Second-line Treatment Regimens Research Articles

Prevalence, rate, and predictors of virologic failure among adult HIV-Infected clients on second-line antiretroviral therapy (ART) in Tanzania (2018–2020): a retrospective cohort study

BackgroundAntiretroviral therapy (ART) has been proven to be highly effective in reducing the impact of human immunodeficiency virus (HIV) infection. However, as more people receive initial ART treatment, the risk of developing resistance and eventual treatment failure increases, leading to the need for second-line treatment regimens. Understanding the factors that contribute to virologic failure to second-line ART is crucial in preventing switching to the more expensive and toxic third-line regimens. This study provides information on the prevalence, rate, and predictors of virologic failure (VF) among clients on second-line ART in Tanzania.ResultsWe followed 4718 clients for 15100 person-years (PY) of observations. Of them, 1402 (29.72%) experienced virologic failure at a rate of 92.85 per 1000 PY of observations (95% CI 88.11, 97.84). Factors that were associated with VF included: having a viral load count of ≥ 1000 copies/mL during first-line ART, with a hazard ratio (HR) 4.65 (95% CI 3.57, 6.07), using lopinavir (LPV/r) as a protease inhibitor during second-line ART (HR 4.20 (95% CI 3.12, 7.10), having a CD4 count < 200 cells/mm3 during second-line ART (HR 1.89 (95% CI 1.46, 2.44), and being on ART for 13–35 months (HR 8.22 (95% CI 2.21, 30.61). Paradoxically, having a CD4 count < 200 cells/mm3 during first-line ART treatment was associated with a reduced risk of virologic failure (HR 0.77 (95% CI 0.60, 0.99).ConclusionsIn Tanzania, approximately 30% of adult clients on second-line ART experience VF at a rate of 92.71 per 1000 person-years. This high virologic failure rate underscores the urgent need for targeted interventions, such as enhancing adherence support, optimizing drug regimens, and regular viral load monitoring. These interventions will reduce the need for switching to the more costly and toxic third-line ART therapy and are also crucial for achieving the UNAIDS goal of 95% viral suppression among treated individuals by 2030.

Utilizing an acute hyperthermia-induced seizure test and pharmacokinetic studies to establish optimal dosing regimens in a mouse model of Dravet syndrome.

The current standard of care for Dravet syndrome (DS) includes polytherapy after inadequate seizure control with one or more monotherapy approaches. Treatment guidelines are often based on expert opinions, and finding an optimal balance between seizure control and adverse drug effects can be challenging. This study utilizes the efficacy and pharmacokinetic assessment of a second-line treatment regimen that combines clobazam and sodium valproate with an add-on drug as a proof-of-principle approach to establish an effective therapeutic regimen in a DS mouse model. We evaluated the efficacy of add-on therapies stiripentol, cannabidiol, lorcaserin, or fenfluramine added to clobazam and sodium valproate against hyperthermia-induced seizures in Scn1aA1783V/WT mice. Clobazam, N-desmethyl clobazam (an active metabolite of clobazam), sodium valproate, stiripentol, and cannabidiol concentrations were quantified in plasma and brain using liquid chromatography-tandem mass spectrometry for the combinations deemed effective against hyperthermia-induced seizures. The concentration data were used to calculate pharmacokinetic parameters via noncompartmental analysis in Phoenix WinNonLin. Higher doses of stiripentol or cannabidiol, in combination with clobazam and sodium valproate, were effective against hyperthermia-induced seizures in Scn1aA1783V/WT mice. In Scn1aWT/WT mice, brain clobazam and N-desmethyl clobazam concentrations were higher in the triple-drug combinations than in the clobazam monotherapy. Stiripentol and cannabidiol brain concentrations were greater in the triple-drug therapy than when given alone. A polypharmacy strategy may be a practical preclinical approach to identifying efficacious compounds for DS. The drug-drug interactions between compounds used in this study may explain the potentiated efficacy of some polytherapies.

Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib

IntroductionFor patients with advanced epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) who progress on first-line osimertinib, the optimal second-line treatment regimen after progression is not known. We sought to assess practice patterns and evaluate the association between different therapies and survival in patients with EGFR-mutated NSCLC following progression on first-line osimertinib. MethodsRetrospective cohort study of patients who received first-line treatment with osimertinib using a population-based, multicenter nationwide electronic health record-derived deidentified database. ResultsWe identified 2373 patients who received first-line osimertinib. The majority (n = 2279) received osimertinib monotherapy. A total of 538 patients received first-line osimertinib and had second-line treatment data available. Second-line treatment regimens were varied: 65% (n = 348) included chemotherapy, 37% (n = 197) included an immune checkpoint inhibitor (ICI), and 44% (n = 234) included an EGFR tyrosine kinase inhibitor (TKI).We then analyzed the 333 patients with PS 0-2 who received chemotherapy with osimertinib (n = 107, 32%) versus chemotherapy without osimertinib (n = 226, 68%). The continuation of osimertinib with chemotherapy was associated with superior PFS (median: 10.1 versus 5.9 months, Hazard Ratio [HR]: 0.48, 95% Confidence Interval [CI]: [0.34, 0.68], P < .001) and overall survival (OS) (median: 17.0 versus 12.8 months, HR: 0.64, 95% CI: [0.44, 0.93], P = .018) compared to other chemotherapy approaches without osimertinib. This effect was most pronounced in patients with an EGFR exon 19 deletion. ConclusionsFollowing progression on osimertinib, a wide variety of treatment regimens were used. The continuation of osimertinib with chemotherapy in the second line was associated with increased PFS and OS.

74P Real-world progression-free and overall survival of patients with metastatic colorectal cancer according to first and second-line treatment regimen: PROMETCO study

74P Real-world progression-free and overall survival of patients with metastatic colorectal cancer according to first and second-line treatment regimen: PROMETCO study

Retrospective study of continued immunotherapy in patients with advanced esophageal squamous cell carcinoma after progression on first-line immunotherapy combination chemotherapy.

e16025 Background: Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced esophageal squamous cell carcinoma. However, the disease progression pattern after first-line immunotherapy resistance and the second-line treatment options are not fully understood. This retrospective study was designed to explore the efficacy of continued immunotherapy in advanced esophageal squamous cell carcinoma patients after progression on first-line immunotherapy combination chemotherapy. Methods: We retrospectively analyzed the efficacy of second-line continued immunotherapy in patients with stage IV esophageal squamous cell carcinoma who experienced disease progression after first-line immunotherapy at Huai 'an First People's Hospital from July 2020 to December 2023. The main outcome were progression-free survival (PFS), 3-and 6-month PFS rates, objective response rate (ORR), disease control rate(DCR)and overall survival (OS). Results: A total of 30 eligible patients were included. Median age was 67 years, 20 (66.7%) patients were male. 14 patients achieved partial response (PR), 8 stable disease (SD), illustrating an ORR of 46.7% and a DCR of 73.3%. Median PFS was 3.85 months. In the second-line treatment regimen, 21 (70%) were immunotherapy combined chemotherapy, and the others were immunomonotherapy or combined anti-angiogenic drugs. Conclusions: The current retrospective data shows that a considerable number of patients still could benefit from second-line immunotherapy after the progress of first-line immunotherapy in patients with advanced ESCC. This result brings new hope for the increasingly large population of immune resistance esophageal cancer patients. [Table: see text]

A single-arm, open-label phase II clinical trial of SHR-1210 (camrelizumab) in combination with nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma.

e16007 Background: The prognosis of advanced esophageal cancer is bleak, and the current first-line regimen based on paclitaxel, cisplatin and fluorouracil (TPF) with an effective rate is about 30%. The second-line treatment regimen based on anti-PD-1/PD-L1 monoclonal antibodies obtained median overall survival (mOS) 10.8 months in phase I-II clinical trials, but a large proportion of patients (pts) still do not respond to this therapy. Additionally, nimotuzumab in the previous Cuba phase 2 study had a good disease control rate (DCR) combined with PF regimen. So, we conducted the study to evaluate the new combination modality efficacy and treatment-related adverse events (safety). The primary endpoints was ORR, and the secondary endpoints included overall survival (OS), DCR, progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the second-line treatment for ORR is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha=0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached CR/PR. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase 2 study, a total of 41 pts were administered. One case was lost to follow-up. The mean age was 45 years (range, 42-77). The results of the intention-to-treat analysis showed that the ORR was 36% (15/42). The mOS was 12.62 months with median follow-up 8.28 months. The 9-month and 12-month survival rates were 84% and 51%, respectively. The DCR was 81% (34/42). Median PFS was 9.89 months with median follow-up 9.17 months. In terms of safety, the incidence of TEAEs was 60% (25/42), of which 71% (30/42) had adverse events below grade 3 and 26% (11/42) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 10% (4/42), of which 0 case related to nimotuzumab and 4 cases related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma showed a trend benefit for ORR and OS with a controllable toxicity.

