Best Supportive Care In Patients Research Articles

Best supportive care in advanced pancreas cancer: a systematic review to define a patient-care bundle.

The majority of patients with pancreatic adenocarcinoma (PDAC) have advanced disease at presentation, preventing treatment with curative intent. Management of these patients is often provided by surgical teams for whom there are a lack of widely accepted strategies for care. The aim of this study was to conduct a systematic review to identify key issues in patients with advanced PDAC and integrate the evidence to form a care bundle checklist for use in surgical clinics. A systematic review of the literature was performed regarding best supportive care for advanced PDAC according to the PRISMA guidelines. Interventions pertaining to supportive care were included whilst preventative and curative treatments were excluded. A narrative review was planned. Forty-four studies were assessed and four themes were developed: (i) Pain is an undertreated symptom, requiring escalating analgesics and sometimes invasive modalities. (ii) Health-related quality of life necessitates optimisation by involving family, carers and multi-disciplinary teams. (iii) Malnutrition and weight loss can be mitigated with early assessment, replacement therapies and resistance exercise. (iv) Biliary and duodenal obstruction can often be relieved by endoscopic/radiological interventions with surgery rarely required. This is the first systematic review to evaluate the different types of interventions utilized during best supportive care in patients with advanced PDAC. It provides a comprehensive care bundle for surgeons that informs management of the common issues experienced by patients within a multidisciplinary environment.

A cautionary tale: an evaluation of the performance of treatment switching adjustment methods in a real world case study

BackgroundTreatment switching in randomised controlled trials (RCTs) is a problem for health technology assessment when substantial proportions of patients switch onto effective treatments that would not be available in standard clinical practice. Often statistical methods are used to adjust for switching: these can be applied in different ways, and performance has been assessed in simulation studies, but not in real-world case studies. We assessed the performance of adjustment methods described in National Institute for Health and Care Excellence Decision Support Unit Technical Support Document 16, applying them to an RCT comparing panitumumab to best supportive care (BSC) in colorectal cancer, in which 76% of patients randomised to BSC switched onto panitumumab. The RCT resulted in intention-to-treat hazard ratios (HR) for overall survival (OS) of 1.00 (95% confidence interval [CI] 0.82–1.22) for all patients, and 0.99 (95% CI 0.75–1.29) for patients with wild-type KRAS (Kirsten rat sarcoma virus).MethodsWe tested several applications of inverse probability of censoring weights (IPCW), rank preserving structural failure time models (RPSFTM) and simple and complex two-stage estimation (TSE) to estimate treatment effects that would have been observed if BSC patients had not switched onto panitumumab. To assess the performance of these analyses we ascertained the true effectiveness of panitumumab based on: (i) subsequent RCTs of panitumumab that disallowed treatment switching; (ii) studies of cetuximab that disallowed treatment switching, (iii) analyses demonstrating that only patients with wild-type KRAS benefit from panitumumab. These sources suggest the true OS HR for panitumumab is 0.76–0.77 (95% CI 0.60–0.98) for all patients, and 0.55–0.73 (95% CI 0.41–0.93) for patients with wild-type KRAS.ResultsSome applications of IPCW and TSE provided treatment effect estimates that closely matched the point-estimates and CIs of the expected truths. However, other applications produced estimates towards the boundaries of the expected truths, with some TSE applications producing estimates that lay outside the expected true confidence intervals. The RPSFTM performed relatively poorly, with all applications providing treatment effect estimates close to 1, often with extremely wide confidence intervals.ConclusionsAdjustment analyses may provide unreliable results. How each method is applied must be scrutinised to assess reliability.

