the current first-line treatment for EGFR-mutated NSCLC, however, patients frequently relapse due to acquired resistance mutations. Amivantamab is a bispecific antibody against EGFR and MET alterations. Lazertinib is a tyrosine kinase inhibitor active against EGFR mutations including common resistance mutations. The MARIPOSA trial was designed to study if the combination of amivantamab plus lazertinib in untreated epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients would provide improved progression-free survival. Here, we discuss the rationale for the study and the early results of MARIPOSA.Keywords: epidermal growth factor receptor (EGFR) mutations, first line treatment, bispecific antibody

The COVID-19 pandemic posed a major challenge in cancer care worldwide which might have an impact on the management of diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective study comparing characteristics, management, and outcomes of DLBCL patients diagnosed during the first year of the COVID-19 pandemic (1/3/2020–28/2/2021) to those diagnosed in the previous year (1/3/2019–28/2/2020) in two tertiary centers in Italy and Israel. 182 patients were diagnosed with DLBCL during the study period. More patients were diagnosed during the pandemic compared to the year before: 60 vs. 29 and 54 vs. 39 in Italy and in Israel, respectively. Trends towards older age and higher transformation rates were shown during the pandemic. The interval between the initiation of symptoms and diagnosis was longer during the pandemic. Five and four patients were diagnosed with COVID-19 during treatment in Italy and in Israel, respectively. there was no difference in dose density and intensity of treatment, before and during the pandemic. The median follow-up during and before the pandemic was 15.2 and 25.5 months, respectively. Progression-free survival (PFS) was slightly shorter during the pandemic compared to the year before (64.9% vs. 70.6%; p = 0.0499). In multivariate analysis, older age and transformed disease were independently related to PFS, while diagnosis of DLBCL during the pandemic was not. Despite the challenges caused by COVID-19 pandemic, the management of DLBCL patients remained unchanged including dose density and intensity. Nevertheless, a shorter PFS during the outbreak might be attributed to differences in patients' characteristics. [ABSTRACT FROM AUTHOR]

BackgroundWaldenström macroglobulinemia (WM) is a rare and indolent B-cell lymphoproliferative disorder with greater incidence in elderly patients where a precise algorithm of initial therapy is still not clear. Immunochemotherapy regimen consisting of dexamethasone, rituximab, and oral cyclophosphamide (DRC) is considered a suitable first-line treatment because of its safety, efficacy, and manageability.Patients and methodsWe retrospectively describe the results of 36 consecutive treatment-naïve patients with WM who were treated from June 2013 until June 2021 with the DRC regimen every 4 weeks instead of 3 weeks, for six cycles. The median age was 69 years (range, 42–85 years), with one-third being older than 75 years. Most patients had features of advanced disease, with nearly 60% being high risk. Median IgM level prior to treatment initiation was 2.9 g/dL.ResultsOverall response rate was 80% after a median time of two cycles, with 67% of patients achieving at least partial response. After a median follow-up of 59 months, the median overall survival (OS) was not reached and the median time to next treatment (TTNT) was 48 months (95% CI 25–87 months). Approximately 70% of the evaluable study population had a 3-year survival without additional treatment, while 75% had a 3-year OS rate. The treatment was well-tolerated with only two patients (6%) recorded to have grade 3 pneumonia and no grade 3 hematological toxicity maybe due to the regular use of growth factors for red and white blood cells. Baseline albumin level and achievement of at least minimal or partial response had a significant impact on TTNT, while baseline hemoglobin and IgA level affected outcome in terms of OS (p < 0.05).ConclusionThis is the first real-life experience describing the use of the DRC regimen in treatment-naive patients with WM with administration of therapy every 4 weeks instead of 3 weeks showing apparent comparable efficacy, along with good tolerability and safety, especially in terms of hematological toxicity, independently from comorbidity burden.

Background: Immunotherapy represents a new form of treatment that stimulates the immune system to destroy cancer cells. Pembrolizumab is a humanized monoclonal antibody that binds to the PD-1 programmed cell death receptor and blocks its interaction with the PD-L1 and PD-L2 ligands. The aim of this study was to determine the efficacy and safety of the pembrolizumab drug, in the first line of treatment in patients with metastatic non-small cell lung cancer (NSCLC). Methods: The research was retrospective and was conducted at the Institute for Pulmonary Diseases of Vojvodina (IPDV). It included patients treated in the period from January 2018 to December 2019, in whom metastatic NSCLC was verified. Results: The study included a total of 20 patients - 10 men and 10 women. The average age was 61.75 years. The average length of therapy was 15 cycles (45 weeks), the minimum was 1, and the maximum was 33. Twelve patients (60%) had a lethal outcome. The median time to disease progression was 8.1 months and the overall survival was 14.6 months. Of the total number of patients, 13 (65%) had side effects to immunotherapy, and 7 (35%) did not experience any. Out of a total of 13 patients who had side effects, 9 had only one isolated, 4 had more associated side effects, of which 3 patients had 2 associated, and 1 patient had 3 associated side effects. Conclusion: Based on the results, immunotherapy certainly occupies an important place in the treatment of metastatic NSCLC. Namely, the lack of severe side effects linked to cytotoxic chemotherapy and the relative ease of treating immune related adverse events (irAEs) that occur with immunotherapy, good overall survival and later onset of disease progression opens the door to the possibility of a better quality of life for these patients and the prolongation of their lifespan.