The prognostic value of colonoscopy grading for acute graft-versus-host disease in patients with malignant hematological disorders after unrelated cord blood transplantation

Objective: To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) . Methods: Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients' prognosis. Results: Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy (P<0.001), 81.5% and 39.1% at 56 days after colonoscopy (P=0.002), with optimal effective rate of 92.6% and 65.2% (P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant (P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients' age were independent risk factors for survival. Conclusion: The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Association between Glucose-lowering Treatments and Risk of Diabetic Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study.

Glycaemic variability is possibly linked to the development of diabetic retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce glycaemic variability. This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes. A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes. Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium-glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated. Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Efficacy and Safety of Docetaxel plus Ramucirumab for Patients with Pretreated Advanced or Recurrent Non-small Cell Lung Cancer: Focus on Older Patients.

Combination therapy with docetaxel (DTX) and ramucirumab (RAM) has been used as a second-line treatment for advanced or recurrent lung cancer. However, there is insufficient evidence regarding the safety of angiogenesis inhibitors in older patients. This multicenter retrospective study aimed to investigate the efficacy and safety of second-line treatment regimens in older patients with advanced or recurrent non-small cell lung cancer (NSCLC). We retrospectively analyzed 145 patients aged ≥70 years with advanced or recurrent NSCLC treated with second-line chemotherapy after platinum-based therapy between April 1, 2016, and March 31, 2021. Patients were subdivided into the DTX + RAM (n=38) and single-agent (n=107) groups. The median time to treatment failure was 6.3 months (95% confidence interval [CI] 3.6-9.6) in the DTX + RAM group and 2.3 months (95% CI 1.7-3.0) in the single-agent group (p < 0.01). The median overall survival was 15.9 months (95% CI 12.3-NotAchieved) in the DTX + RAM group and 9.4 months (95% CI 6.9-15.1) in the single-agent group (p = 0.01). Grade ≥ 3 adverse events frequency was not significantly different between the two groups, except for edema. Patients in the DTX + RAM group who did not discontinue treatment owing to adverse events exhibited the most favorable prognosis. These findings suggest that the DTX + RAM combination is an effective second-line therapy for older patients with advanced or recurrent NSCLC, offering favorable efficacy without treatment discontinuation owing to adverse events.

Efficacy and Prognosis of Chemotherapy Regimen Containing BTK Inhibitor in Treatment of Recurrent/Refractory Mantle Cell Lymphoma

To investigate the efficacy and prognosis of chemotherapy regimen containing Bruton's tyrosine kinase (BTK) inhibitor in the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL). The clinical data of 134 patients with R/R MCL were collected and analyzed retrospectively. The clinical characteristics of patients and effect of chemotherapy regimen on efficacy, overall survival (OS) and progression-free survival (PFS) were observed. The median age of the patients was 58(56-61) years old, and male to female ratio was about 2.9∶1. Patients with Ann Arbor stage III-IV accounted for 77.6%, extranodal involvement > 2 for 43.3%, bone marrow involvement for 60.4%, gastrointestinal involvement for 24.6%, and hepatosplenomegaly for 38.1%. The median follow-up time was 30 (2-103) months, overall response rate (ORR) was 41.8%, 3-year PFS was not reached, and 3-year and 5-year OS rate was 62.7% and 53.8%, respectively. The ORR of BTK inhibitor group was 56.9%, which was higher than 32.5% of non-BTK inhibitor group (P =0.006). The difference was statistically significant in PFS between the two groups (P =0.002), but was not in OS (P>0.05). The difference was statistically significant in OS between classical and special morphology (P < 0.001), but was not in PFS (P >0.05). Ki-67 was an influencing factor for OS and PFS. Multivariate analysis showed that Ki-67, B symptoms, MIPI score, and Ann Arbor stage were independent prognostic factors affecting patients' OS. The second-line treatment regimen was an independent prognostic factor affecting patients' PFS. The chemotherapy regimen containing BTK inhibitors can effectively improve the efficacy and prolong the PFS of R/R MCL patients. Ki-67, B symptoms, MIPI score, and Ann Arbor stage are independent prognostic factors for R/R MCL patients.

