Third-line Treatment Research Articles

Sustained Remission in an Elderly Patient with Acute Myeloid Leukemia Following Gilteritinib Treatment as Third-Line Salvage Therapy

Limited data are available on the effectiveness of gilteritinib as a third-line salvage therapy in patients with acute myeloid leukemia (AML). We present an elderly patient who achieved sustained remission following gilteritinib monotherapy as a third-line treatment after failing two prior regimens.

Bispecific antibodies in follicular lymphoma.

Bispecific antibodies, specifically anti-CD20 T-cell engaging constructs, are poised to alter the treatment paradigm of multiple B-cell malignancies, including follicular lymphoma. Two CD20xCD3 bispecific antibodies, mosunetuzumab and epcoritamab, are now approved in the United States for third-line or later treatment of follicular lymphoma. A third agent, odronextamab, remains under review by regulatory agencies. In pivotal phase II trials, these bispecific antibodies demonstrated overall response rates of approximately 80%, with complete response rates of 60-70%, the majority of which have been durable at two years. Important safety signals included risk of infections, neutropenia, and cytokine release syndrome, which occurred in approximately half of patients, but was rarely high grade. Despite similar efficacy and toxicity profiles, key differences exist among agents, primarily relating to treatment duration, route of administration, and prophylactic corticosteroid use. Several ongoing studies are exploring bispecific antibodies in earlier lines of treatment, either as single agents or in combination with other active therapies. This novel class of agents is likely to play a pivotal role in improving outcomes for patients with follicular lymphoma.

Response to furmonertinib in a patient with non-small cell lung cancer harboring HER2 exon 21 insertion mutation: a case report

BackgroundThis is the first case report describing a patient with non-small cell lung cancer (NSCLC) harboring two rare human epidermal growth factor receptor 2 (HER2) exon 21 insertion mutations, who responded to furmonertinib treatment. Furmonertinib maybe one effective and economical treatment for NSCLC patients harboring HER2 mutations with minor side effects.Case descriptionWe present a case report of a 49-year-old female diagnosed with stage IV lung adenocarcinoma who complained of irritating dry cough symptoms followed by chest tightness. Firstly, we describe the patient’s treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient’s fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed. After that, comprehensive genomic profiling revealed two HER2 exon 21 insertion mutations. Subsequently, the patient received targeted therapy with furmonertinib and achieved 11 months of progression-free survival. The patient received pyrrotinib therapy for 2 months after disease progression, but the disease continued to progress. In October 2023, the patient received therapy with furmonertinib again, and a month later, the disease went into partial remission. However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023.ConclusionFurmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials.

Early Biologic Treatment for Inflammatory Bowel Disease

This rapid review updates the evidence for early biologic treatment versus conventional step-up therapy for patients with luminal Crohn disease, fistulizing Crohn disease, or ulcerative colitis. Findings are based on 4 systematic reviews, 2 randomized controlled trials, and 3 updated clinical guidelines. Luminal Crohn Disease Three systematic reviews showed that early biologic treatment, initiated within 36 months of diagnosis, significantly improved clinical remission, mucosal healing, and reduced relapse rates, surgery needs, and disease progression compared to conventional strategies. Two randomized controlled trials found that early infliximab treatment led to better remission rates, quality of life, and safety outcomes compared with conventional treatment for both adults and children with newly diagnosed moderate-to-severe Crohn disease. These results are consistent with previous evidence suggesting that early biologic drugs improve clinical benefits compared with conventional strategies. Clinical guidelines generally recommend biologic drugs as third-line treatment. One guideline targets adults and children with severe, active Crohn disease, and another focuses on children and adolescents with luminal Crohn disease regardless of severity. Of these, 1 guideline recommends first-line biologics for high-risk pediatric patients. Fistulizing Crohn Disease One guideline recommends third-line infliximab for patients with active fistulizing Crohn disease who did not respond, did not tolerate or had a contraindication to conventional therapy. First-line anti–tumour necrosis factor therapy was only recommended for children and adolescents with fistulizing perianal Crohn disease. No evidence was identified for this population. Ulcerative Colitis In 1 systematic review, early biologics were found to be associated with a higher risk of colectomy. However, these findings should be interpreted with caution as they are based on evidence from 3 observational studies. One guideline recommends infliximab as a third-line option for acute severe cases contraindicated to or clinically inappropriate with ciclosporin.