Cost-Effectiveness of Oral Nirmatrelvir/Ritonavir in Patients at High Risk for Progression to Severe COVID-19 in the United States

ObjectivesNirmatrelvir/ritonavir (NMV/r) is an orally administered antiviral indicated for the outpatient treatment of patients with mild-to-moderate COVID-19 at high risk for disease progression to severe illness. We estimated the cost-effectiveness of NMV/r versus best supportive care for patients with mild-to-moderate COVID-19 at high risk for progression to severe illness from a US health sector perspective. MethodsA cost-effectiveness model was developed using a short-term decision-tree (1 year) followed by a lifetime 2-state Markov model (alive and dead). The short-term decision-tree captured costs and outcomes associated with the primary infection and healthcare utilization; survivors of the short-term decision-tree were followed until death assuming US quality-adjusted life years (QALYs), adjusted in the short-term for survivors of mechanical ventilation. Baseline rate of hospitalization and NMV/r effectiveness were taken from an Omicron-era US real-world study. Remaining inputs were informed by previous COVID-19 studies and publicly available US sources. Sensitivity analyses were conducted for all model inputs to test the robustness of model results. ResultsNMV/r was found to decrease COVID-19 related hospitalizations (−0.027 per infected case) increase QALYs (+0.030), decrease hospitalization costs (−$1110), and increase total treatment cost (+$271), resulting in an incremental cost-effectiveness ratio of $8931/QALY. Results were most sensitive to baseline risk of hospitalization and NMV/r treatment effectiveness parameters. The probabilistic analysis indicated that NMV/r has a >99% probability of being cost-effective at a $100 000 willingness-to-pay threshold. ConclusionsNMV/r is cost-effective vs best supportive care for patients at high risk for severe COVID-19 from a US health sector perspective.

Treatment Outcomes in Unfit Patients with Newly Acute Myeloid Leukemia According to IDH1 Mutational Status: Real World Evidence from the Pethema Epidemiologic Registry

Background: Current treatment of unfit acute myeloid leukemia (AML) patients include hypomethylating agents (HMA) with or without venetoclax, low-dose cytarabine (LDAC), and supportive care only. Recently, the combination of azacytidine with ivosidenib, an IDH1 inhibitor, has showed a significant improvement in survival in unfit patients with IDH1 mutated (IDH1mut) AML compared to azacytidine plus placebo. Real world studies analyzing outcomes of IDH1mut AML patients are scarce. Aims: This study aims to assess retrospectively the characteristics, therapeutic approaches, and outcomes of unfit patients with AML in an unselected population reported to the multicentric PETHEMA registry according to IDH mutational status. We present here a first interim analysis, as the study is aimed to enroll 3500 patients. Methods: AML unfit patients reported to PETHEMA registry between January 2015 and June 2022 were included in the study, regardless of their therapeutic approach. IDH1 mutational status was analyzed with next generation sequencing (NGS) and polymerase chain reaction (PCR) technics performed in central labs from PETHEMA group, as well as locally as per standard practice. All clinical records were reviewed from diagnosis to death/last follow-up and data were analyzed with R statistical software. Results: From 9398 patients reported to the PETHEMA registry between 2015 and 2022, 4533 patients had information on IDH1 mutational status. Of them, 2096 patients were unfit for intensive chemotherapy, and therapeutic approach was available in 1255 patients who were evaluable for this interim report. Median age was 75 years, 716 (57%) were male, 312 (35%) had adverse cytogenetic-risk. Overall, 141 (11%) had IDH1mut [106 (12.4%) by NGS and 77 (9.9%) by PCR only] and 1114 (89%) had no IDH1 mutation (IDH1wt). There were differences between IDH1mut vs IDH1wt cohorts regarding white blood cells (WBC) count (P=0.003), platelets count (P=0.002), bone marrow blasts percentage (P<0.001), MRC cytogenetic risk (P=0.02) and NPM1 mutational status (P<0.001). More detailed information is shown in Table 1. Regarding treatments, 176 (15%) patients received only best supportive care (BSC), 293 (23%) were included in non-intensive clinical trials, 433 (34%) received HMAs, 281 (22%) LDAC schedules and 62 (5%) venetoclax plus HMA or LDAC (VEN). From 818 patients with available response, 261 (32%) achieved complete remission (CR) or CR with incomplete recovery (CRi), 105 (13%) partial remission, 305 (37%) were resistant and 147 (18%) died before being assessed. No statistical differences were observed between IDH1mut and IDH1wt groups (P=0.18). Median overall survival (OS) was 5.9 months (CI95, 5.3-6.7), with no differences in IDH1mut and IDH1wt cohorts [median 7.7 months (CI95, 5.9-11.2) vs 5.6 (CI95, 5-6.4)], with a 2y-OS of 15% (9.7-24.5) vs 15% (12.9-18.2), respectively (P=0.24). Median OS was 7.9 (CI95, 6.8-9.3) in patients receiving active treatment. Patients receiving VEN schedules had a median OS of 11.1 months (CI95, 9.4-14.1) vs 10.5 (CI95, 8.2-13.0) in patients included in clinical trials vs 8.3 (CI95, 6.7-10.0) in those receiving HMA vs 5.5 (CI95, 4.5-6.8) treated with LDAC-based schemes vs 0.4 (CI95, 0.3-0.7) in BSC patients (P<0.001). Figure 1 shows OS according to therapeutic approach in all patients. According to the therapeutic approach, IDH1mut patients included in clinical trials had a median OS of 16.8 (CI95, 6.0-NA) vs 10.6 months (CI95, 9.9-NA) in patients receiving VEN schedules vs 9.0 (CI95, 6.5-14.5) in those receiving HMA vs 7.0 (CI95, 5.5-12.7) with LDAC-based vs 0.6 (CI95, 0.2-3.7) in BSC patients (P<0.001). Conclusion: We show a prevalence of 11% of IDH1 mutation among patients considered unfit to receive intensive chemotherapy. Although there were differences between IHD1mut and IDH1wt subgroups in some variables with demonstrated prognostic impact, no significant differences were observed in response to treatment or OS. This study was partially supported by Servier.