Clinical outcomes with second-line dolutegravir in people with virological failure on first-line non-nucleoside reverse transcriptase inhibitor-based regimens in South Africa: a retrospective cohort study

Dolutegravir (DTG) is recommended for second-line antiretroviral therapy (ART) after virological failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in people living with HIV in low-income and middle-income countries. We compared the effectiveness of DTG versus the previously recommended ritonavir-boosted lopinavir (LPV/r) regimen for second-line treatment in South Africa. In this retrospective observational cohort study, we used routinely collected, de-identified data from 59 primary health-care facilities in eThekwini Municipality, KwaZulu-Natal, South Africa. We included people living with HIV aged 15 years or older with virological failure (defined as two consecutive viral loads of ≥1000 copies per mL at least 56 days apart) on first-line NNRTI-based ART containing tenofovir disoproxil fumarate (TDF) and who switched to second-line ART. Our primary outcomes were retention in care and viral suppression (<50 copies per mL) at 12 months after starting second-line treatment. We used modified Poisson regression models to compare these outcomes between second-line regimens (zidovudine [AZT]/emtricitabine or lamivudine [XTC]/DTG; TDF/XTC/DTG; and AZT/XTC/LPV/r). We included 1214 participants in our study, of whom 729 (60%) were female and 485 (40%) were male, and whose median age was 36 years (IQR 30-42). 689 (57%) were switched to AZT/XTC/LPV/r, 217 (18%) to AZT/XTC/DTG, and 308 (25%) to TDF/XTC/DTG. Compared with AZT/XTC/LPV/r (75%), retention in care was higher with AZT/XTC/DTG (86%, adjusted risk ratio [aRR]=1·14, 95% CI 1·03-1·27; adjusted risk difference [aRD]=10·89%, 95% CI 2·01 to 19·78) but similar with TDF/XTC/DTG (77%, aRR=1·01, 0·94-1·10; aRD=1·04%, -5·03 to 7·12). Observed retention in care was lower with TDF/XTC/DTG than with AZT/XTC/DTG, although in multivariable analysis evidence for a difference was weak (aRR=0·89, 0·78-1·01, p=0·060; aRD=-9·85%, -20·33 to 0·63, p=0·066). Of 799 participants who were retained in care with a 12-month viral load test done, viral suppression was higher with AZT/XTC/DTG (59%; aRR=1·25, 1·06-1·47; aRD=11·57%, 2·37 to 20·76) and higher with TDF/XTC/DTG (61%; aRR=1·30, 1·14-1·48; aRD=14·16%, 7·14 to 21·18) than with AZT/XTC/LPV/r (47%). These findings from routine care support further implementation of WHO's recommendation to use DTG instead of LPV/r in people living with HIV who experience virological failure while receiving first-line NNRTI-based ART. Bill & Melinda Gates Foundation. For the isiZulu translation of the abstract see Supplementary Materials section.

Is There Room for Liposomal Irinotecan in Biliary Tract Cancer? A Meta-analysis of Randomised Trials

