Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We ...performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies,
= 16; patients,
= 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24-1.91;
= 0.01 and HR = 1.34, 95% CI: 1.02-1.76;
= 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41-4.43;
< 0.01) or brain metastases (HR = 1.51, 95% CI 1.22-1.87;
< 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We analyzed published studies on the efficacy and safety of the third dose of the COVID‐19 vaccine in various general population settings. We conducted systematic searches of PubMed and EMBASE for ...series published in the English language through November 15, 2021, using the search terms “third” or “booster” or “three” and “dose” and “COVID‐19” or “SARS‐CoV‐2.” All articles were selected according to the MOOSE guidelines. The seroconversion risk after third doses was descriptively expressed as a pooled rate ratio (seroconversion rate after the third dose/seroconversion rate after the second dose). The search returned 30 studies that included a total of 2 734 437 vaccinated subjects. In more than 2 700 000 Israeli patients extracted from the general population, the reduction in the risk of infection ranged from 88% to 92%. Conversion rates for IgG anti‐spike ranged from 95% to 100%. In cancer or immunocompromised patients, mean IgG seroconversion was 39.4% before and 66.6% after third doses. A third dose seems necessary to protect against all COVID‐19 infection, severe disease, and death risk.
Highlights
We analyzed published studies on the efficacy and safety of the third dose of COVID‐19 vaccine in various settings.
A total of 30 studies that included a total of 2 734 437 vaccinated subjects.
The reduction in the risk of infection ranged from 88% to 92%.
In immunocompromised patients, mean IgG seroconversion was 39.4% before and 66.6% after third doses.
A third dose seems necessary to protect against all COVID‐19 infection, severe disease, and death risk.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Platinum agents such as cisplatin and carboplatin are DNA-damaging agents with activity in breast cancer (BC), particularly in the triple negative (TN) subgroup. The utility of platinum agents, in ...addition to standard neoadjuvant chemotherapy (NAC), is controversial. To assess the activity of platinum agents in patients with TNBC treated with NAC, we performed a systematic review and meta-analysis of all published studies. A search of PubMed, EMBASE, the Web of Science, SCOPUS, and the Cochrane Central Register of Controlled Trials was performed to identify studies that investigated platinum-based NAC in patients with TNBC. Random effect models were adopted to estimate the summary risk ratio (RR), and the publication bias was evaluated using a funnel plot and Egger’s regression asymmetry test. The primary endpoints were the pooled rate of the pathologic complete response (pCR) and the RR to obtain a pCR in patients treated versus not treated with NAC containing platinum agents. 28 studies were included (six randomized controlled trials and 22 retrospective or prospective studies) for a total of 1,598 TNBC patients. Overall, the pooled rate of pCR in patients treated with platinum-based NAC was 45 %. In randomized trials, NAC containing cisplatin or carboplatin significantly increased the rate of pCR compared with nonplatinum agents (RR = 1.45, 95 % CI 1.25–1.68;
P
< 0.0001). Compared with non-TN, TNBCs were associated with a threefold increase in the pCR rate when treated with platinum-based NAC (RR 3.32, 95 % CI 2.39–4.61;
P
< 0.0001). In conclusion, pCR rates increase significantly with the addition of cisplatin or carboplatin in TNBC compared with NAC containing no platinum drugs. TN status is a predictor of benefit from platinum-based NAC.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Importance of the field: Taxanes are agents for the treatment of breast cancer. Paclitaxel is hydrophobic, and available formulations require polyoxyethylated castor oil, Cremphor EL® (CrEL) and an ...ethanol vehicle to allow parental administration. Nanoparticle albumin-bound paclitaxel (nab-P) is a CrEL-free formulation of paclitaxel. The human albumin-stabilized paclitaxel particles have a size of approximately 130 nm, which allows intravenous infusion without capillary blockage.
Areas covered in this review: Efficacy and safety of nab-P in breast cancer has been compared with paclitaxel and docetaxel in large Phase III and II trials. Additionally, the efficacy and safety of nab-P have been investigated in other single-arm clinical trials, in early and advanced disease.
What the reader will gain: Preclinical and clinical development of the drug across all clinical trials published so far, the approved clinical indications, the benefits of this taxane formulation and a look into the future with emphasis on the application in specific subtypes of breast cancer.
Take home message: nab-P has been approved for the treatment of metastatic breast cancer in patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline-containing therapy is not indicated and represents one of most authoritative and sophisticated applications of nanotechnology in cancer treatment so far.
Patients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK ...inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs.
A systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR).
A total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17% (95%CI 13.1-65.2%), while the pooled IC ORR observed in further lines was 44.2% (95%CI 33.3-55.1%). Intracranial disease control rate (IC DCR) was 70.3% and 78.2% in naïve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0%.