During the last 15 years, tremendous efforts have been made in the medical treatment of metastatic renal cell carcinoma (mRCC). Immune-oncological (IO) combinations are the current standard of care in the first-line setting of mRCC. Here, the current phase 3 trials CM214 (nivolumab/ipilimumab vs. sunitinib), KN426 (axitinib/pembrolizumab vs. sunitinib), Javelin-ren-101 (axitinib/avelumab vs. sunitinib), CM9ER (cabozantinib/nivolumab vs. sunitinib), and CLEAR (lenvatinib/pembrolizumab vs. sunitinib) were discussed. In the mentioned phase 3 trials, primary and secondary endpoints were discussed. Strengths and weaknesses of each trial were reflected in terms of overall survival, progression-free survival, objective remission, health quality of life, and safety. Reflecting on the data, as well as the current ESMO guidelines, we discuss choosing the appropriate medical treatment for patients' individualized treatment journey and relay the strength and weaknesses of each combination—starting with the appropriate first-line therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute Myeloid Leukemia is the most common aggressive blood cancer in adults. Treatment for this condition is divided into induction followed by consolidation. The mainstay of treatment is chemotherapy, and until a decade ago, only traditional chemotherapy was approved for this condition. Induction involves treatment with intense chemotherapy for a span of 7 days. Once blood counts recover, patients undergo bone marrow biopsy to ensure remission status for the disease. Elderly patients who were considered too weak to receive intense therapy were treated with single-agent low-intensity therapy until the approval of a few new combinations starting in 2018. As a result, over the last 10 years, 10 new medications have been approved for the treatment of this type of leukemia. We discuss the evidence behind these treatment regimens and combinations. The word Leukemia was coined nearly 200 years ago by Rudolf Virchow. Once a death sentence, Acute Myeloid Leukemia (AML) is now a treatable condition. The introduction of "7 + 3" chemotherapy, originally reported from the Roswell Park Memorial institute in Buffalo, New York, in 1973, changed the treatment paradigm for AML. About twenty-seven years later, FDA approved the first targeted agent, gemtuzumab, to be added to this backbone. During the last seven years, we have had ten new drugs approved for the management of patients with AML. Work by many dedicated scientists led to AML achieving the elite status of being the first cancer to have the whole genome sequenced using next-generation sequencing. In the year 2022, we witnessed the introduction of new classification systems for AML by the international consensus classification and the world health organization, both emphasizing molecular classification of the disease. In addition, the introduction of agents such as venetoclax and targeted therapies have changed the treatment paradigm in older patients ineligible for intensive therapy. In this review, we cover the rationale and evidence behind these regimens and provide insights into the newer agents. [ABSTRACT FROM AUTHOR]