AimsThe combination of 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin (FOLFOX) is widely acknowledged as the standard regimen for second-line treatment in patients with advanced biliary tract cancer. Nanoliposomal irinotecan (nal-IRI) has demonstrated its activity in patients with advanced pancreatic cancer. Recent studies have investigated the activity of nal-IRI in combination with 5-FU/LV for biliary tract cancer. However, the results have been contradictory. We conducted a meta-analysis to assess survival outcomes and response rates in randomised trials investigating the activity of nal-IRI in previously treated biliary tract cancer patients. Materials and methodsWe systematically collected potentially relevant findings from PubMed/Medline, the Cochrane library and EMBASE. Abstracts presented at major international oncological meetings were also reviewed. We extracted hazard ratios and 95% confidence intervals for progression-free survival and overall survival, as well as odds ratios and 95% confidence intervals for objective response rate. The outcomes of the accessible randomised studies evaluating the activity of nal-IRI plus 5-FU/LV were analysed. ResultsThe combination therapy exhibited a statistically significant decrease in the risk of progression (hazard ratio 0.70; 95% confidence interval 0.50–0.97) when compared with 5-FU/LV alone. Additionally, the dual regimen yielded longer overall survival and a higher objective response rate. ConclusionOur meta-analysis showed that nal-IRI plus 5-FU/LV had a superior activity in comparison with 5-FU/LV. Further investigations are required to elucidate the role of nal-IRI in this setting and to identify subgroups of patients who could derive the greatest benefit from its administration.

A Bedaquiline, Pyrazinamide, Levofloxacin, Linezolid, and Clofazimine Second-line Regimen for Tuberculosis Displays Similar Early Bactericidal Activity as the Standard Rifampin-Based First-line Regimen.

In 2018 the World Health Organization recommended a switch to an all oral bedaquiline-based second-line regimen for treatment of drug-resistant tuberculosis (DR-TB). How these new second-line regimens fare in comparison to first-line regimens for treatment of drug-sensitive tuberculosis (DS-TB) is not well known. In this study, we contemporaneously enrolled subjects with DS-TB (n = 31) or DR-TB (n = 23) and assessed their response to therapy with first-line (rifampin, isoniazid, ethambutol, pyrazinamide) or second-line (bedaquiline, pyrazinamide, levofloxacin, linezolid, clofazimine) regimens, respectively. We found that the early bactericidal activity of first- and second-line regimens was similar during the first 2 weeks of therapy as determined by BACTEC MGIT, colony-forming units, and a liquid limiting dilution assay capable of detecting differentially detectable/culturable Mycobacterium tuberculosis. Furthermore, an identical percentage (77.8%) of subjects from the DS-TB and DR-TB cohorts converted to culture negative after 2 months of therapy. Despite presenting with more advanced disease at time of treatment, subjects with DR-TB receiving an all oral bedaquiline-based second-line treatment regimen displayed a similar microbiological response to therapy as subjects with DS-TB receiving a first-line treatment regimen.