Survival after living donor liver transplantation versus best supportive care in patients with end-stage liver disease with various MELD-Na scores: retrospective cohort study.

Survival after living donor liver transplantation versus best supportive care in patients with end-stage liver disease with various MELD-Na scores: retrospective cohort study.

THU-134 - Feasibility of systemic anti-cancer therapy as an alternative to best supportive care in patients with advanced HCC and Child-Pugh B liver dysfunction

THU-134 - Feasibility of systemic anti-cancer therapy as an alternative to best supportive care in patients with advanced HCC and Child-Pugh B liver dysfunction

Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non-Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy.

To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7.1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P < .001), as was median survival (7.0 v 4.6 months; log-rank test, P = .047). The difference was more significant for docetaxel 75 mg/m2 patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P = .010; 1-year survival, 37% v 11%; χ2 test, P = .003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m2, three of whom died, and in one patient treated with docetaxel 75 mg/m2. Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m2, the benefits of docetaxel therapy outweigh the risks.

Efficacy of avelumab in the treatment of oncourological malignances. Results of registration studies and own experience

Background. In the JAVELIN Bladder 100 trial, 1st line maintenance with avelumab in combination with best supportive care significantly increased (9.2 months) overall survival compared to best supportive care in patients with locally advanced or metastatic urothelial cancer without progression after 1st line platinum-based chemotherapy: 29.7 months versus 20.5 months, respectively. Trial results led to inclusion of avelumab into the international guidelines as a standard of care with the highest level of evidence. Combined therapy with avelumab + axitinib in patients with previously untreated metastatic renal cell carcinoma showed higher progression-free survival and objective response rate compared to sunitinib in all IMDC (International Metastatic Renal Cancer Database Consortium) groups. Avelumab + axitinib is one of the immuno-oncology combinations with proven effectiveness for progression-free survival and objective response rate.Aim. To evaluate the effectiveness of avelumab in treatment of oncological urological diseases in routine clinical practice. Materials and methods. At the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology - branch of the National Medical Research Radiology Center, 12 patients with locally advanced inoperable and metastatic urothelial cancer without progression after 1st line platinum-based chemotherapy in combination with gemcitabine received maintenance avelumab therapy. Median follow-up was 10 months. Primary endpoints were overall survival from the start of avelumab maintenance therapy and safety.Combined therapy with avelumab + axitinib was administered in 18 patients with metastatic renal cell carcinoma. Median follow-up was 9 (3-16) months. Overall survival, progression-free survival, response rate and safety in the overall population and according to IMDC groups were evaluated.Results. At data cut-off (March 2023) with median follow-up of 10 months, overall survival was 100 %, progression-free survival was 66.7 % (among patients who received more than 3 infusions - 100 %). Progression-free survival was higher in patients with tumors of the lower urinary tract compared to upper (72.5 % versus 60 %), complete response to induction platinum-based chemotherapy compared to partial response and stable disease (100 % versus 66.7 %) and presence of metastases in the lymph nodes only compared to visceral and bone metastases (100 % versus 66.7 %). Adverse events were observed in 4 (66.7 %) patients.Among 18 patients who received avelumab + axitinib, complete response was observed in 2 (11.1 %) patients, partial response in 6 (33.3 %) patients, stable disease in 9 (50 %) patients, disease progression in 1 (5.6 %) patient. Response to therapy was observed in patients of all prognosis groups; for large (&gt;5 cm) metastases in the lungs, soft tissues, lymph nodes and bones response was observed 3 months after treatment start. Overall survival for this follow-up duration was 100 %, progression-free survival was 96.4 ± 11.2 %. Adverse events were observed in 8 (44.4 %) patients, and in 6 (75 %) of them they were grade I—II and did not require infusion regimen correction or axitinib dose reduction.Conclusion. Avelumab maintenance therapy in the 1st line is the standard of care for patients with locally advanced and metastatic urothelial cancer without disease progression during 1st line platinum-based chemotherapy. Maintenance therapy allows to achieve better overall survival and progression-free survival irrespective of the choice of platinum regimen (cisplatin or carboplatin), response to platinum-based chemotherapy, number of chemotherapy cycles, tumor localization and advancement.Experience of the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology confirms results of the JAVELIN Bladder 100 trial on the effectiveness of avelumab maintenance therapy in routine clinical practice. Combination drug therapy with avelumab and axitinib in patients with metastatic renal cell carcinoma is an effective and safe treatment method which allows to achieve fast objective response and has good tolerability in patients irrespective of IMDC group or metastasis location. Effectiveness and favorable safety profile of avelumab + axitinib combination were proven in the context of routine clinical practice.

Epidemiological and Therapeutic Analyses in Lung Cancer Patients Over 80 Years Old in the Hokushin Region: A Retrospective Hospital Administrative Database Study

ObjectiveThis study was performed to validate the epidemiology, initial treatment, and clinical practice in lung cancer patients < 80 and ≥ 80 years in Hokushin region, Japan. MethodsWe retrospectively surveyed data of 5481 newly diagnosed and registered lung cancer patients (4311 [78.7%] < 80 years; 1170 [21.3%] ≥ 80 years ) in 22 principal hospitals in Hokushin region linked with health insurance claims data between 2016 and 2017. Stage, initial treatment, and clinical practice were compared between the 2 groups. ResultsThe distributions of clinical stage I/II/III/IV/unknown were 2535/387/654/1371/111 in non-small cell lung cancer (NSCLC) and 37/32/114/237/3 in SCLC. Initial surgery for stage I NSCLC was performed in 90.0% and 60.2% of cases in the < 80 and ≥ 80 years groups, respectively. Rates of treatment with best supportive care (BSC) for stage IV disease were significantly higher in the ≥ 80 than the < 80 years group (NSCLC:58.9% vs. 18.7%; SCLC: 42.3% vs. 6.8%, respectively), regardless of the presence/absence of comorbidities. Propensity score matching showed that age ≥ 80 years itself was significantly related to choice of BSC in patients with lung cancer. The ratio of initial cytotoxic chemotherapy for NSCLC was low (49.9%) but that of biomarker-based therapy including tyrosine kinase inhibitors and immune checkpoint inhibitors (50.0%) was significantly higher in the ≥ 80 than < 80 years group (70.2% vs. 29.8%, respectively). ConclusionThere are several differences in treatment pattern between patients < 80 and ≥ 80 years. Age ≥ 80 years may be related to BSC choice in patients with lung cancer.