This study shows that delaying first-line medical treatment may safely undergo in patients with favorable IMDC group metastatic renal cell carcinoma without significantly compromising cancer control. For this population of patients under surveillance median systemic treatment-free survival was 39 months. Introduction and Objectives: Many patients in the favorable International Metastatic renal cell carcinoma (RCC) Data Base Consortium group (F-MRC) may have a relatively indolent disease course. Surveillance and delay of systemic therapy could be an option in this specific population. However, the question whether this delay could alter patients' outcome remains unanswered. Our objective was to determine if delaying first-line treatment influences the survival of F-MRC patients. Materials and Methods: We performed a retrospective multicenter national study involving the French Network for Research on Kidney Cancer UroCCR (NCT03293563). We included treatment naive F-MRC patients. We compared the overall survival of patients with immediate medical treatment (IMT) (started less than 3 months after metastatic diagnosis) to those with delayed medical treatment (DMT). Results: We included 90 patients treated between 2009 and 2018. The median time before occurrence of metastases from diagnosis was 28 (12-137) months. The two groups (IMT vs. DMT) were comparable for follow-up, age, sarcomatoid feature, number, and localization of metastatic sites and ECOG performance status. IMT was given in 25 (27.8 %) patients. Local treatment of metastasis (LTM) was performed in 47 (52%) patients. Patients with DMT had more LTM (63% vs. 24%, P = .001). Among patients with DMT (n = 65); 27 (41%) received a systemic treatment and median systemic treatment-free survival was 39 months (95% CI, 26.3-51.6). Median overall survival from metastasis disease diagnosis was 55 months (95% CI, 42.4-67.5) in the IMT group and 88 months (95%CI, 64-111.9) in the DMT group (P = .028). In multivariable analysis LTM was the only prognostic factor associated to survival improvement (HR: 0.33; P = .024). Conclusions: Selected Patients with FMRC may safely undergo DMT. LTM positively impacted survival in this population and should be considered whenever possible. Prospective trial with a larger population is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to analyse the characteristics of typical absence seizures (AS), myoclonic AS and AS with eyelid myoclonia in children and to find associations between these characteristics and difficult to treat absence seizures (DTAS). Methods: This was a single-center retrospective study. Electronic health records of pediatric patients with a clinical diagnosis of AS treated at a single tertiary epilepsy center between January 2013 and June 2020 were reviewed. Clinical characteristics, seizure information, ASM, and therapeutic response of patients were recorded. All patients were followed up for at least 1 year. DTAS were defined as failure to achieve remission after treatment with at least 2 anti-seizure medications (ASM), regardless of whether remission was achieved eventually in the study period. Results: Data from 131 patients were available for analysis. Remission was achieved after the first ASM treatment in 81 (61.8%) patients, and eventually in 120 (91.6%) during the study period. Epilepsy was classified as DTAS in 18 (13.7%) patients. AS weremore often difficult to treat in patients withmyoclonic AS and AS with eyelid myoclonia (40.0%), compared with patients with typical AS (11.4%; p=0.012, 95% CI 1.480-25.732). A positive family history of epilepsy (p = 0.046; 95% CI 1.021-8.572), a higher seizure frequency (p = 0.023, 95% CI 1.009-1.126) prior to ASM treatment, and longer time between seizure onset and treatment onset (p = 0.026; 95% CI 1.006-1.099) were also associated with DTAS. Significance: Our study suggests that several clinical characteristics of AS are associated with DTAS. One of these was the time between onset of AS and initiation of ASM treatment, which can be shortened with better care, suggesting that early diagnosis and treatment may improve prognosis in pediatric patients with AS. These findings remain to be confirmed in larger prospective studies. [ABSTRACT FROM AUTHOR]

Introduction: H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore.Methods: Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by 13C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI.Results: A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P < 0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674).Conclusion: First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar. [ABSTRACT FROM AUTHOR]

ObjectivesThe aim of this study was to analyse the characteristics of typical absence seizures (AS), myoclonic AS and AS with eyelid myoclonia in children and to find associations between these characteristics and difficult to treat absence seizures (DTAS).MethodsThis was a single-center retrospective study. Electronic health records of pediatric patients with a clinical diagnosis of AS treated at a single tertiary epilepsy center between January 2013 and June 2020 were reviewed. Clinical characteristics, seizure information, ASM, and therapeutic response of patients were recorded. All patients were followed up for at least 1 year. DTAS were defined as failure to achieve remission after treatment with at least 2 anti-seizure medications (ASM), regardless of whether remission was achieved eventually in the study period.ResultsData from 131 patients were available for analysis. Remission was achieved after the first ASM treatment in 81 (61.8%) patients, and eventually in 120 (91.6%) during the study period. Epilepsy was classified as DTAS in 18 (13.7%) patients. AS were more often difficult to treat in patients with myoclonic AS and AS with eyelid myoclonia (40.0%), compared with patients with typical AS (11.4%; p = 0.012, 95% CI 1.480–25.732). A positive family history of epilepsy (p = 0.046; 95% CI 1.021–8.572), a higher seizure frequency (p = 0.023, 95% CI 1.009–1.126) prior to ASM treatment, and longer time between seizure onset and treatment onset (p = 0.026; 95% CI 1.006–1.099) were also associated with DTAS.SignificanceOur study suggests that several clinical characteristics of AS are associated with DTAS. One of these was the time between onset of AS and initiation of ASM treatment, which can be shortened with better care, suggesting that early diagnosis and treatment may improve prognosis in pediatric patients with AS. These findings remain to be confirmed in larger prospective studies.

Abstract Background Although current therapy for patients with early-stage squamous cell carcinoma of the head and neck (SCCHN) is potentially curative, the recurrence rate is high. Patients with recurrent or metastatic (R/M) SCCHN have a poor prognosis and substantial disease burden, including impaired health-related quality of life (HRQoL), productivity loss and indirect costs, such as need for caregiver support. The aim of this study was to characterize the impact of R/M SCCHN and its first-line treatment on patient and caregiver quality of life, daily activities and work productivity using real-world evidence from Europe. Methods This was a multicentre retrospective study of patients with R/M SCCHN in France, Germany, Italy, Spain and the United Kingdom incorporating patient and caregiver surveys, and a physician-reported medical chart review, conducted between January and May 2019. Patients aged 18 or over with a physician confirmed diagnosis R/M SCCHN completed four validated measures of disease activity and its impact on quality of life and work productivity, while caregivers also completed questionnaire to assess the burden of providing care. Physicians provided data for clinical characteristics, patient management, testing history and treatment patterns. Results A total of 195 medical/clinical oncologists provided data for 937, predominantly male (72%) patients, with almost half of patients aged over 65 years. The most frequently reported symptoms were fatigue (43%), weight loss (40%), pain (35%) and difficulty swallowing (32%). The EXTREME regimen was the most common first line therapy in over half of patients, who reported moderate or extreme pain/discomfort, and anxiety/depression, and problems with self-care resulting in a diminished health status compared with the general population. Only 14% were employed with high absenteeism or presenteeism, and over half of patients had a caregiver for whom the burden of care was substantial. Conclusion Our results provide real-world insight into the multi-faceted burden associated with R/M SCCHN. The combination of poor HRQoL and the impairment in daily activities, social life and employment illustrates the wider impact of R/M SCCHN on patients and their caregivers, and highlights a need for novel 1 L treatment regimens to improve the humanistic and productivity burdens of this cancer.