Based on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: The outbreak of COVID-19 poses an unprecedented challenge to global public health. Patients with cancer are at a higher risk during the SARS-CoV-2 pandemic. Patients with lung cancer ...and COVID-19 were compared to those without cancer and those with other malignancies for the main outcome of this study. The aim of this study was to evaluate the differences in susceptibility, disease severity, and mortality between lung cancer patients and the general population. Methods: Using PRISMA reporting guidelines, we conducted a systematic review and meta-analysis of the published literature. The Cochrane Library database, PubMed, EMBASE, and PubMed Central were comprehensively searched for published papers until 31 May 2022. A pooled risk ratio (OR) with 95% CI was presented as the result of this meta-analysis. Results: We included 29 studies involved 21,257 patients with lung cancer and SARS-CoV-2 infection. Analysis data showed that mortality in patients with lung cancer was significantly higher than that in patients without cancer (HR = 2.00 95%CI 1.52, 2.63, p < 0.01) or with other malignancies (HR = 1.91 95%CI 1.53, 2.39, p < 0.01). In addition, we also observed a higher risk of severe infection in terms of life-threatening or required ICU admission/mechanical ventilation for lung cancer patients (HR = 1.47 95%CI 1.06, 2.03, p = 0.02) than for patients with no cancer or other malignancies. Regarding lung cancer as a risk factor for acquiring SARS-CoV-2 infection, we could not reach statistical significance (hazard ratio HR =2.73 95%CI 0.84, 8.94, p = 0.1). Conclusion: Lung cancer represents an important comorbidity and modifies COVID-19 prognosis in terms of disease severity and mortality. More patients experience severe or even fatal events. Considering their inherent fragility, patients with lung cancer, and generally all oncological populations, should be treated more carefully during the COVID-19 pandemic.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Background Radical prostatectomy (RP) is one of the treatment options for localized, high-risk prostate cancer (PC), but it has never been compared with external beam radiotherapy (RT), ...which is an alternative approach, in a large randomized trial. To compare the outcomes of patients treated with surgery versus RT, we performed a metaanalysis of available studies on this topic. Materials and Methods We performed a search of MEDLINE, EMBASE, Web of Science, SCOPUS, and The Cochrane Central Register of Controlled Trials (CENTRAL) for randomized or observational studies that investigated overall survival (OS) and PC-specific mortality (PCSM) risks in relation to use of surgery or RT in patients with high-risk PC. Fixed- and random-effect models were fitted to estimate the summary odds ratio (OR). Between-study heterogeneity was tested using χ2 statistics and measured using the I2 statistic. Publication bias was evaluated using a funnel plot and Egger regression asymmetry test. Results Seventeen studies were included (1 randomized and 16 retrospective). RP was associated with improved OS (OR, 0.51; 95% confidence interval CI, 0.38-0.68; P < .00001), PCSM (OR, 0.56; 95% CI, 0.37-0.85; P = .007), and non-PCSM (OR, 0.53; 95% CI, 0.35-0.8; P = .002) compared with RT. Biochemical relapse-free survival rates were similar to those of RT. Conclusion Overall and cancer-specific mortality rates appear to be better with RP compared with RT in localized, high-risk PC. Surgery is also associated with a 50% decreased risk of non-PCSM compared with RT.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Introduction:
The typical class side effect of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (panitumumab and cetuximab) is a cutaneous maculopapular rash, although ...hypomagnesemia is also described to be a frequent adverse event. The purpose of our meta-analysis is to evaluate the frequency and the relative risk of hypomagnesemia in patients treated with cetuximab or panitumumab in randomized trials.
Area covered:
Eligible studies included prospective randomized Phase III controlled trials in which cetuximab or panitumumab were compared with standard anti-neoplastic therapy or best supportive care. Summary incidence rates and relative risks with 95% confidence intervals were calculated.
Expert opinion:
The overall incidence of hypomagnesemia was 17% among the patients who received the treatment, whose risk of developing hypomagnesemia turned out to be significantly increased compared with the patients treated with control medication, with an overall relative risk of 5.83 (p < 0.00001), where 3.87 refers to cetuximab and 12.55 to panitumumab. The addition of anti-EGFR monoclonal antibodies to standard anticancer therapy showed a significantly increased risk of hypomagnesemia compared with controls. The risk seems to be even higher for panitumumab, probably correlated with the increased risk of other adverse events (e.g., diarrhea and dehydration). Hypomagnesemia does not seem to be linked with any serious complications.
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for ...metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC.
We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS.
The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72–0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69–0.91; p < 0.01). No OS data were available for patients ≥70 years.
This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.
•Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have changed the treatment of hormone-sensitive breast cancer (BC).•We performed a pooled analysis to validate the survival benefit of adding anti-CDK4/6 inhibitors in older patients.•The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials.•The addition of CDK4/6 inhibitors significantly reduced the mortality risk by 21% in older BC patients.•This pooled analysis demonstrates that CDK4/6 inhibitors confer OS benefit in elderly patients with advanced ER+ BC.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