Stereotactic ablative radiotherapy or best supportive care in patients with localized pancreatic cancer not receiving chemotherapy and surgery (PANCOSAR): a nationwide multicenter randomized controlled trial according to a TwiCs design

BackgroundSignificant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with ‘best supportive care’. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible.MethodsA nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the ‘Trial within cohorts’ (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with ‘best supportive care’ and ‘best supportive care’ only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR.DiscussionThe PANCOSAR trial studies the added value of SBRT as compared to ‘best supportive care’ in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients.Trial registrationClinical trials, NCT05265663, Registered March 3 2022, Retrospectively registered.

Serum SALL4 as a predictive biomarker for the prognosis of patients with hepatocellular carcinoma who underwent nonsurgical treatment.

To investigate the role of serum spalt like transcription factor 4 (SALL4) in the hepatocellular carcinoma (HCC) patients with nonsurgical treatment. Serum samples were collected from 101 patients with HCC without surgical treatment, then the SALL4 was detected by enzyme linked immunosorbent assay. According to subsequent treatment, patients were divided into 2 groups, best supportive care (BSC) (58 cases) and nonsurgical anticancer treatment (NSAT) (48 cases). Kaplan-Meier survival analysis and Cox multivariate regression analysis were applied to evaluate the relationship between SALL4 and survival time of 2 groups. In BSC group, there was no significant difference of the survival time between 2 groups (SALL4 < 800 ng/mL or SALL4 ≥ 800 ng/mL) (P = .339). In NSAT group, the survival time of patients with low SALL4 concentration was significantly longer than patients with high SALL4 concentration (P = .005). SALL4 have no predictive effect in BSC patients with HCC. But for patients received NSAT, low SALL4 concentration in serum may indicate longer survival.

Suprachoroidal Injection of Triamcinolone Acetonide Injectable Suspension for the Treatment of Macular Edema Associated With Uveitis in the United States: A Cost-Effectiveness Analysis

ObjectivesSuprachoroidal injection of triamcinolone acetonide is the first Food and Drug Administration–approved treatment for macular edema associated with uveitis. A cost-effectiveness analysis was performed comparing this treatment with best supportive care (BSC) for the management of this indication from US Medicare and commercial payer perspectives. MethodsA patient-level simulation was developed per the patient characteristics and changes in best-corrected visual acuity letter scores observed in a phase III study of triamcinolone acetonide (PEACHTREE). The wholesale acquisition cost of triamcinolone acetonide was $1650/injection; suprachoroidal injection cost was assumed at $200/injection. Healthcare costs were informed by a US claims–based analysis. Mortality risk associated with severe vision loss and blindness was modeled by applying a hazard ratio to all-cause mortality rates of the US general population. Health-related quality of life weights, obtained from a regression model fitted to the Visual Function Questionnaire-25 data from PEACHTREE, were applied based on the best-corrected visual acuity scores of both eyes. Costs (2020 US dollar) and benefits were discounted at 3% annually. Incremental cost-effectiveness ratios were estimated over a 10-year horizon. ResultsIn the base-case, the incremental cost-effectiveness ratio comparing triamcinolone acetonide with BSC was $28 479 per quality-adjusted life-year gained. The wholesale acquisition cost for triamcinolone acetonide for suprachoroidal use was ∼68%, ∼56%, and ∼27% below the willingness-to-pay thresholds of $150 000, $100 000, and $50 000 per quality-adjusted life-year gained, respectively. Results were robust in sensitivity and scenario analyses. ConclusionsTriamcinolone acetonide for suprachoroidal use is cost-effective compared with BSC for patients with macular edema associated with uveitis.

The Cost Effectiveness of Axicabtagene Ciloleucel Versus Best Supportive Care in the Treatment of Adult Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL) After Two or More Lines of Systemic Therapy in Canada.