Abstract Background L-asparaginase is a key component of treatment for patients with acute lymphoblastic leukaemia (ALL) in the UK. Commonly used forms of asparaginase are native E. coli-derived asparaginase (native asparaginase) and pegaspargase in first-line combination therapy, and native Erwinia chrysanthemi-derived asparaginase (Erwinia asparaginase) as second-line treatment. The objective of this study was to evaluate the cost-effectiveness of pegaspargase versus native asparaginase in first-line combination therapy for patients with newly diagnosed ALL. A combined decision tree and health-state transition Markov cost-effectiveness model was developed to assess the relative costs and health outcomes of pegaspargase versus native asparaginase in the UK setting. Results In base case analyses, first-line pegaspargase (followed by Erwinia asparaginase in cases of hypersensitivity) dominated first-line native asparaginase followed by Erwinia asparaginase; i.e. resulted in lower costs and more quality-adjusted life year gain. The favourable hypersensitivity rates and administration profile of pegaspargase led to lifetime cost savings of £4741 versus native asparaginase. Pegaspargase remained cost-effective versus all treatment strategies in all scenario analyses, including use of the 2500 IU/m2 dose, recommended for patients ≤21 years of age. Conclusions Pegaspargase, as part of multi-drug chemotherapy, is a cost-effective option for the treatment of newly diagnosed ALL. Based on this study, The National Institute for Health and Care Excellence Technology Appraisal Committee concluded that it could recommend pegaspargase as a cost-effective use of National Health Service resources in England & Wales for treating ALL in children, young people and adults with untreated, newly diagnosed disease. Trial registration UKALL 2011, EudraCT number 2010-020924-22; UKALL 2003, EudraCT number 2007-004013-34; UKALL14, EudraCT number 2009-012717-22.

Background and objective: Atrioventricular nodal reentry tachycardia is the commonest type of supraventricular tachycardia referred to the electrophysiology laboratory. It constitutes about two thirds of the supraventricular tachycardia admitted to the emergency department. The mechanism of this tachycardia is reentry. This study aimed to evaluate the efficacy of radiofrequency ablation therapy in atrioventricular nodal reentry tachycardia as the first line treatment using the conventional method. Methods: The standard technique for the electrophysiological study done to induce tachycardia. Three or four catheters were used. Atrial or ventricular programmed stimulation used to induce the tachycardia. Differentiation of the atrioventricular nodal reentry from atrial tachycardia and atrioventricular tachycardia done by ventricular entrainment. The dry ablation catheter of 4 mm tip used to modify the slow pathway. The appearance of junctional rhythm was a sign of the effective application of the radiofrequency application. The success of ablation was indicated by a failure to induce the tachycardia with repeated programmed stimulation. Results: Seventy patients with atrioventricular nodal reentry tachycardia were selected from total supraventricular tachycardia cases of 106 patients referred to the catheter lab for radiofrequency ablation. In 85% of the cases atrial programmed stimulation were used to induce the tachycardia and ventricular programmed stimulation and in 15% of the cases. Acute success rate was seen in 68 patients (97%). Conclusion: Catheter radiofrequency ablation is becoming technically easy, safe, and reliable as first line treatment in the majority of patients with atrioventricular reentry tachycardia.

Pulmonary mucoepidermoid carcinoma (PMEC) is a rare tumor with limited clinical data available due to its low incidence. So far, there are no universal treatment guidelines for this malignant tumor. We present here the case of a 59-year-old female never smoker who was initially referred to our hospital with cough and hemoptysis and was eventually diagnosed with PMEC. Based on further genetic testing, echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) fusion variants E20:A20 (V2) was found. The patient was treated with lorlatinib as the first-line treatment. This case is the first to describe the effectiveness of lorlatinib in treating an advanced high-grade PMEC with EML4-ALK fusion V2 mutation patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Cong and Liu.)

