Different Chemotherapy Regimens and Pathologic Complete Response in Triple-Negative Breast Cancer: An Updated Network Meta-Analysis of Phase 3 Trials.

Background and Objectives: Currently, the standard treatment for non-metastatic triple-negative breast cancer (TNBC) consists of a systemic neoadjuvant (or perioperative) anthracycline plus taxane-based chemotherapy, delivered either sequentially or concomitantly. We performed a network meta-analysis (NMA) to compare the relative efficacy of different neoadjuvant treatments for TNBC in terms of pathologic complete response (pCR). Materials and Methods: The MEDLINE, Embase, and Cochrane databases were searched from database inception to 1 November 2023. Randomized clinical trials were used that enrolled adults with stage I-III TNBC and provided data on pCR defined as residual ypT0/TisN0M0. Between-group comparisons were estimated using risk ratios (RRs) with 95% credible intervals (95% CrIs). The primary outcome was the pCR rate. Results: 1129 citations were screened, and 12 randomized clinical trials were included. In Bayesian comparisons, all regimens, except anthracycline/taxanes plus gemcitabine or capecitabine, resulted in a higher pCR than the standard regimen in both direct and indirect comparisons. In particular, immunotherapy-based regimens resulted in more than double the pCR compared to historical regimens (RR = 2.3, 95% CI 1.9-2.9) and ranked as being the optimal regimen with a probability of 97%. Disease-free survival was better for immune checkpoint inhibitor-based chemotherapy (HR = 0.36, 95% 1.21-2.09) than for historical regimens. Conclusion: This meta-analysis confirmed that incorporating immunotherapy with neoadjuvant platinum-based chemotherapy is the best option to guarantee remarkable pathologic downstaging and improve clinical outcomes.

Third dose of SARS-CoV-2 vaccine: A systematic review of 30 published studies.

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.

Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials.

BACKGROUND: Several trials have demonstrated the benefit of anti-CDK4/6 inhibitors plus endocrine therapy in estrogen receptor-positive (ER+) advanced breast cancer (BC), in first or subsequent lines of therapy. However, due to the lack of direct/indirect comparisons, there are no data demonstrating the superiority of one drug over the other. We compared the effectiveness of palbociclib, ribociclib, and abemaciclib in advanced ER + BC via an indirect adjusted analysis. METHODS: We performed electronic searches in the PubMed, EMBASE, and Cochrane databases for prospective phase 3 randomized trials evaluating anti-CDK4/6 inhibitors plus endocrine agents. We compared the results with an adjusted indirect analysis of randomized-controlled trials. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR) and G3-4 toxicities occurring in ≥ 5% of patients. RESULTS: Six trials and six treatment arms including a total of 3743 participants, were included. For PFS and ORR analysis, the three agents were similar in both first- and second-line studies. All G3-4 toxicities were similar, with reduced risk of diarrhea for palbociclib versus abemaciclib (relative risk [RR] 0.13, 95% CI 0.02-0.92; P = 0.04) and of QTc prolongation for palbociclib versus ribociclib (RR 0.02, 95% CI 0-0.83; P = 0.03). Despite different inclusion criteria and length of follow-up, similar features were noticed among second-line studies with the exception of increased risk of anemia G3-4 and diarrhea G3-4 for abemaciclib. CONCLUSIONS: Based on PFS and ORR results of this indirect meta-analysis, palbociclib, ribociclib, and abemaciclib are equally effective in either first- or second-line therapy for advanced ER + BC. They, however, ported different toxicity profiles.

Neoadjuvant dose-dense chemotherapy for locally advanced breast cancer: a meta-analysis of published studies.