Axicabtagene ciloleucel (axi-cel) received marketing authorisation in Canada for the treatment of relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, and the clinical and economic value of axi-cel to patients and the healthcare system should be examined. The objective of this analysis is to determine, from societal and public healthcare payer perspectives, the cost effectiveness of axi-cel versus best supportive care for patients with relapsed or refractory large B-cell lymphoma in Canada. A pharmacoeconomic model was developed and populated with clinical data derived from the ZUMA-1 and SCHOLAR-1 studies using a propensity score-matched comparison. A partitioned survival mixture-cure modelling approach was taken to characterise the potential curative effect of axi-cel therapy in large B-cell lymphoma. Healthcare resource utilisation and adverse event data were based on results from ZUMA-1, and utility values were derived from ZUMA-1 data supplemented with published literature. Costs (in 2021 Canadian dollars) were taken from publicly available Canadian cost databases and published literature. Benefits and costs were discounted at 1.5% per year, and sensitivity analyses were conducted to assess the robustness of the results. In the base case, axi-cel generated an incremental 6.2 life-years compared to best supportive care, corresponding to 4.6 additional quality-adjusted life-years, and was associated with $606,010 in additional costs. The incremental cost-utility ratio was $132,747 per quality-adjusted life-year gained compared with best supportive care from a societal perspective ($106,392 per quality-adjusted life-year gained from a public healthcare payer perspective). Key drivers of the analysis included progression-free survival and overall survival values for axi-cel. The results of this analysis suggest that axi-cel may be considered a cost-effective allocation of resources compared with best supportive care for the treatment of adult patients with relapsed or refractory large B-cell lymphoma in Canada.

Patient-reported Outcomes from JAVELIN Bladder 100: Avelumab First-line Maintenance Plus Best Supportive Care Versus Best Supportive Care Alone for Advanced Urothelial Carcinoma

BackgroundIn JAVELIN Bladder 100, avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) versus BSC alone in patients with advanced urothelial carcinoma (aUC) without disease progression with first-line platinum-containing chemotherapy. ObjectiveTo evaluate patient-reported outcomes (PROs) with avelumab plus BSC versus BSC alone. Design, setting, and participantsA randomized phase 3 trial (NCT02603432) was conducted in 700 patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line gemcitabine plus cisplatin or carboplatin. PROs were a secondary endpoint. InterventionAvelumab plus BSC (n = 350) or BSC alone (n = 350). Outcome measurements and statistical analysisNational Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQol five-level EQ-5D (EQ-5D-5L) assessments were analyzed using descriptive statistics and mixed-effect models. Time to deterioration (TTD; prespecified definition: a ≥3-point decrease from baseline in the FBlSI-18 disease-related symptoms–physical subscale for two consecutive assessments) was evaluated via Kaplan-Meier analyses. Results and limitationsCompletion rates for scheduled on-treatment PRO assessments were >90% (overall and average per assessment). Results from descriptive analyses and mixed-effect or repeated-measures models of FBlSI-18 and EQ-5D-5L were similar between arms. TTD was also similar, both in the prespecified analysis (hazard ratio 1.26 [95% confidence interval: 0.90, 1.77]) and in the post hoc analyses including off-treatment assessments and different event definitions. Limitations included the open-label design and limited numbers of evaluable patients at later time points. ConclusionsAddition of avelumab first-line maintenance to BSC in patients with aUC that had not progressed with first-line platinum-containing chemotherapy prolonged OS, with a relatively minimal effect on quality of life. Patient summaryIn this trial of people with advanced urothelial carcinoma who had benefited from first-line chemotherapy (ie, had stable disease or reduced tumor size), treatment with avelumab maintenance plus best supportive care (BSC) versus BSC alone improved survival significantly, without compromising quality of life, as reported by the patients themselves.

Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): an open-label, parallel, randomized, phase 2 trial

BackgroundCancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy.MethodsPatients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group).DiscussionThe purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice.Trial registrationThis clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT 04907864) on June 1, 2021.

