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Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

High percentage of patients with luminal-like MBC received CT as first-line therapy in real-life. The choice was mainly driven by age and site of metastases. With the limitations of a non-randomized comparison, no differences on patients' outcome were observed depending on the first-line strategy.

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BackgroundMale breast cancer (MBC) is rare. Given the paucity of randomized trials, treatment is generally extrapolated from female breast cancer guidelines.MethodsThis is a retrospective analysis of all male patients presenting with MBC at the Department of Oncology at University Federico II of Naples between January 1989 and January 2014. We recorded the following data: baseline characteristics (age, height, weight, body mass index, risk factors, family history), tumor characteristics (side affected, stage, histotype, hormonal and HER2 status, and Ki-67 expression), treatment (type of surgery, chemotherapy, endocrine therapy, and/or radiotherapy), BRCA1/2 mutation status (if available), other tumors, and long-term survival.ResultsForty-seven patients were analyzed. Median age was 62.0 [55.0–72.0]. Among risk factors, obesity and family history of breast cancer were associated with 21 % and 30 % of MBC cases, respectively. The majority of tumors were diagnosed at an early stage: stage I (34.0 %) and stage II (44.7 %). Infiltrating ductal carcinoma was the most frequent histologic subtype (95.8 %). Hormone receptors were generally positive (88.4 % of cases were Estrogen receptor [ER] positive and 81.4 % Progesteron receptor [PgR] positive). Human epidermal growth factor receptor 2 (HER2) was positive in 26.8 % of cases; 7.0 % of MBCs were triple negative. The tumor had high proliferation index (Ki67 ≥ 20 %) in 64.7 %. Surgery was predominantly mastectomy (85.1 %), whereas quadrantectomy was performed in 14.9 % of patients. Adjuvant chemotherapy was administered to 70.7 % of patients, endocrine therapy to 90.2 %, trastuzumab to 16.7 % and radiotherapy to 32.6 %. BRCA status was available for 17 patients: 10 wild-type, 1 BRCA1 carrier, 5 BRCA2 carriers, 1 unknown variant sequence. The overall estimated long-term survival was about 90 % at 5 years, 80 % at 10 years and 70 % at 20 years. Patients carrying a BRCA mutation had a significantly lower survival than patients with wild-type BRCA (p = 0.04).ConclusionsLong-term survival was high in MBC patients referred to our clinical unit. Survival was poorer in BRCA-mutated patients than in patients with wild-type BRCA.

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Background: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods: A multicentre, single-arm, hypothesis-driven phase 2 trial was planned to study the effect of Tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints). A cohort of patients consecutively enrolled after phase 2 was used as a validation dataset. A multivariable logistic regression was performed to generate hypotheses, while controlling for possible confounders. Results: out of 301 patients in phase 2 intention-to-treat (ITT) analysis, 180 (59.8%) received tocilizumab. With 67 death events, lethality rates were 18.4% (97.5%CI: 13.6-24.0, P=0.52) and 22.4% (97.5%CI: 17.2-28.3, P<0.001) at 14 and 30 days. Lethality rates were lower in the validation dataset, including 920 patients. No signal of specific drug toxicity was reported. The multivariable logistic regression suggests tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Also, it supports a positive effect on lethality rate of the use of corticosteroids. Conclusions: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Such result support the use of tocilizumab while waiting for ongoing phase 3 trials.

Objective: The aim of this study was to analyze the long-term toxicity and quality of life (QOL) in patients with locally advanced cervical cancer (LACC) treated with chemoradiation [chemotherapy/radiotherapy (CT/RT)] or neoadjuvant CT (NACT) followed by radical surgery (RS). Methods: Fifty-nine patients with LACC in remission after treatment with NACT + RS (n = 34) or CT/RT (n = 25) were interviewed with an Incontinence Impact Questionnaire (IIQ-7), a Quality of Life Questionnaire (EORTC QLQ-C30), and a Quality of Life Questionnaire for Cervical Cancer (EORTC QLQ-CX24) to compare long-term toxicity and QOL. Results: The mean age was 53 ± 9.8 and 59 ± 11.5 years in the NACT + RS and CT/RT groups, respectively. Overall, diarrhea and constipation were reported in 15 and 68%, respectively, while bladder complaints and a low level of sexual enjoyment were reported in 36 and 47%, respectively. The NACT + RS patients showed a worse sexual activity (74.71 ± 33.57 vs. 92.06 ± 17.96; p = 0.019) and sexual enjoyment (71.21 ± 23.67 vs. 88.88 ± 21.71; p = 0.040) and more frequently complained of constipation (49.01 ± 34.06 vs. 26.66 ± 31.66; p = 0.013), while CT/RT patients more frequently suffered from diarrhea (1.96 ± 7.96 vs. 14.66 ± 28.40; p = 0.017). Conclusions: Many patients treated for LACC have long-term complaints regarding sexual activity and bladder and bowel function. The majority of QOL aspects were similar in the two groups at long-term follow-up. However, diarrhea was more frequent and severe in CT/RT patients, while constipation was more frequent and severe in NACT + RS patients, and they showed a worse sexual life perception. Larger randomized trials addressing these issues are needed.