Large operable or locally advanced breast cancers (BCs) are usually treated with neoadjuvant chemotherapy (CT) before surgery. However, there is no evidence to support an improvement in efficacy with dose-dense (DD) CT in this setting. We, therefore, carried out a meta-analysis to investigate whether DD-CT was more effective than the reference (every 3 weeks anthracyclines±taxanes) standard-dose CT as neoadjuvant treatment for BC. We searched Pubmed, SCOPUS, EMBASE, the Web of Science, CINAHL, and the Cochrane Central Register of Controlled Trials for randomized trials comparing conventional versus DD neoadjuvant CT for BC. Odds ratios (ORs) for pathologic complete responses (ypT0N0M0: pCR) and hazard ratios (HRs) of death and recurrence [overall survival (OS), and disease-free survival (DFS)] were estimated and pooled. A QUADAS-2 report for all studies included in the final analysis was tabulated for the risk of bias and applicability. A total of six randomized trials fulfilled the inclusion criteria. The pooled rates of the pCR were 13.5 and 9.2% in the experimental and control arms. A significant increase in the pCR [OR=1.55, 95% confidence interval (CI) 1.18-2.02, P=0.001] was noted with neoadjuvant DD-CT. However, the patients who received DD-CT did not have significantly better DFS and OS rates (DFS: HR=0.88, 95% CI 0.76-1.01, P=0.06; OS: HR=0.89, 95% CI 0.78-1.02, P=0.08). Even with the limitation of a relatively short follow-up period, this meta-analysis shows that DD neoadjuvant CT, despite not leading to a significant increase in survival, increases by 46.7% the possibility of achieving a pCR in operable and locally advanced BC. This treatment should thus be considered one of the backbone treatments of choice when neoadjuvant therapy is planned.

Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials.

Dose-dense (DD) chemotherapy (CT) aimed at achieving a higher rate of cancer cell destruction has been adopted as an adjuvant therapy in high-risk breast cancer (BC), with the goal being to improve outcomes. We performed an updated systematic review and meta-analysis of the existing data from randomized phase III trials regarding the efficacy and toxicity of this adjuvant DD-CT strategy in early BC. Randomized-controlled trials that compared a DD with a standard adjuvant CT schedule in adult women with resected BC were identified by searching the databases of Pubmed, the Cochrane Cancer Register of Controlled Trials, SCOPUS, EMBASE, and the Web of Science up to March 2015. Hazard ratios (HRs) of death and recurrence, and the relative risks of adverse events, were estimated and pooled. A total of 8 phase III trials encompassing 17,188 randomized patients met the inclusion criteria. The patients who received DD-CT had better overall survival (OS: HR 0.86, 95 % confidence interval [CI] 0.79-0.93, P = 0.0001) and disease-free survival (DFS: HR 0.84, 95 % CI 0.77-0.91, P < 0.0001) than those on the conventional schedule. A statistically significant OS benefit was observed in patients with hormone receptor-negative (ER-) tumors (HR 0.8, P = 0.002), but not in those with ER-positive BC (HR 0.93, 95 % CI 0.82-1.05; P = 0.25). DD-CT leads to better OS and DFS, particularly in women with ER- early BC. These results suggest that the DD strategy should be the standard care offered to high-risk ER- BC patients.

Efficacy of fourth-line chemotherapy in advanced non-small-cell lung cancer: a systematic review and pooled analysis of published studies.

There are no agents labelled for use as fourth-line therapy for non-small-cell lung cancer, even though it is currently prescribed in about 5-10% of patients. Here, we provide a pooled analysis of published studies on the efficacy of treatments in patients who have had at least three unsuccessful lines of therapy. The literature search was performed on Pubmed, EMBASE, the Web of Science, SCOPUS, CINAHL, Google Scholar and the Cochrane Library using the terms 'lung cancer' OR NSCLC AND 'fourth line'. The response rates and disease control rates were pooled using a random-effect or a fixed-effect model according to heterogeneity. Median progression-free survival and overall survival data were also collected and aggregated to obtain pooled median values of the included studies. Overall, 14 studies (673 patients), which were almost entirely published by Asian institutions, were eligible for this pooled analysis. Among these were two phase II trials and 12 retrospective cohort series. In general, the pooled overall response rate was 13.6% [95% confidence interval (CI) 10-18.3] and the pooled overall disease control rate was 47.3% (95% CI 38-56.9). The pooled median progression-free survival for these studies was 3.34 months (95% CI 2.42-4.27). The pooled median overall survival for these studies was 10.5 months (95% CI 9.57-11.52). In conclusion, for non-small-cell lung cancer patients who have undergone three or more unsuccessful lines of therapy, fourth-line treatment could be offered in select cases to those with a good performance status.

Hepatic resection for gastric cancer liver metastases: A systematic review and meta-analysis.