Effect of systemic therapies or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: The Meet‐Uro 19BEYOND study

BackgroundNivolumab and cabozantinib are currently approved agents in metastatic renal cell carcinoma (mRCC) but there are no data available for patients progressing to both treatments. The aim of this study was to compare active therapeutic options and best supportive care (BSC) after progression to nivolumab and cabozantinib in mRCC.MethodsIn this retrospective study, we selected 50 patients from eight Italian centers. The primary endpoint of the study was the overall survival (OS) of patients on active treatment versus BSC. Secondary endpoints were the progression‐free survival (PFS) and objective response rate (ORR). The efficacy of active therapy was also investigated.ResultsAfter progression to both nivolumab and cabozantinib, 57.1% of patients were given active treatment (mainly everolimus and sorafenib) while 42.9% received BSC. The median OS was 13 months (95% CI: 4‐NR) in actively treated patients and 3 months (95% CI: 2–4) in BSC patients (p = 0.001). Patients treated with sorafenib had better disease control than those treated with everolimus (stable disease: 71.4% vs. 16.7%, progression disease: 14.3% vs. 58.3%; p = 0.03), with no significant differences in PFS (5 and 3 months, 95% CI: 1–6 vs. 2–5; p = 0.6) and OS (12 and 4 months, 95% CI: 3‐NR vs. 2‐NR; p = 0.2).ConclusionAfter treatment with both nivolumab and cabozantinib, the choice of a safe active systemic therapy offered better outcomes than BSC.

Second-line treatment with nivolumab, cabozantinib, regorafenib, or best supportive care in patients with advanced hepatocellular carcinoma: analysis at a Hispanic-majority NCI-designated cancer center.

In the last four years, six regimens were approved by the Food and Drug Association as second-line therapies for advanced hepatocellular carcinoma (HCC). However, there are significant differences between real-world and clinical trial populations. We analyzed survival and toxicities among second-line therapies for HCC in our population. We performed a retrospective cohort study of patients with advanced HCC who received second-line therapies (tyrosine kinase inhibitor or TKI; immunotherapy or IO) or best supportive care (BSC) at a tertiary-referral cancer center serving the South Texas region. Progression-free survival (PFS) was determined, and adverse events were compared between therapies. In our cohort, median age was 60 years (n=65), and 49 (75%) were Hispanic. 58 (89%) patients received second-line therapy. Child-Pugh (CP) score of cohort: A, 18%; B, 55%; C, 26%. Median PFS (mPFS) was 3.1 months with TKI (n=6), 3.3 months with IO (n=27), and 1.3 months with BSC (n=25). There was improved survival with IO compared to BSC [hazards ratio (HR) =0.31; 95% confidence interval (CI): 0.15-0.63; P=0.0014]. There was no significant difference comparing IO to TKI (HR =0.94; 95% CI: 0.31-2.86; P=0.92), but a trend to improved PFS with TKI when compared to BSC (HR =0.33; 95% CI: 0.10-1.04; P=0.058). TKI group had significantly more rash (P=0.01) and hand-foot syndrome (P<0.001) compared to IO and BSC. Our Hispanic-majority cohort with varying liver dysfunction, including CP-B & C cirrhosis, were more likely to receive IO or BSC. Both second-line treatment groups, IO or TKI, demonstrated increased mPFS compared to BSC and were tolerable compared to BSC, with expected toxicity per class of drug.

Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial

Novel adjuvant strategies are needed to optimise outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). We aimed to evaluate adjuvant atezolizumab versus best supportive care after adjuvant platinum-based chemotherapy in these patients. IMpower010 was a randomised, multicentre, open-label, phase 3 study done at 227 sites in 22 countries and regions. Eligible patients were 18 years or older with completely resected stage IB (tumours ≥4 cm) to IIIA NSCLC per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system (7th edition). Patients were randomly assigned (1:1) by a permuted-block method (block size of four) to receive adjuvant atezolizumab (1200 mg every 21 days; for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence) after adjuvant platinum-based chemotherapy (one to four cycles). The primary endpoint, investigator-assessed disease-free survival, was tested hierarchically first in the stage II-IIIA population subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells (SP263), then all patients in the stage II-IIIA population, and finally the intention-to-treat (ITT) population (stage IB-IIIA). Safety was evaluated in all patients who were randomly assigned and received atezolizumab or best supportive care. IMpower010 is registered with ClinicalTrials.gov, NCT02486718 (active, not recruiting). Between Oct 7, 2015, and Sept 19, 2018, 1280 patients were enrolled after complete resection. 1269 received adjuvant chemotherapy, of whom 1005 patients were eligible for randomisation to atezolizumab (n=507) or best supportive care (n=498); 495 in each group received treatment. After a median follow-up of 32·2 months (IQR 27·4-38·3) in the stage II-IIIA population, atezolizumab treatment improved disease-free survival compared with best supportive care in patients in the stage II-IIIA population whose tumours expressed PD-L1 on 1% or more of tumour cells (HR 0·66; 95% CI 0·50-0·88; p=0·0039) and in all patients in the stage II-IIIA population (0·79; 0·64-0·96; p=0·020). In the ITT population, HR for disease-free survival was 0·81 (0·67-0·99; p=0·040). Atezolizumab-related grade 3 and 4 adverse events occurred in 53 (11%) of 495 patients and grade 5 events in four patients (1%). IMpower010 showed a disease-free survival benefit with atezolizumab versus best supportive care after adjuvant chemotherapy in patients with resected stage II-IIIA NSCLC, with pronounced benefit in the subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells, and no new safety signals. Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC. F Hoffmann-La Roche and Genentech.