We analyzed demographic characteristics, comorbidities and patterns of treatment with tyrosine kinase inhibitors (TKIs) in a cohort of 3,633 incident cases of chronic myeloid leukemia (CML) identified across France from 1 January 2011 to 31 December 2014. Patients were identified through a specific algorithm in the French Healthcare Data System and were followed up 12 months after inclusion in the cohort. The estimated incidence rate of CML for this period in France was 1.37 per 100,000 person-years (95% Confidence Interval 1.36-1.38) and was higher in men, with a peak at age 75-79 years. At baseline, the median age of the cohort was 60 years (Inter Quartile Range 47-71), the Male/Female ratio was 1.2, and 25% presented with another comorbidity. Imatinib was the first-line TKI for 77.6% of the patients, followed by nilotinib (18.3%) and dasatinib (4.1%). Twelve months after initiation, 86% of the patients remained on the same TKI, 13% switched to another TKI and 1% received subsequently three different TKIs. During the follow-up, 23% discontinued and 52% suspended the TKI. Patients received a mean of 16.7 (Standard Deviation (SD) 9.6) medications over the first year of follow-up, and a mean of 2.7 (SD 2.3) concomitant medications on the day of first TKI prescription: 24.4% of the patients received allopurinol, 6.4% proton pump inhibitors (PPI) and 6.5% antihypertensive agents. When treatment with TKI was initiated, incident CML patients presented with comorbidities and polypharmacy, which merits attention because of the persistent use of these concomitant drugs and the potential increased risk of drug-drug interactions. [ABSTRACT FROM AUTHOR]

We analyzed demographic characteristics, comorbidities and patterns of treatment with tyrosine kinase inhibitors (TKIs) in a cohort of 3,633 incident cases of chronic myeloid leukemia (CML) identified across France from 1 January 2011 to 31 December 2014. Patients were identified through a specific algorithm in the French Healthcare Data System and were followed up 12 months after inclusion in the cohort. The estimated incidence rate of CML for this period in France was 1.37 per 100,000 person-years (95% Confidence Interval 1.36-1.38) and was higher in men, with a peak at age 75-79 years. At baseline, the median age of the cohort was 60 years (Inter Quartile Range 47-71), the Male/Female ratio was 1.2, and 25% presented with another comorbidity. Imatinib was the first-line TKI for 77.6% of the patients, followed by nilotinib (18.3%) and dasatinib (4.1%). Twelve months after initiation, 86% of the patients remained on the same TKI, 13% switched to another TKI and 1% received subsequently three different TKIs. During the follow-up, 23% discontinued and 52% suspended the TKI. Patients received a mean of 16.7 (Standard Deviation (SD) 9.6) medications over the first year of follow-up, and a mean of 2.7 (SD 2.3) concomitant medications on the day of first TKI prescription: 24.4% of the patients received allopurinol, 6.4% proton pump inhibitors (PPI) and 6.5% antihypertensive agents. When treatment with TKI was initiated, incident CML patients presented with comorbidities and polypharmacy, which merits attention because of the persistent use of these concomitant drugs and the potential increased risk of drug-drug interactions.

Background: Although current therapy for patients with early-stage squamous cell carcinoma of the head and neck (SCCHN) is potentially curative, the recurrence rate is high. Patients with recurrent or metastatic (R/M) SCCHN have a poor prognosis and substantial disease burden, including impaired health-related quality of life (HRQoL), productivity loss and indirect costs, such as need for caregiver support. The aim of this study was to characterize the impact of R/M SCCHN and its first-line treatment on patient and caregiver quality of life, daily activities and work productivity using real-world evidence from Europe.Methods: This was a multicentre retrospective study of patients with R/M SCCHN in France, Germany, Italy, Spain and the United Kingdom incorporating patient and caregiver surveys, and a physician-reported medical chart review, conducted between January and May 2019. Patients aged 18 or over with a physician confirmed diagnosis R/M SCCHN completed four validated measures of disease activity and its impact on quality of life and work productivity, while caregivers also completed questionnaire to assess the burden of providing care. Physicians provided data for clinical characteristics, patient management, testing history and treatment patterns.Results: A total of 195 medical/clinical oncologists provided data for 937, predominantly male (72%) patients, with almost half of patients aged over 65 years. The most frequently reported symptoms were fatigue (43%), weight loss (40%), pain (35%) and difficulty swallowing (32%). The EXTREME regimen was the most common first line therapy in over half of patients, who reported moderate or extreme pain/discomfort, and anxiety/depression, and problems with self-care resulting in a diminished health status compared with the general population. Only 14% were employed with high absenteeism or presenteeism, and over half of patients had a caregiver for whom the burden of care was substantial.Conclusion: Our results provide real-world insight into the multi-faceted burden associated with R/M SCCHN. The combination of poor HRQoL and the impairment in daily activities, social life and employment illustrates the wider impact of R/M SCCHN on patients and their caregivers, and highlights a need for novel 1 L treatment regimens to improve the humanistic and productivity burdens of this cancer. [ABSTRACT FROM AUTHOR]