BACKGROUND: Resection of liver metastases from gastric cancer (GC) is rarely performed, and the outcome after hepatic surgery has not been systematically evaluated in the literature. The aim of this study was to perform a systematic review of outcome and prognostic factors for survival after liver metastasectomy for GC. METHODS: We performed a meta-analysis of published studies that focused on long-term outcomes (5-year overall survival [OS]) after surgical management of liver metastases from GC, and included more than 10 patients each. Pooled hazard ratios (HRs) were calculated for variables considered as potential prognostic factors for OS in at least three publications. RESULTS: Twenty-three studies comprising a total of 870 patients were considered in this analysis. The pooled weighted median OS was 22 months (95%CI 17.6-27.2). The pooled 5-year OS after liver resection was 23.8% (95%CI 19-29.3%). The pooled 5-year OS rates for metachronous and synchronous metastases were 30% (95%CI 24.7-35.8%) and 22.6% (95%CI 14-34.4%), respectively. Parameters associated with poor survival were (i) multiple metastases, and (ii) large size of metastases. CONCLUSIONS: Hepatic resection of GC liver metastases is associated with an acceptable 5-year OS, in particular after surgery of metachronous lesions, and could be offered to selected patients.

Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies.

BACKGROUND: In cancer cells, metabolism is shifted to aerobic glycolysis with lactate production coupled with a higher uptake of glucose as the main energy source. Lactate dehydrogenase (LDH) catalyzes the reduction of pyruvate to form lactate, and serum level is often raised in aggressive cancer and hematological malignancies. We have assessed the prognostic value of LDH in solid tumors. MATERIAL AND METHODS: A systematic review of electronic databases was conducted to identify publications exploring the association of LDH with clinical outcome in solid tumors. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) were pooled in a meta-analysis. Pooled HRs were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided. RESULTS: Seventy-six studies comprising 22 882 patients, mainly with advanced disease, were included in the analysis. Median cut-off of serum LDH was 245 U/L. Overall, higher LDH levels were associated with a HR for OS of 1.7 (95% CI 1.62-1.79; p < 0.00001) in 73 studies. The prognostic effect was highest in renal cell, melanoma, gastric, prostate, nasopharyngeal and lung cancers (all p < 0.00001). HRs for PFS was 1.75 (all p < 0.0001). CONCLUSIONS: A high serum LDH level is associated with a poor survival in solid tumors, in particular melanoma, prostate and renal cell carcinomas, and can be used as a useful and inexpensive prognostic biomarker in metastatic carcinomas.

Long response to eribulin in breast cancer: a case report.

No definitive cure is available for metastatic breast cancer and current therapies mainly focus on symptom control and minimization of adverse events to extend survival and maintain a good quality of life. Current treatment options include hormonal and chemotherapeutic agents which are characterized by different toxicity profiles and are selected based on patients' performance status and prior therapies. Eribulin is a microtubule dynamic inhibitor which acts by sequestering tubulin molecules into aggregates, thus preventing microtubule growth and causing apoptosis. Many studies show that heavily pretreated metastatic breast cancer patients benefit from eribulin treatment both in terms of efficacy and for the favorable toxicity profile. In the Phase III EMBRACE study, eribulin treatment resulted in a significant improvement in overall survival. We report here the case of a patient who experienced a time to progression of several months with eribulin after three lines of chemotherapy and two lines of hormonal therapy.

The value of platinum agents as neoadjuvant chemotherapy in triple-negative breast cancers: a systematic review and meta-analysis.

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.

Five or more years of adjuvant endocrine therapy in breast cancer: a meta-analysis of published randomised trials.