Real-World Evaluation of Treatment Discontinuation and Healthcare Resource Utilization in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Introduction: Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are the most prevalent types of leukemia in the United States. Given the emergence of novel CLL/SLL therapies, it is important to understand real-world treatment characteristics and unmet needs. The objectives of this retrospective cohort study were to examine patient characteristics, treatment patterns, and associated outcomes for patients with CLL/SLL, overall, and by CLL and SLL, respectively. Methods: A retrospective study was conducted using Symphony Integrated Dataverse (IDV ®), a comprehensive, longitudinal, open-claims database, and integrated electronic medical record data. Patients aged ≥18 years with ≥1 diagnosis for CLL or SLL and who initiated a first-line or second-line treatment between January 1, 2020, and December 31, 2022 (index period) were included in the study. Index date was defined as the date of treatment initiation. Patients were required to be continuously enrolled for 365 days prior to the index date and ≥90 days following the index date. Patient data were included until patients were lost to follow-up or to the end of the study period (March 31, 2023). Treatment patterns were examined with the following treatment regimens and stratified by line of therapy: chemotherapy (including bendamustine-based and other chemotherapy), anti-CD20-based, Bruton tyrosine kinase inhibitors (BTKiibrutinib- and acalabrutinib-based), and venetoclax-based therapy. Zanubrutinib use was not captured in the BTKi treatment category as its CLL/SLL indication approval date (January 19, 2023) was outside the index period. Discontinuation rate was defined as the percentage of patients who discontinued their current treatment regimen within 90 days. Healthcare resource utilization was measured by number of outpatient visits, inpatient visits, and other medical/hospital services per patient per month (PPPM) during the treatment regimen. Results:There were 17,748 and 5,667 patients with CLL/SLL who initiated a first-line or second-line treatment regimen during the index period, respectively. The most frequently used treatment regimens in first line were BTKi (49.9%), followed by anti-CD20 (26.1%), venetoclax (15.4%), and chemotherapy (8.6%). BTKi continued to be the predominant treatment (49.6%) in second line, followed by venetoclax (30.9%), chemotherapy (10.4%), and anti-CD20 (9.2%). First-line patients treated with BTKi regimens were older and Medicare-insured when compared with patients receiving venetoclax-based regimens (65+ years: 77.1% vs 66.9%, P-value &amp;lt;0.001; Medicare: 61.7% vs 53.0%, P-value &amp;lt;0.001). Patients receiving BTKi had significantly lower discontinuation rates compared with other treatment regimens during both first and second lines of therapies (Figure 1). Mean PPPM outpatient visits, inpatient visits, and other medical/hospital services were less frequent with BTKi therapies vs other treatment regimens across both lines of therapy (Table 1). Of the 17,748 patients initiating first line of therapy, 13.3% had SLL while the remaining 86.7% had CLL. The proportion of patients with SLL vs CLL decreased in second line and second line or later (8.0% vs 92.0% and 6.8% vs 93.2%, respectively). Treatment discontinuation rate in SLL patients was higher than that in CLL patients in first line (32.41% and 25.08%, respectively); however, discontinuation rates became comparable with later lines of therapy. Across all lines of therapy, healthcare resource utilization was significantly higher in SLL patients than CLL patients. Median PPPM outpatient visits were 1.02 for SLL and 0.67 for CLL. Median PPPM for other medical/hospital services was 0.7 for SLL and 0.23 for CLL. Conclusions: BTKi therapy, the primary treatment regimen across first- and second-line therapies, has significantly lower discontinuation rate and healthcare resource utilization compared with other treatment regimens. Further studies are needed to evaluate real-world clinical outcomes of CLL/SLL regimens to support evidence-based treatment decisions.

Small molecule multitarget antiangiogenic inhibitor treatments for advanced thymic epithelial tumors: A retrospective study.

Thymic epithelial tumors (TETs) are rare malignant tumors with limited treatment options. No established second-line treatment regimen is available following the preferred first-line chemotherapy, resulting in unsatisfactory efficacy and poor prognosis for patients with advanced TETs. This study aimed to evaluate the efficacy of small molecule multitarget antiangiogenic inhibitors as well as the prognostic factors for advanced TETs. A retrospective study was conducted using data from a real-world database. Clinical information and survival follow-up data were collected from 52 patients with advanced TETs who received small molecule multitarget antiangiogenic inhibitors at Zhejiang Cancer Hospital between August 10, 2016 and August 10, 2022. The short-term efficacy of the treatments, survival time of the patients, and relevant prognostic factors of advanced TETs were analyzed. Out of the 52 patients included in this study, 16 had thymoma and 36 had thymic carcinoma. The 52 patients had an overall response rate of 21.1% and a disease control rate of 94.2%. In addition, the median progression-free survival (PFS) was 8.05 months, and the overall survival (OS) was 25.00 months. Apatinib was given to 33 patients, anlotinib to 15 patients, and sunitinib or lenvatinib to four patients. Only seven patients received antiangiogenic inhibitors as their first-line therapy, 27 patients as their second-line therapy, and 18 patients as third-line or subsequent therapy. Meanwhile, 42 patients received monotherapy with an antiangiogenesis inhibitor, while 10 patients received combination therapy. Univariate analysis indicated that the combined treatment was associated with a superior OS (p = 0.044); multivariate analysis indicated that the combined treatment was an independent prognostic factor for PFS (p = 0.014) and OS (p = 0.012). The findings suggest that small molecule multitarget antiangiogenic inhibitors are efficacious as second or post-line treatments as a viable alternative treatment option for patients with advanced TETs.

Influence of treatment intensity and medical comorbidities in older adults with peripheral T cell lymphoma

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71–83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N = 732), and 23.8% for patients treated with non-anthracycline-containing regimens (N = 105; p < 0.001). In patients without comorbidities, CHOEP remained independently associated with improved OS (HR 0.52, 95% CI,0.30-0.91). Median OS was 1.2 years from initiation of second-line therapy (N = 228) independent of treatment regimen. Frontline but not second-line treatment regimen is associated with OS in older patients with PTCL.