Michele Ghidini,1 Claudio Pizzo,1 Andrea Botticelli,2 Jens Claus Hahne,3 Rodolfo Passalacqua,1 Gianluca Tomasello,1 Fausto Petrelli4 1Department of Oncology, Azienda Socio Sanitaria Territoriale of Cremona, Cremona, Italy; 2Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Rome, Italy; 3Division of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey, UK; 4Department of Oncology, Operative Unit of Oncology, Azienda Socio Sanitaria Territoriale of Bergamo Ovest, Treviglio, Bergamo, Italy Purpose: Incidence and mortality of biliary tract carcinoma (BTC) are increasing, especially in South America and Asia. Such a disease often bears a dismal prognosis because of diagnosis occurring at late stages and for the frequent relapses after surgery. The aims of this review were to summarize the state of the art of the treatment of BTC and give a view at possible future prospects linked with molecular profiling, immunotherapy, and targeted therapies. Design: We conducted a systematic literature search using MEDLINE and the 2018 ASCO Meeting abstract databases to identify published clinical trials, translational series, and meeting abstracts. All significant papers and abstracts available to date were included. Results: For resected BTC, thanks to the BILCAP study, adjuvant chemotherapy (CT) with capecitabine should be regarded as the new standard of care. For locally advanced inoperable and metastatic diseases, the use of chemoradiotherapy and radioembolization has not been supported by any randomized Phase III study. The standard of care remains the combination of CT with gemcitabine and cisplatin, as reported by the ABC-02 trial. All targeted therapies have failed to improve the survival outcomes, either in combination with CT or as single agents and are not recommended in the treatment of BTC. Whole-exome sequencing and molecular profiling have helped in identifying genetic signatures typical of different BTC subtypes. With this support, new trials with targeted agents and immunotherapy have been designed, and results are awaited. Conclusion: BTC still remains a disease with very few treatment options. Different BTC subtypes own peculiar gene mutations and pathways alterations. Therefore, molecular profiling may be the only key to enable new tailored strategies with targeted agents and immunotherapy. Keywords: surgery, cholangiocarcinoma, adjuvant treatment, first-line treatment, targeted therapies, molecular profiling

Background: Rituximab has become one of the first-line therapies for the treatment of moderate and high-risk primary membranous nephropathy (pMN). We retrospectively reviewed 95 patients with pMN who received rituximab therapy and focused on the therapeutic effects and safety of this therapy in a Chinese cohort.Methods: Ninety-five consecutive patients with pMN diagnosed by kidney biopsy received rituximab and were followed up for >6 months. Four weekly doses of rituximab (375 mg/m2) was adopted as the initial administration. Repeated single infusions were administrated to maintain B cell depletion levels of

Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms “immunotherapy” and “chemotherapy”. 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77–0.92), PFS (HR 0.80, 0.75–0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20–5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%–49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels.Systematic Review RegistrationPROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678).

Objective: As compared to whites, the black population develops hypertension (HTN) at an earlier age, has a greater frequency and severity of HTN, and has poorer control of blood pressure (BP). Traditional practices and treatment efforts have had minor impact on these disparities, with over a 2-fold higher death rate currently for blacks as compared to whites. The University of Mississippi Medical Center (UMC) is located in the southeastern US and the Stroke Belt, which has higher rates of HTN and related diseases as compared to the rest of the country.Methods: We retrospectively analyzed the UMC's Research Data Warehouse, containing >30 million electronic health records from >900,000 patients to determine the initial BP response following the first prescribed antihypertensive drug.Results: There were 5,973 white (45% overall HTN prevalence) and 10,731 black (57% overall HTN prevalence) patients who met criteria for the study. After controlling for age, BMI, and drug dosage, black males were overall less likely to have controlled BP (defined as < 140/90 mmHg) and were associated with smaller falls in BP as compared to whites and black females. Blockers of the renin-angiotensin system (RAS) failed to significantly improve odds of HTN control vs. the untreated group in black patients. However, our data suggests that these drugs do provide significant benefit in blacks when combined with THZ, as compared to untreated and as compared to THZ alone.Conclusion: These data support the use of a single-pill formulation with ARB or ACE inhibitor with a thiazide in blacks for initial first-line HTN therapy and suggests that HTN treatment strategies should consider both race and gender. Our study gives a unique insight into initial antihypertensive responses in actual clinical practice and could have an impact in BP control efficiency in a state with prevalent socioeconomic and racial disparities.

Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms "immunotherapy" and "chemotherapy". 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77–0.92), PFS (HR 0.80, 0.75–0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20–5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%–49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels. Systematic Review Registration: PROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678). [ABSTRACT FROM AUTHOR]

Background/aim: Immune thrombocytopenia (ITP) is treated by corticosteroids and/or intravenous immune globulin as the first line treatment when necessary. Mean platelet volume (MPV) is a marker of platelet production and function. In this study, we aimed to search the relationship between the MPV and the treatment response in ITP patients and it was hypothesized that MPV can be used as a predictor of the response. Materials and methods: The 70 newly diagnosed adult primary ITP patients and 70 of healthy people were included. MPV between ITP and healthy population, MPV in the diagnosis and after the treatment between the responders and the nonresponders were compared. Results: The responders had significantly higher MPV and the nonresponders had significantly lower MPV than the healthy population (11.09 and 10.21 fL, P = 0.03; 9.38 and 10.21 fL, P = 0.001). MPV in the diagnosis was significantly higher in the responders than the nonresponders (11.09 and 9.38 fL, P = 0.005). MPV significantly changed after the treatment in the responders (11.09 to 9.32 fL, P = 0.004). Conclusion: MPV can be used as a predictor of early response to the first line treatment in newly diagnosed adult primary ITP patients. [ABSTRACT FROM AUTHOR]

Background: L-asparaginase is a key component of treatment for patients with acute lymphoblastic leukaemia (ALL) in the UK. Commonly used forms of asparaginase are native E. coli-derived asparaginase (native asparaginase) and pegaspargase in first-line combination therapy, and native Erwinia chrysanthemi-derived asparaginase (Erwinia asparaginase) as second-line treatment. The objective of this study was to evaluate the cost-effectiveness of pegaspargase versus native asparaginase in first-line combination therapy for patients with newly diagnosed ALL. A combined decision tree and health-state transition Markov cost-effectiveness model was developed to assess the relative costs and health outcomes of pegaspargase versus native asparaginase in the UK setting. Results: In base case analyses, first-line pegaspargase (followed by Erwinia asparaginase in cases of hypersensitivity) dominated first-line native asparaginase followed by Erwinia asparaginase; i.e. resulted in lower costs and more quality-adjusted life year gain. The favourable hypersensitivity rates and administration profile of pegaspargase led to lifetime cost savings of £4741 versus native asparaginase. Pegaspargase remained cost-effective versus all treatment strategies in all scenario analyses, including use of the 2500 IU/m2 dose, recommended for patients ≤21 years of age. Conclusions: Pegaspargase, as part of multi-drug chemotherapy, is a cost-effective option for the treatment of newly diagnosed ALL. Based on this study, The National Institute for Health and Care Excellence Technology Appraisal Committee concluded that it could recommend pegaspargase as a cost-effective use of National Health Service resources in England & Wales for treating ALL in children, young people and adults with untreated, newly diagnosed disease. Trial registration: UKALL 2011, EudraCT number 2010-020924-22; UKALL 2003, EudraCT number 2007-004013-34; UKALL14, EudraCT number 2009-012717-22. [ABSTRACT FROM AUTHOR]

Treatment of metastatic clear cell renal carcinoma (mccRCC) has changed dramatically over the past 20 years, without improvement in the development of biomarkers. Recently, circulating tumor cells (CTCs) have been validated as a prognostic and predictive tool for many solid tumors. We evaluated CTCs in blood samples obtained from patients diagnosed with mccRCC. Comparisons of CTC counts, protein expression profiling, and DNA mutants were made in relation to overall survival and progression-free survival. CTCs were isolated from 10 mL blood samples using the ISET® system (Isolation by SizE of Tumor Cells; Rarecells, France) and counted. Protein expression was evaluated in immunocytochemistry assays. DNA mutations were identified with next generation sequencing (NGS). Blood samples (10 mL) were collected from 12 patients with mccRCC before the start of first-line systemic therapy, and again 30 and 60 days after the start of treatment. All 12 patients had CTCs detected at baseline (median, 1.5 CTCs/mL; range: 0.25–7.75). Patients with CTC counts greater than the median had two or more metastatic sites and exhibited worse progression-free survival (19.7 months) compared to those with CTC counts less than the median (31.1 months). Disease progression was observed in 7/12 patients during the study. Five of these patients had baseline CTC counts greater than the median, one had higher CTC levels at the second blood collection, and one patient had CTCs present at 1 CTC/mL which positively stained for PD-L1, N-cadherin, VEGF, and SETD2. CTC DNA from six patients with worse outcomes was subjected to NGS. However, no conclusions could be made due to the low variant allele frequencies. Detection of CTCs in patients with mccRCC receiving first-line treatment is a feasible tool with prognostic potential since increased numbers of CTCs were found to be associated with metastasis and disease progression. [ABSTRACT FROM AUTHOR]

