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The role of noninvasive positive pressure ventilation (NIPPV) in COVID-19 patients with acute hypoxemic respiratory failure (AHRF) is uncertain, as no direct evidence exists to support NIPPV use in such patients. We retrospectively assessed the effectiveness and safety of NIPPV in a cohort of COVID-19 patients consecutively admitted to the COVID-19 general wards of a medium-size Italian hospital, from March 6 to May 7, 2020. Healthcare workers (HCWs) caring for COVID-19 patients were monitored, undergoing nasopharyngeal swab for SARS-CoV-2 in case of onset of COVID-19 symptoms, and periodic SARS-CoV-2 screening serology. Overall, 50 patients (mean age 74.6 years) received NIPPV, of which 22 (44%) were successfully weaned, avoiding endotracheal intubation (ETI) and AHRF-related death. Due to limited life expectancy, 25 (50%) of 50 NIPPV-treated patients received a “do not intubate” (DNI) order. Among these, only 6 (24%) were weaned from NIPPV. Of the remaining 25 NIPPV-treated patients without treatment limitations, 16 (64%) were successfully weaned, 9 (36%) underwent delayed ETI and, of these, 3 (33.3%) died. NIPPV success was predicted by the use of corticosteroids (OR 15.4, CI 1.79–132.57, p 0.013) and the increase in the PaO2/FiO2 ratio measured 24–48 h after NIPPV initiation (OR 1.02, CI 1–1.03, p 0.015), while it was inversely correlated with the presence of a DNI order (OR 0.03, CI 0.001–0.57, p 0.020). During the study period, 2 of 124 (1.6%) HCWs caring for COVID-19 patients were diagnosed with SARS-CoV-2 infection. Apart from patients with limited life expectancy, NIPPV was effective in a substantially high percentage of patients with COVID-19-associated AHRF. The risk of SARS-CoV-2 infection among HCWs was low.

BackgroundSingle-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.MethodsWe conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50%.ResultsOne thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p < 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90%, as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis.ConclusionPembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.

(1) Background: Drug development in oncology is changing rapidly. The aim of the present study was to provide an insight into the features of anti-tumor drugs approved in Europe; (2) Methods: We included all the indications for solid tumors issued by the European Medicines Agency (EMA) between 2015 and 2020. We extracted data from European Public Assessments Reports (EPAR), including drug name, mechanism of action, setting, features of pivotal clinical trials, primary end-points, quality of life (QoL); (3) Results: In the explored period, EMA issued 132 new indications (81 indications’ extensions) for 62 oncology drugs. In about half of indications (47%), the approval was biomarker-based. Immune check point inhibitors (ICIs) and signal transduction inhibitors were the two most representative drug categories (62%). Most of the indications were for the advanced setting (91%) and front-line therapy (66%). The most common tumor types were non-small cell lung cancer (24%), breast (16%), and melanoma (10%). Two thirds of the indications (73%) were approved based on phase III trials. Overall survival (OS) represented the primary end-point only in 39% of indications, mainly limited to advanced setting (98%) and ICI trials (80%). Almost all (94%) cell cycle and DNA repair mechanism inhibitors were approved based on progression free survival (PFS) data. In pivotal trials with signal transduction inhibitors, objective response rate (ORR) was the prevalent (45%) primary end-point. QoL was never considered as primary end-point; (4) Conclusions: In this analysis, we intended to offer an updated picture of the recent drug development in oncology. Most of the efforts led to broadening indications of pre-existing molecules, with signal transduction inhibitor and ICIs contending the leadership. Twenty-seven percent of the indication were approved without a phase III trial. The majority of drugs entered the market without evidence of OS or QoL benefit but based on surrogate outcomes.

Simple SummaryConsidering the high incidence and mortality of breast cancer, a lot of trials evaluating new drugs for the treatment of this disease are currently ongoing. However, few drugs show a statistically and clinically significant improvement in the outcomes leading to the Competent Authority approval. In this review we analyzed the European Medicines Agency breast cancer drug indications issued between January 2015 and June 2021 and we evaluated the clinical trials results leading to the approval and their update. AbstractBreast cancer represents the first cause of cancer worldwide and the leading cause of cancer mortality for women. Therefore, new therapies are needed to improve the prognosis of women diagnosed with this disease. In this review, we summarize the new drug indications for the treatment of breast cancer approved by European Medicines Agency between January 2015 and June 2021. In particular, we analyzed the clinical trials results leading to approvals and their update (when available), according to setting (localized and locally advanced or metastatic) and clinical features (hormone receptor positive, HER2 positive, triple negative, BRCA 1/2 mutation). The aim of this paper is to describe the clinical benefit obtained with the new indications.