The Management of Patients with Extrapulmonary Sarcoidosis in Rheumatology Clinic

Abstract Background This study aimed to evaluate patients with extrapulmonary and refractory sarcoidosis who were followed up on in our rheumatology clinic for a long follow-up period and to summarise the applications in rheumatology practice. Materials and Methods The study included patients diagnosed with sarcoidosis at our institution between 2010 and 2022. Patientsʼ age, sarcoidosis diagnosis dates, inflammatory rheumatic disease (iRMD) diagnoses, autoimmune markers, and imaging findings were all evaluated. Estimates were made for cases of glucocorticoid (GC) use and cumulative and mean daily GC exposures. Results 90 patients with sarcoidosis, 79 (87.8) female and 11 (12.2) male, whose mean age was 56.4±12.4 years, were included. Since 48 (53.3%) of the patients required at least one additional treatment in addition to CS, they were classified as having refractory sarcoidosis and followed up accordingly. While 43 (89%) of the patients received second-line sarcoidosis treatment, it was found that 5 patients were switched to third-line sarcoidosis treatment (p<0.001). Comorbidity distributions of refractory and nonrefractory patients were similar. It was determined that 9 (10%) patients had a history of osteoporotic fracture. Conclusions In conclusion, it appears critical to develop a detailed patient management plan and a multidisciplinary approach in the early stages of extrapulmonary sarcoidosis management. There is currently no detailed algorithm covering refractory disease definition and treatment practice differences.

Clinical Outcome Patterns of Use of Radium-223 in Patients with Metastatic Castration-Resistant Prostate Cancer

Introduction: Radium-223 dichloride (radium-223) is a bone-targeting radioisotope therapy that aids in the survival of patients with metastatic castration-resistant prostate cancer (mCRPC) to bones. This study aimed to describe the clinical characteristics and outcomes of patients with mCRPC treated with radium-223 in a real-world setting. Methods: This was a retrospective study of patients with mCRPC treated with radium-223 between 2016 and 2020 at the London Health Sciences Centre in London, Canada. The baseline characteristics between the patients receiving 1–3 and 4–6 treatment cycles were compared using a two-sample t-test and Chi-square test. ANOVA was used to determine if there was a difference in each diagnostic variable per treatment cycle. Kaplan–Meier curves were generated to estimate progression-free survival (PFS) and overall survival in the patients treated with different numbers of cycles. Results: Fifty eligible patients were identified. The median age was 71 years (IQR: 66–76). Most patients (62%) received radium-223 beyond the third-line treatment. The mean number of radium-223 treatments was four. While 60% of the patients received 4–6 injections, 40% received 1–3 injections. Fifty-eight percent (58%) of the patients demonstrated a clinical benefit, with the remainder expressing either disease progression (28%) or stable disease (10%). The patients treated with 4–6 cycles had a delay to disease progression compared to those given 1–3 cycles of radium-223 (F5,35 = 10.52, p < 0.001). A higher alkaline phosphatase level prior to treatment was associated with a longer PFS (z33 = 2.362, p = 0.018). Treatment-related hospitalization for skeletal-related events was noted in 8% of the patients, and 14% required treatment discontinuation due to hematologic toxicity. Conclusions: This study confirms the safety of radium-223 in patients with mCRPC in a real-world setting. The radium-223 treatment was associated with a clinical benefit in the majority of the patients, particularly in those with higher pre-treatment serum alkaline phosphatase levels. Further studies to identify the predictive biomarkers are warranted to better guide the contemporary use of radium-223.

Efficacy and safety of anlotinib combined with S‑1 as a third‑ or later‑line treatment for advanced non‑small cell lung cancer in China: A systematic review and meta‑analysis.