Five years of adjuvant hormonal therapy is the standard of care in early breast cancer (BC) expressing oestrogen receptors (ER+). Prolonged duration of adjuvant endocrine therapy is implemented to prevent recurrence and death; in particular, its carryover effect may prevent very late events. This meta-analysis compares the efficacy of 5 years of hormonal therapy alone with that of additional years of hormonal therapy, in patients with early BC. Randomised trials comparing 5 years versus more than 5 years of hormonal therapy in BC were identified by electronic searches of PubMed, EMBASE, ISI Web of Science and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using the fixed- or random-effects models. The primary endpoints were overall survival (OS), BC-specific survival (BCSS) and relapse-free survival (RFS) reported as odds ratios (ORs) and 95 % confidence interval (CI). Eight trials, including 29,138 patients, were identified. Overall, in ER+ BCs, extended endocrine therapy beyond 5 years of tamoxifen significantly improved OS (OR, 0.89; 95 % CI 0.80-0.99; P = 0.03), BCSS (OR, 0.78; 95 % CI 0.69-0.9; P = 0.0003) and RFS (OR 0.72; 95 % CI 0.56-0.92; P = 0.01) compared with 5 years of hormonal therapy alone. Loco-regional and distant relapses were reduced by 36 and 13 %, respectively. Compared with 5 years of tamoxifen, additional adjuvant endocrine therapy reduced risk of death and relapse of ER+ BC by ~10 and 30 %, respectively. This strategy should be considered in patients free of disease after 5 years of hormonal therapy.

The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prognostic Value of HER2-low Status in ER+ Early Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND/AIM: Low human epidermal growth factor receptor 2 expression (HER2-low: 1+/2+ by immunohistochemistry without HER2 amplification) is emerging as defining a specific breast cancer (BC) subgroup owing to its distinct biological features. However, its prognostic role has not been confirmed in clinical practice. We conducted a systematic review and meta-analysis to determine the prognostic role of HER2-low status in patients with estrogen receptor-positive (ER+) early BC. MATERIALS AND METHODS: We searched PubMed, EMBASE, and the Cochrane Library for prospective or retrospective studies that reported data on overall (OS) or disease-free (DFS) survival for HER2-low compared to HER2-negative BC. Data were pooled using hazard ratios (HR) with confidence intervals (CI) for OS/DFS of HER2-low vs. HER2-negative subgroups according to the random-effects model. OS was the primary outcome measure, and DFS and pathological complete response were the secondary endpoints. RESULTS: An analysis was made of 25 studies collected, including 34,965 patients with HER2-low BC. A HER2-low status was associated with an HR for OS of 0.83 (95% CI=0.76-0.9, p<0.0.01). Similarly, a pooled HR of 0.89 (95% CI=0.840.94, p<0.0.01) showed that patients with HER2-low BC had an increased DFS. Pathological complete response was significantly lower in HER2-low BC in 13 studies (OR=0.72, 95% CI=0.58-0.91; p<0.01). CONCLUSION: Based on these data, HER2-low status should be identified as a potential prognostic factor in early stage ER+ BC. This should be taken into account when considering treatment in (neo)adjuvant settings, and it should be a potential stratification factor in future investigations.

Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses.

BACKGROUND: The immune system (innate and adaptive) is influenced by vitamin D3, which affects gene expression and inflammatory pathways. An umbrella review was conducted to evaluate the power and accuracy of data connecting vitamin D3 to the outcomes of COVID-19 infection and to appraise the proof provided by published meta-analyses. METHODS: MEDLINE, Embase, and the Cochrane Library were searched from database inception to 31 May 2022. Meta-analyses of prospective or retrospective observational studies and randomized trials were included. Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. RESULTS: From 74 publications, 27 meta-analyses described five associations between vitamin D3 levels and supplementation and COVID-19 outcomes. Low levels of vitamin D3 were significantly associated with severity (highly suggestive evidence; OR = 1.97 [95% CI, 1.55-2.51], p < 0.01; I2 = 77%, p < 0.01) and mortality risk due to COVID-19 disease (OR = 1.83 [95% CI, 1.55-2.16], p < 0.01; I2 = 50%, p < 0.01). Vitamin D3 supplementation, after a diagnosis of COVID-19 infection, was associated with significantly reduced infection severity (e.g., ICU admission) and mortality. CONCLUSIONS: This umbrella review of the available evidence suggests that insufficient vitamin D3 may increase COVID-19 infection risk, severity, and mortality, in addition to showing a highly suggestive association between vitamin D3 supplementation and reduced severity and mortality among infected patients.

Ribociclib in the Treatment of Hormone-Receptor Positive/HER2-Negative Advanced and Early Breast Cancer: Overview of Clinical Data and Patients Selection.