Ramucirumab plus FOLFIRI as second-line treatment for patients with RAS wild-type metastatic colorectal cancer previously treated with anti-EGFR antibody: JACCRO CC-16

Chemotherapy in combination with anti-epidermal growth factor receptor (EGFR) antibody is considered a first-line treatment regimen for RAS wild-type and left-sided metastatic colorectal cancer (mCRC), whereas second-line treatment regimens have not yet been established. Few studies have prospectively evaluated second-line treatment with anti-vascular endothelial growth factor antibody after first-line anti-EGFR antibody therapy for RAS wild-type mCRC. This non-randomized phase II trial investigated the clinical outcomes of second-line ramucirumab (RAM) plus fluorouracil, levofolinate, and irinotecan (FOLFIRI) after first-line anti-EGFR antibody in combination with doublet or triplet regimen in patients with RAS wild-type mCRC. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were PFS, overall survival (OS), objective response rate (ORR), rate of early tumor shrinkage (ETS), and safety. We hypothesized a threshold 6-month PFS rate of 30% and an expected 6-month PFS rate of 45%. Treatment was considered effective if the lower limit of the 90% confidence interval (CI) of the 6-month PFS rate was >0.30. Ninety-two patients were enrolled in the study. The primary tumor was located on the left side in 86 (95.6%) patients. Twenty (22.0%) patients had received triplet plus cetuximab as previous therapy. Six-month PFS rate was 58.2% (90% CI 49.3% to 66.2%) with a median PFS of 7.0 months (95% CI 5.7-7.6 months). Median OS was 23.6 months (95% CI 16.5-26.3 months). The ORR and ETS rate were 10.7% and 16.9%, respectively, in 83 patients with measurable lesions. The 6-month PFS rate was comparable between patients previously treated with doublet and triplet regimens; however, median PFS was longer for the doublet regimen (7.4 versus 6.4 months, P= 0.036). Our study demonstrated prospectively that RAM plus FOLFIRI is an effective second-line treatment after anti-EGFR antibody-containing first-line therapy in RAS wild-type and left-sided mCRC. Furthermore, the results were similar for patients who were previously treated with triplet regimen.

Factors associated with outcomes of second-line treatment for EGFR-mutant non-small-cell lung cancer patients after progression on first- or second-generation EGFR-tyrosine kinase inhibitor treatment.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutant non-small-cell lung cancer (NSCLC) patients. However, factors associated with outcomes after progression on first-line therapy are seldom investigated. From January 2016 to December 2020, we enrolled 242 EGFR-mutant stage IIIB-IV NSCLC patients who progressed on first- or second-generation EGFR-TKI treatments, and 206 of them receive second-line treatments after disease progression. The factors that predict the survival outcomes of different second-line treatments after disease progression were evaluated. Clinical and demographic characteristics, including metastatic sites, neutrophil-to-lymphocyte ratio (NLR) at first-line progression, and second-line treatment regimens, and whether re-biopsied after disease progression or not, were reviewed for outcome analysis. The univariate analysis showed that the PFS was shorted in male patients (p =0.049), patients with ECOG performance state ≥ 2 (p =0.014), former smokers (p =0.003), patients with brain metastasis (p =0.04), second-line chemotherapy or EGFR-TKIs other than osimertinib (p =0.002), and NLR ≥5.0 (p=0.024). In addition, second-line osimertinib was associated with longer OS compared to chemotherapy and other EGFR-TKI treatment (p =0.001). In the multivariate analysis, only second-line osimertinib was an independent predictor of PFS (p =0.023). Re-biopsy after first-line treatment was associated with a trend of better OS. Patients with NLR ≥5.0 at disease progression had shorter OS than patients with NLR <5.0 (p = 0.008). The benefits of osimertinib necessitate that aggressive re-biopsy after progression on first- or second-generation EGFR-TKI treatment is merited for appropriate second-line treatments to provide better outcomes for these patients.

Chinese expert consensus on the diagnosis and treatment of thymic epithelial tumors

Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first- and second-line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow-up of TETs.