Coronavirus disease 2019 respiratory failure: what is the best supportive care for patients who require ICU admission?

Purpose of reviewCurrently, there is no cure for SARS-CoV-2 infection, yet hospital mortality rates for COVID-19 have improved over the course of the pandemic and may be due in part to improved supportive care in the ICU. This review highlights the evidence for and against various ICU supportive therapies for the treatment of critically ill patients with COVID-19.Recent findingsEarly in the pandemic, there was great interest in novel ICU supportive care, both for the benefit of the patient, and the safety of clinicians. With a few exceptions (e.g. prone ventilation of nonintubated patients), clinicians abandoned most of these approaches (e.g. early intubation, avoidance of high flow or noninvasive ventilation). Standard critical care measures, especially for the treatment of severe viral respiratory infection including acute respiratory distress syndrome (ARDS) were applied to patients with COVID-19 with apparent success.SummaryIn general, the COVID-19 pandemic reaffirmed the benefits of standard supportive care for respiratory failure and in particular, recent advances in ARDS treatment. Prone ventilation of nonintubated patients, an approach that was adopted early in the pandemic, is associated with improvement in oxygenation, but its impact on clinical outcome remains unclear. Otherwise, prone mechanical ventilation and avoidance of excessive tidal volumes, conservative fluid management, antibiotic stewardship and early evaluation for extracorporeal membrane oxygenation (ECMO) -- basic tenants of severe respiratory infections and ARDS care -- remain at the core of management of patients with severe COVID-19.

Low-Dose Cytarabine versus Best Supportive Care for Patients with Acute Myeloid Leukaemia Unfit for the Standard of Care: Egyptian Centre Experience

Background: Acute myeloid leukaemia (AML) in the elderly is not strong enough to tolerate aggressive chemotherapy. We conducted the present study to compare the efficacy and safety of low-dose cytarabine (LDAC) with best supportive care (BSC) in Egyptian patients. Method: A prospective randomized study included 60 eligible patients aged over 60 years with newly diagnosed AML. They were randomized to receive LDAC or BSC. The overall survival (OS) was the primary endpoint, while the secondary endpoint was to compare the quality of life in the form of a length of hospital stays (LOHS), mode and frequency of admission in the two studied groups. Results: Herein, 30 patients received LDAC and 30 patients received BSC. The mean survival time was 7.5 months in the BSC group compared with 10.2 months in the LDAC group. Even though the median OS was 8.4 months in the BSC group, it did not reach in the LDAC group; HR= 2.047, CI 95% (0.541-7.743) (P=0.2). There was a statistically significant association with LDAC and the frequency of hospital admission through the emergency department (ED) due to neutropenic fever and prolonged LOHS (P<0.001, P<0.002, and P<0.001, respectively). Meanwhile, the admission through the outpatient clinic (OPC) and for transfusion support were statistically insignificant in the two groups (P< 0.12 and P< 0.6, respectively). Conclusion: Despite, there were no OS statistically significant benefits of the use of LDAC over BSC in our patients, poor quality of life in the form of frequent admission through the ED, more incidence of neutropenic fever, and prolonged LOHS were reported more to patients received LDAC.