Anlotinib is presently used as a third-line treatment for non-small cell lung cancer. However, it is not yet reported whether combining anlotinib with S-1 as a third- or later-line treatment offers superior outcomes compared with anlotinib alone. The present meta-analysis aimed to address this question by systematically searching the PubMed, Embase, Web of Science, Cochrane Library, CMB and China National Knowledge Infrastructure databases for eligible studies published from the establishment of the database to January 10, 2024. Primary outcomes of interest included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and the incidence of adverse effects, which were presented as hazard ratios and 95% CIs. The present analysis included 5 retrospective studies with a total of 317 patients and compared the outcomes of patients treated with a combination of anlotinib and S-1 (experimental group) compared with anlotinib alone (control group). The combination treatment significantly improved PFS, OS, ORR and DCR in the experimental group compared with the control group. Bone marrow suppression and fatigue were significantly higher in the experimental group compared with the control group. However, incidences of hypertension, proteinuria, gastrointestinal adverse reactions, hepatic and renal insufficiency and functional hand-foot syndrome were higher in the control group compared with the experimental group, but there was no statistical significance. In summary, combining anlotinib with S-1 may be more effective compared with anlotinib alone for treating advanced non-small cell lung cancer. Despite the higher incidence of adverse reactions with the combination therapy, these reactions could be considered manageable and controllable.

SHR-8068 combined with adebrelimab and bevacizumab in the treatment of refractory advanced colorectal cancer: study protocol for a single-arm, phase Ib/II study.

The third-line treatment for refractory colorectal cancer (CRC) has limited efficacy. This study aimed to evaluate the safety and efficacy of SHR-8068 (an anti-CTLA-4 antibody), combined with adebrelimab (an anti-PD-L1 antibody), and bevacizumab in refractory non-microsatellite instability-high (MSI-H) or proficient mismatch repair (pMMR) CRC. This study is a prospective, open-label, single-center phase Ib/II clinical trial. Patients with pathologically confirmed pMMR/non-MSI-H metastatic colorectal adenocarcinoma who have failed ≥2 lines prior standard systemic treatments will be enrolled (n=36). The Ib phase will evaluate two dosing regimens of SHR-8068 in combination therapy (n=9 each dosage): SHR-8068 (1 mg per kilogram, every six weeks, intravenously) or SHR-8068 (4 mg per kilogram, every twelve weeks, intravenously) combined with adebrelimab (1200 mg, every three weeks, intravenously) and bevacizumab (7.5 mg per kilogram, every three weeks, intravenously). The efficacy and adverse events (AEs) of these regimens will be assessed to determine the recommended phase II dose (RP2D) of SHR-8068. Those of RP2D group from the phase Ib will be included in the phase II. The study will go to include 18 additional patients according to the one-sample log-rank test design in the phase II. The primary endpoint of the Ib phase is safety, with secondary endpoints including the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and quality of life (QOL). The primary endpoint for phase II was PFS, with secondary endpoints including ORR, OS, DCR, safety, and QOL. Identifying biomarkers to predict the efficacy of this regimen is the exploratory study endpoint. This proof-of-concept study would provide safety and efficacy signals of this novel combination treatment for the MSS CRCs in the late-line setting. And it may offer new insights on the clinical application of dual immunotherapy combined with anti-angiogenic therapy in the MSS CRC.

Efficacy of antidepressants in the treatment of chronic nonspecific low back pain: a systematic review and meta-analysis.

Aim: This study reassesses the efficacy and safety of antidepressants in treating nonspecific chronic low back pain (NCLBP).Materials & methods: A systematic review was conducted following PRISMA guidelines, including randomized clinical trials (RCTs) from PubMed, Embase, Scopus, LILACS, SciELO and Cochrane CENTRAL, published through August 2024. Studies compared antidepressants with placebo or active comparators. The primary outcomes were pain relief and quality of life. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42023307516.Results: Nine RCTs involving 1758 patients were analyzed. The antidepressants examined included duloxetine, escitalopram, bupropion, amitriptyline, imipramine and desipramine. Duloxetine 60mg significantly reduced pain (MD=-0.57; 95% CI=-0.78 to -0.36) and improved quality of life compared with placebo, with side effects that were generally tolerable. Notably, higher doses of duloxetine (120mg) were associated with an increase in adverse events. However, other antidepressants like amitriptyline and escitalopram demonstrated only modest or inconsistent effects.Conclusion: Duloxetine at 60mg provides consistent pain relief and improves the quality of life in NCLBP, but higher doses increase adverse events. Escitalopram might offer modest benefits but should be considered a third-line treatment. Other antidepressants, such as amitriptyline, bupropion, imipramine and desipramine, have limited evidence supporting their efficacy and are associated with adverse effects.