BackgroundThe association between obesity and outcomes in patients receiving programmed death-1/programmed death ligand-1 (PD-L1) checkpoint inhibitors has already been confirmed in pre-treated non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 tumor expression.MethodsWe present the outcomes analysis according to baseline body mass index (BMI) and BMI variation in a large cohort of metastatic NSCLC patients with a PD-L1 expression ≥50%, receiving first line pembrolizumab. We also evaluated a control cohort of metastatic NSCLC patients treated with first line platinum-based chemotherapy. Normal weight was set as control group.Results962 patients and 426 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Obese patients had a significantly higher objective response rate (ORR) (OR=1.61 (95% CI: 1.04–2.50)) in the pembrolizumab cohort, while overweight patients had a significantly lower ORR (OR=0.59 (95% CI: 0.37–0.92)) within the chemotherapy cohort. Obese patients had a significantly longer progression-free survival (PFS) (HR=0.61 (95% CI: 0.45–0.82)) in the pembrolizumab cohort. Conversely, they had a significantly shorter PFS in the chemotherapy cohort (HR=1.27 (95% CI: 1.01–1.60)). Obese patients had a significantly longer overall survival (OS) within the pembrolizumab cohort (HR=0.70 (95% CI: 0.49–0.99)), while no significant differences according to baseline BMI were found in the chemotherapy cohort. BMI variation significantly affected ORR, PFS and OS in both the pembrolizumab and the chemotherapy cohorts.ConclusionsBaseline obesity is associated to significantly improved ORR, PFS and OS in metastatic NSCLC patients with a PD-L1 expression of ≥50%, receiving first line pembrolizumab, but not among patients treated with chemotherapy. BMI variation is also significantly related to clinical outcomes.

Background: The reasons behind low adherence to the Mediterranean diet (Med-diet) are still not entirely known. We aimed to evaluate the effect of biological (i.e., sex-related) and psycho-socio-cultural (i.e., gender-related) factors on Med-diet adherence. Methods: Baseline Med-diet adherence was measured using a self-administered questionnaire among adults with ischemic heart disease (IHD) from the EVA (Endocrine Vascular Disease Approach) study. A multivariable analysis was performed to estimate the effect of sex- and gender-related factors (i.e., identity, roles, relations, and institutionalized gender) on low adherence. Results: Among 366 participants (66 ± 11 years, 31% women), 81 (22%) adults with low adherence demonstrated higher rates of diabetes, no smoking habit, lower male BSRI (Bem Sex Role Inventory) (median (IQR) 4.8 (4.1 to 5.5) vs. 5.1 (4.5 to 5.6) and p = 0.048), and higher Perceived Stress Scale 10 items (PSS-10) (median (IQR) 19 (11 to 23) vs. 15 (11 to 20) and p = 0.07) scores than those with medium-high adherence. In the multivariable analysis, only active smoking (odds ratio, OR = 2.10, 95% confidence interval, CI 1.14 to 3.85 and p = 0.017), PPS-10 (OR = 1.04, 95% CI 1.00 to 1.08, and p = 0.038) and male BSRI scores (OR = 0.70, 95% CI 0.52 to 0.95, and p = 0.021) were independently associated with low adherence. Conclusions: Male personality traits and perceived stress (i.e., gender identity) were associated with low Med-diet adherence regardless of the sex, age, and comorbidities. Therefore, gender-sensitive interventions should be explored to improve adherence in IHD.

Background: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events. Patients and methods: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported. Results: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3–2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5–3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated (p = 0.009, p < 0.0001, p < 0.0001). Overall COVID-19 prevalence was 1.2% for vaccinated (six of 482 cases, all confirmed) and 1.7% for unvaccinated (8 of 473, 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference remained non-significant, considering confirmed COVID-19 only (p = 0.33). Conclusion: COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.