Among pre- and postmenopausal women with hormone receptor-positive (HR+) breast cancer (BC), combinations of an aromatase inhibitor (AI) or fulvestrant with a CDK 4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) have demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard single-agent hormone therapy alone as first-line therapy for de novo metastatic disease or relapse during or after adjuvant therapy and no previous therapies in an advanced setting. We here reviewed clinical data about ribociclib in advanced and early BC. Also, we shed light on patient selection and special settings in which medical oncologists urgently await an advance in treatment. Ribociclib was FDA-approved in combination with letrozole based on a Phase III study in which 668 postmenopausal women with HR+, HER2-negative recurrent or metastatic BC were treated with first-line letrozole with or without ribociclib. For patients with metastatic disease at presentation or after a course of AIs, the results of the MONALEESA-3 trial suggest ribociclib's efficacy in combination with fulvestrant, and this combination is FDA-approved for initial- and subsequent-line endocrine therapy for postmenopausal women with metastatic hormone receptor-positive, HER2-negative BC. In adjuvant and neoadjuvant settings, the use of CDK 4/6 inhibitors may be useful to boost outcomes in high-risk patients with HR+ BC, but data contrast with those of a phase III study, which produced positive results. New combinations are being explored in upfront disease (neoadjuvant) or in association with other targeted agents in metastatic disease. Compared to other CDK 4/6 available, ribociclib has a higher incidence of liver function test abnormalities than the other agents and can cause QTc prolongation, and therefore may be prudently avoided in patients with cardiac morbidities or other risk factors for QTc prolongation (drugs, interactions). In these cases, different agents (palbociclib or abemaciclib) may be used. In conclusion, ribociclib with letrozole or with fulvestrant is effective for the entire spectrum of patients with HR+ BC in the advanced setting. Ribociclib has all the characteristics of an innovative drug able to change the clinical practice and most BC patients' prognoses.

COVID-19 and Lung Cancer Survival: An Updated Systematic Review and Meta-Analysis.

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.

Neoadjuvant chemotherapy and concomitant trastuzumab in breast cancer: a pooled analysis of two randomized trials.

The aim of this meta analysis was to evaluate the benefit of adding concomitant trastuzumab to neoadjuvant(anthracycline and taxane-based) chemotherapy, which was assessed based on two published randomized controlled trials. The eligible patients were randomized to receive either neoadjuvant chemotherapy alone or with concurrent administration of trastuzumab. Relative risks(RRs) with 95% confidence intervals of pathologically complete response in breast and nodes, relapse-free survival, overall survival, and cardiotoxicity were calculated.The RR of obtaining a pathologically complete response in breast and nodes was 2.07 in the experimental arms(1.41­3.03; P = 0.0002; P for heterogeneity 0.63; fixed effect model). The RR of being disease free was 0.67 in favor of the experimental arms (0.48­0.94; P = 0.02; P for heterogeneity 0.22; fixed affect model). The RR of being alive was 0.67 in favor of the experimental arms (0.39­1.15;P= 0.15). The RR of a cardiac event was 1.09 in the arms treated with chemotherapy and concomitant trastuzumab, but that is not significant (0.6­1.98; P =0.77). The addition of concomitant trastuzumab to neoadjuvant chemotherapy doubles the risk of obtaining a pathologically complete response in both breast and nodes compared with controls. Trastuzumab significantly reduces the risk of relapse and does not increase the risk of cardiotoxicity,despite being associated with anthracyclines. The largest benefit was observed in a locally advanced patient study.

Cetuximab and panitumumab in KRAS wild-type colorectal cancer: a meta-analysis.