Bi-weekly irinotecan is an effective and convenient regimen in the treatment of relapsed or refractory small cell lung cancer

BackgroundDespite initial dramatic responses, metastatic small cell lung cancer (SCLC) invariably recurs. Irinotecan is one of the active agents for patients with recurrent SCLC. In the second line, weekly or three-weekly irinotecan regimens have been adopted, however, the optimal dose and schedule is not defined. In our institution, we use a bi-weekly regimen of irinotecan. In this study, we aimed to investigate the safety and efficacy of the bi-weekly irinotecan in the second- or third-line treatment of SCLC patients.MethodsThe study population consisted of advanced stage SCLC patients who were followed at Hacettepe University Cancer Institute between January 2007 and March 2021 and received salvage irinotecan 180 mg/m2 every two weeks, following progression after platinum-etoposide treatment.ResultsOne hundred patients were included. At diagnosis, nineteen patients (19%) had limited stage and 81 patients (81%) had extensive stage SCLC. Objective response rates (ORR) were 44.6% and 46.2% for patients who received irinotecan treatment in second line, and in third line, respectively. Seventeen percent of all the patients had grade 3 and above adverse events during irinotecan treatment. In our study, 45.8% of patients were able to complete at least 6 cycles of irinotecan treatment and 69.8% were able to receive at least 3 cycles of irinotecan treatment without any dose interruption or reduction.ConclusionsIrinotecan 180 mg/m2 every two weeks appears to be safe and effective in the 2nd- and 3rd-line treatment of advanced stage SCLC. Bi-weekly administration allows G-CSF prophylaxis in between doses, leading to an uninterrupted administration.

Systemic Therapy Options for Peritoneal Mesothelioma.

Peritoneal mesothelioma is an uncommon malignancy affecting approximately 300 new patients annually in the United States. Due to its low incidence, prospective clinical trials specific to this disease are scant. Recommendations regarding systemic therapy are mostly extrapolated from clinical trials conducted among patients with pleural mesothelioma. At present, the recommended first-line systemic treatment options may include immunotherapy with nivolumab plus ipilimumab or chemotherapy with pemetrexed plus either cisplatin or carboplatin. For second-line treatment, the other previously unchosen first-line option can be used. Off-label bevacizumab may be considered in combination with chemotherapy among carefully selected patients. The benefit of third-line treatment or beyond is less clear. Nonetheless, a number of single-agent regimens show modest activity. Anecdotal reports of children or young adults with peritoneal mesothelioma harboring ALK rearrangement have suggested the efficacy of ALK inhibitors for this rare population. In summary, there is a growing number of systemic therapy options for peritoneal mesothelioma. To gain a better insight into this disease, future prospective trials in mesothelioma should include more patients with peritoneal mesothelioma.

Cisplatin-Containing Combinations Associate with Survival in Women from Appalachian Kentucky with Metastatic, Persistent, or Recurrent Uterine Cervix Cancer.

Background: Prior preclinical studies showed promising antitumor activity and an acceptable safety profile associated with radiopharmaceuticals for patients with metastatic, persistent, or recurrent uterine cervix cancers. Whether the addition of a radiopharmaceutical to chemotherapy would significantly increase progression-free survival in such patients is untested. Our retrospective study sought to associate the line of treatment and progression-free survival as benchmarks for next-generation radiopharmaceutical development. Methods: We grouped metastatic, persistent, or recurrent uterine cervix cancer patients not amenable to curable surgery or radiotherapy between 2002 and 2023 by the line of doublet, triplet, and quadruplet chemotherapy or another intervention. After the first-line treatment, patients were monitored for radiographic progression every three months for up to three years. The primary endpoints were the first and any second or third progression-free survival intervals. Results: A total of 127 patients contributed demographic, tumor, line of treatment, and outcome data with a median follow-up of 18 months (25-75% interquartile range: 9 to 37 months). After the first-line treatment, 113 patients had local or distant progression or died from any cause, most often death from the disease (67%). Median progression-free survivals were 5.5 months (95% confidence interval: 4.8-6.0 months), 5.3 months (95% confidence interval: 4.5-6.3 months), and 3.0 months (95% confidence interval: 2.1-3.7 months) for the first-, second-, and third-line treatments, respectively. For a first-line cisplatin-containing regimen, the median progression-free survival was 6.5 months (95% confidence interval: 5.5-7.7 months). Conclusions: This study highlights the limited efficacy of current treatments for metastatic, persistent, or recurrent uterine cancer patients. A five-month progression-free survival might serve as a benchmark for the development of novel therapies in clinical efficacy trials, such as radiopharmaceuticals.

Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial

There is an unmet need for second-line and third-line treatments that are effective and tolerable for advanced or metastatic non-small-cell lung cancer (NSCLC) with no driver mutations. In this phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial, we enrolled patients from 58 medical centres in Australia, China, and the USA. Eligible patients were adults with epidermal growth factor receptor (EGFR) wild-type NSCLC who had progressed after first-line platinum-based therapy. Patients were randomly assigned (1:1) using an independent stratified randomisation schedule with a block size of four to receive intravenous docetaxel 75 mg/m2 on day 1 and either plinabulin (30 mg/m2) or placebo on days 1 and 8 in 21-day cycles until progression, unacceptable toxic effects, withdrawal, or death. The primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Safety was analysed in all patients who had received at least one dose of study drug or placebo. This trial is registered with ClinicalTrials.gov (NCT02504489) and is now closed. Between Nov 30, 2015, and Jan 6, 2021, 919 patients were screened for inclusion. 360 patients were excluded, and 559 were enrolled and randomly assigned to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). 406 (73%) of 559 patients were male, 153 (27%) were female, and 488 (87%) were Asian. Median OS was 10·5 months (95% CI 9·34-11·87) in the plinabulin group compared with 9·4 months (8·38-10·68) in the control group (stratified HR 0·82, 95% CI 0·68-0·99; p=0·0399). Mean OS was 15·08 months (13·42-16·74) in the plinabulin group compared with 12·77 months (11·45-14·10) in the placebo group using restricted mean survival time analysis (difference 2·31 months, 95% CI 0·18-4·44; p=0·0332). Treatment-emergent adverse events occurred in 273 (>99%) of 274 patients in the plinabulin group and 276 (99%) of 278 patients in the control group. Grade 3 or 4 gastrointestinal disorders occurred more frequently in the plinabulin group than in the placebo group, with the most frequent being diarrhoea (24 [9%] of 274 patients vs three [1%] of 278) and vomiting (six [2%] vs one [<1%]), as did transient grade 3 hypertension (50 [18%] vs eight [3%]). Treatment-emergent death was reported in 12 patients (4%) in the plinabulin group and ten patients (4%) in the placebo group. Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population. BeyondSpring Pharmaceuticals.

974P Surufatinib combined with anti-PD-1/PD-L1 antibody in the second-line or monotherapy in third-line treatment of advanced hepatocellular carcinoma: A single-arm, open-label, multi-center phase II study

974P Surufatinib combined with anti-PD-1/PD-L1 antibody in the second-line or monotherapy in third-line treatment of advanced hepatocellular carcinoma: A single-arm, open-label, multi-center phase II study

Tazemetostat for relapsed/refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan: 3-year follow-up for a phase II study

Previously, we reported the efficacy and safety of tazemetostat in Japanese patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) harboring the EZH2 mutation in a multicenter, open-label, phase II study. Here, we present a follow-up analysis of tazemetostat at a long-term median follow-up of 35.0 months. Twenty patients were enrolled: 17 in the FL cohort and three in the DLBCL cohort. In the FL cohort, the objective response rate was 70.6%, consistent with the primary analysis, and the median progression-free survival (PFS) was not reached. The 24-month and 36-month PFS rates were 72.1% (95% confidence interval [CI] 41.5%–88.6%) and 64.1% (95% CI 33.7%–83.4%), respectively. The median duration of treatment was 30.2 months. After the primary analysis at a median follow-up of 12.9 months, grade 1–2 urinary tract infection, peripheral motor neuropathy, and hypogammaglobulinemia newly emerged, but the incidence of adverse events (AEs) did not increase notably during this follow-up period. No unexpected grade ≥ 3 treatment-related AEs were reported. Long-term oral monotherapy with tazemetostat showed favorable efficacy and safety profiles, indicating that it may be a useful third-line or later treatment option for patients with relapsed/refractory FL harboring the EZH2 mutation. Trial registration: ClinicalTrials.gov: NCT03456726.