Immunotherapy has dramatically changed the therapeutic scenario in treatment naïve advanced non-small cell lung cancer (NSCLC). While single agent pembrolizumab has become the standard therapy in patients with PD-L1 expression on tumor cells ≥ 50%, the combination of pembrolizumab or atezolizumab and platinum-based chemotherapy has emerged as an effective first line treatment regardless of PD-L1 expression both in squamous and non-squamous NSCLC without oncogenic drivers. Furthermore, double immune checkpoint inhibition has shown promising results in treatment naïve patients with high tumor mutational burden (TMB). Of note, the presence of both negative PD-L1 expression and low TMB may identify a subgroup of patients who has little benefit from immunotherapy combinations and for whom the best treatment option may still be platinum-based chemotherapy. To date, first-line single agent immune checkpoint blockade has demonstrated limited activity in EGFR mutated NSCLC and the combination of immunotherapy and targeted agents has raised safety concerns in both EGFR and ALK positive NSCLC patients. Finally, in EGFR mutated or ALK rearranged NSCLC, atezolizumab in combination with platinum-based chemotherapy and bevacizumab is emerging as a potential treatment option upon progression to first line tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]

Summary: To assess efficacy of radioimmunotherapy (RIT) in follicular lymphoma, data from 281 patients collected in the RIT Network, with a median follow‐up of 8·2 years after RIT were analysed. RIT was given at first line in 18·5% and at relapse in 81·5%. Following first line therapy, 76·9% achieved complete remission (CR), 9·6% partial remission (PR), 1·9% stable disease (SD) and 1·9% had progressive disease (PD); response was not documented in 9·7%. At relapse, the rate of CR was 48·5% and that of PR was 16·6%, SD 2·6% and PD 10·5%; response was not documented in 21·8%. After median follow‐up of 8·2 years, median progression‐free survival (PFS) for all was 2·54 years, median overall survival (OS) was not reached. Median PFS and OS (both not reached) were significantly better in first line, compared to RIT at relapse (PFS, 2·11 years; OS, 10·8 years; P = 0·0037 and P = 0·0021, respectively). Overall 8‐year PFS was 33·9%, 53·6% for first line and 29·6% for relapsed individuals. Overall 8‐year OS was 58·8%, 78·1% for first line and 54·5% for relapsed patients. Thirty‐five patients (12·5%) developed secondary malignancy and 16 patients (5·7%) experienced transformation into aggressive lymphoma. RIT is a safe and effective treatment option for follicular lymphoma, both at front line and relapse with an 8‐year PFS of 53·6% and 29·6%, respectively. [ABSTRACT FROM AUTHOR]

Opinion Statement: Soft tissue sarcomas are rare cancers with an expected incidence of about 14,000 new cases in 2018, and account for less than 1% of all cancers. It includes in excess of 75 heterogeneous subtypes with varying biology, molecular aberrations, and variable response to treatment. Because of the rarity of these tumors and the many different subtypes, there is no large-scale data to guide treatment, and hence the need for a multidisciplinary individualized approach to treatment, preferably at a high-volume tertiary referral center. For localized disease, surgery with or without radiation is the preferred treatment. In metastatic disease, the longest track record is with use of anthracyclines, either alone or in combination with ifosfamide, but the median overall survival even with combination was just over a year. There have been recent advances in understanding the heterogeneity of these tumors and the need for an individualized approach. With that new knowledge, recent approvals of trabectedin, eribulin, and pazopanib have been limited to some select histologic subtypes with improved outcomes. More recently, immunotherapy has been tested in select histotypes of sarcoma with encouraging activity and has led to further evaluation in combination with immunotherapeutic agents, as well as with chemotherapy and radiation treatments. Here, in this article, we summarize the data of the currently approved therapies in metastatic soft tissue sarcoma, with the principal focus on first-line therapies. We also review the recent encouraging data with PDGFR-targeted antibody (olaratumab) with doxorubicin which showed an impressive improvement in overall survival in phase II study. Molecular characterization of sarcoma subtypes will likely improve understanding of these very diverse tumors and improve target characterization. The ongoing efforts in better understanding these rare tumors hold the key to make a difference in the outcome of these patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Whether patients with RAS mutation metastatic colorectal cancer (mCRC) obtain benefits from bevacizumab added to first-line chemotherapy remains unclear. Methods: PubMed, Cochrane Systematic Reviews, the Cochrane Collaboration Central Register of Controlled Clinical Trials, ClinicalTrials.gov, and the American Society of Clinical Oncology and European Society for Medical Oncology databases were searched to identify abstracts for randomized controlled trials (RCTs) evaluating the efficacy of bevacizumab for the first-line treatment of patients with RAS mutations mCRC from inception to the end of April 2016. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were estimated. Results: Ten eligible papers reporting six RCTs were included. In the network meta-analysis of patients with RAS mutations, bevacizumab + chemotherapy prolonged PFS compared with chemotherapy alone (HR 0.75, 95% CI 0.51-1.10), but the difference was not statistically significant. Bevacizumab + chemotherapy did not prolong OS compared with chemotherapy alone (HR 1.10, 95% CI 0.73-1.66). Conclusion: There was insufficient evidence to definitively state that patients with RAS mutations mCRC could benefit from bevacizumab combined with chemotherapy as first-line treatment.