BACKGROUND: Anti-epidermal growth factor receptor monoclonal antibodies (panitumumab [P] and cetuximab [C]) are approved and effective only in KRAS wild-type patients with advanced colorectal cancer. The purpose of our meta-analysis is to evaluate the real effects of C and P in KRAS wild-type patients treated in randomized trials. PATIENTS AND METHODS: Eligible studies included prospective, randomized, and controlled trials in which either C or P had been added to standard antineoplastic therapy or best supportive care and data for KRAS wild-type patients only had been calculated. Six thousand three hundred ninety-five patients' tumor samples have been analyzed (total wild-type n = 3,254; experimental arm n = 1,608; control arm n = 1,646). Relative risks (RRs) with 95% confidence intervals (CIs) for response rate were calculated, as well as hazard ratios (HRs)for progression-free survival (PFS) and overall survival. RESULTS: The overall RR of response rate is 1.69 (p = 0.003) in all trials. The overall HRs for PFS and survival are 0.65 (p = 0.0006) and 0.84 (p = 0.03), respectively, and both are significant. The HRs for PFS and survival in C trials are 0.64 and 0.79, respectively, and 0.65 and 0.87, respectively, in P trials, although only the results achieved in P trials are significant (p = 0.0007 and p = 0.03). Both response rate (RR = 10.94) and PFS (HR = 0.51) have increased more in pretreated patients than in first-line trials. CONCLUSION: The addition of anti-EGFR monoclonal antibodies to standard anticancer therapy in KRAS wild-type colorectal cancer showed an overall significantly increased risk of objective response rate and increased progression-free and overall survival. Only the results achieved in P randomized trials are significant, and the strongest results have been achieved in pretreated patients.

Lactobacillus Kefiri LKF01 (Kefibios®) for Prevention of Diarrhoea in Cancer Patients Treated with Chemotherapy: A Prospective Study.

Diarrhoea is one of the main side effects that cancer patients face. The literature showsthat the incidence of chemotherapy (CT)-induced diarrhoea (grade 3-4) in treated patients is in the range of 10-20%, particularly after 5-fluorouracil (5-FU) bolus or some combination therapies of irinotecan and fluoropyrimidines. The aim of the present study was to evaluate the clinical effectiveness of Lactobacillus kefiri LKF01 (Kefibios®) in the prevention or treatment of CT-related diarrhoea in the cancer population. We conducted a prospective observational study. Patients enrolled were adults treated for at least four months with 5-FU-based CT. Kefibios® was administered to patients every day. The primary outcome was the evaluation of the incidence of grade 3-4 CT-induced diarrhoea. We included 76 patients in the final analysis. A 6.6% incidence of high-grade diarrhoea was found in the evaluated population (4.7% of patients treated with 5-FU-based therapy and 8.5% of patients treated with capecitabine-based CT). The overall incidence of high-grade diarrhoea observed was higher in the 1st and 2nd cycles (3.9%), with a subsequent sharp reduction from the 3rd cycle (1.3%) and negativisation from the 5th cycle. Lactobacillus kefiri LKF01 (Kefibios®) is safe and effective in preventing severe diarrhoea in cancer patients receiving 5-FU or capecitabine-based treatment.

Survival of Colorectal Cancer Patients With Diabetes Mellitus: A Meta-Analysis.

OBJECTIVES: Diabetes mellitus (DM) is associated with an elevated risk of various cancers, including colorectal cancer (CRC). Similarly, pre-existing DM may also influence prognosis among patients with CRC. We performed a systematic review and meta-analysis to assess the association between DM and risk of death and relapse after a diagnosis of CRC. METHODS: PubMed, Scopus, Web of Science, The Cochrane Library and Embase were searched from inception until July 2019 for studies reporting prognosis of patients with DM and CRC. The primary outcome of the study refers to overall mortality in patients with vs without diabetes. Secondary endpoints were cancer-specific mortality and progression or relapse-free survival. The risk of death and relapse are reported as hazard ratio (HR) with 95% confidence interval (CI), and an HR >1 was associated with worst outcome in patients with diabetes compared to those without diabetes. RESULTS: Mortality and relapse associated with DM in patients with CRC were evaluated among 5,267,980 participants (total of 82 studies). Overall, concomitant diagnosis of CRC and DM were associated with an independent increased risk of overall mortality (HR, 1.21; 95% CI, 1.17 to 1.25; p<0.01) and CSM (HR, 1.11; 95% CI, 1.05 to 1.17; p<0.01). Patients were also at increased risk of relapse (HR, 1.09; 95% CI, 1.02 to 1.16; p<0.01). CONCLUSIONS: In CRC patients with DM, diabetes decreased survival and increased the risk of relapse. Adequate control of lifestyle choices, more intensive follow ups, use of some oral antidiabetics, dietary restrictions, physical activity and monitoring of diabetes-associated complications are measures for reducing mortality in this setting.