Real-world treatment patterns, resource utilization and costs in biliary tract cancers in the USA.

Aim: To evaluate real-world treatment patterns, survival and healthcare-resource utilization in US patients with advanced biliary tract cancers (BTC) receiving systemic therapy.Patients & methods: This study used claims data from the Healthcare Integrated Research Database (HIRD®) linked to clinical data from the Cancer Care Quality Program (January 1, 2015-September 30, 2020).Results: Of 413 patients, 84.5% received gemcitabine-based first-line (1L) treatment, 46% received second-line treatment, and 16.5% received third-line (3L) treatment. All-cause mortality was 53% and approximately 70% of patients had ≥1 inpatient visit. The total mean per-patient-per-month all-cause costs were $19,589 for 1L and $33,534 for 3L treatment.Conclusion: Results showed poor survival, significant resource use and high costs as treatment line progresses for patients with advanced BTC.

Clinical outcomes for immune checkpoint inhibitors plus chemotherapy in non-small-cell lung cancer patients with uncommon driver gene alterations

BackgroundLimited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC.MethodsWe retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024.ResultsOf the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively.ConclusionICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population.

Management of Guttate Psoriasis: A Systematic Review.

Guttate psoriasis (GP) is a variant of psoriasis characterized by scattered "drop-like" papules and plaques, accounting for up to a quarter of psoriasis cases. Although GP can clear within 3 to 4 months, up to 39% of cases may progress to chronic plaque psoriasis. Currently, there is a paucity of literature investigating the efficacy of different treatment modalities. This systematic review aims to synthesize all available data on GP treatment efficacy. A literature search was conducted using Medline, Embase, Web of Science, and CINAHL with no date limits. A total of 75 studies satisfied eligibility criteria and were analyzed. Most studies were case reports, series, or retrospective studies. Only 5 randomized controlled trials (RCTs) were identified. For topical treatments, corticosteroids and calcipotriol creams had the most evidence for efficacy. Four categories of systemic therapies were identified: traditional immunosuppressants, antibiotics, retinoids, and biologics. Evidence regarding antibiotic therapy suggests minimal connection between underlying infection resolution and GP lesion remission. Phototherapy had the most robust evidence, with narrowband ultraviolet B (UVB) being the most effective. Our findings are limited by high heterogeneity in study design and high risk of bias. Based on our review, we propose the following treatment algorithm. As first-line therapy, we recommend topical corticosteroids and calcipotriol cream, in combination with phototherapy. As supportive therapy, we recommend antibiotics if applicable. For second-line therapy, we recommend methotrexate or cyclosporine. For severe and refractory GP, biologics can be used as third-line treatment. RCTs are needed to provide higher quality evidence to create standardized treatment recommendations.

Current status of palliative care for patients with unresectable metastatic colorectal cancer in China: a questionnaire-based survey

Objective: To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China. Methods: From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis. Results: A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0-1. After receiving third- and fourth-line treatment, 50%-60% of patients maintained a good quality of life and 40%-50% of them maintained ECOG performance scores of 0-1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer. Conclusions: This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.

Thiamylal serum concentration for refractory convulsive status epilepticus while associated decreased concentrations of concomitant antiepileptics: a case report

BackgroundTreating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs.Case presentationA 72-year-old healthy man developed RSE. Despite the administration of various AEDs, his seizures were not resolved. Thiamylal was then administered at an initial bolus dose of 2.1 mg/kg, followed by a continuous infusion of 4.2–5.2 mg/kg/h. The initial thiamylal concentration was observed at 7.8 μg/mL, increasing to 35.2 μg/mL before decreasing after dose reduction and cessation. Concurrently, the concentration of concomitant carbamazepine decreased from 5.59 μg/mL to 2.1 μg/mL and recovered as thiamylal concentration decreased. Lesser impacts were noted for other AEDs.ConclusionsThis case report underscored the efficacy of thiamylal in treating RSE. However, it also highlighted the need for clinicians to closely monitor the concentrations of concurrent AEDs, especially carbamazepine, during thiamylal therapy.