Concomitant Drugs Prognostic Score in Patients With Metastatic Renal Cell Carcinoma Receiving Ipilimumab and Nivolumab in the Compassionate Use Program in Italy: Brief Communication.

A concomitant drug-based score was developed by our group and externally validated for prognostic and predictive purposes in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). The model considers the use of three classes of drugs within a month before initiating ICI, assigning score 1 for each between proton pump inhibitor and antibiotic administration until a month before immunotherapy initiation and score 2 in case of corticosteroid intake. In the present analysis, the drug score was validated in a prospective population of 305 patients with metastatic renal cell carcinoma treated with ipilimumab plus nivolumab in the first-line setting. The value of the model in predicting overall survival and progression-free survival was statistically significant and clinically meaningful, with an overall survival rate at 12 months of 73% vs. 44% (P<0.0001), and median progression-free survival of 11.6 (95% CI: 9.1-14.1) months versus 4.8 (95% CI: 2.7-7.0) months (P=0.002), respectively, for patients belonging to the favorable group (score 0-1) versus the unfavorable (score 2-4). Further development will be represented by the gut microbiome analysis according to the drug-based model classification and to the outcome of patients to ICI therapy to demonstrate the link between drug exposure and immune sensitivity.

COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study.

BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8-75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00-3·62), being a current or former smoker (4·24, 1·70-12·95), receiving treatment with chemotherapy alone (2·54, 1·09-6·11), and the presence of any comorbidities (2·65, 1·09-7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11-9·06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None.

Use of a natural multicomponent mouthwash plus oral hygiene vs oral hygiene alone to prevent everolimus-induced stomatitis: the STOP multicenter, randomized trial.

BACKGROUND: Stomatitis is highly prevalent in patients with cancer treated with the mammalian target of rapamycin inhibitor everolimus; it usually has an early onset and may compromise treatment dose intensity and patients' quality of life. Within the randomized controlled Stomatitis Prevention trial (STOP, ISRCTN14568888), we investigated the possibility of using a commercial natural multicomponent mouthwash (Orasol Plus®) to prevent the development of stomatitis of any grade in patients with advanced renal cell carcinoma (RCC) treated with everolimus. METHODS: Overall, 62 patients were randomized to receive either Orasol Plus in addition to oral hygiene or oral hygiene alone (31 patients per treatment arm). RESULTS: In the whole study population, 28 episodes of stomatitis were observed (41.9%); in only 2 patients, stomatitis occurred more than once (2 episodes). As expected, the episodes of stomatitis occurred early in the course of treatment with everolimus. Treatment with Orasol Plus prevented the onset of everolimus-induced stomatitis: only 8 episodes of stomatitis were observed in the treated group with Orasol Plus in addition to oral hygiene vs 20 episodes in the group treated with oral hygiene only (p = 0021). Also, a reduction in the average duration of mucositis in patients treated with Orasol Plus compared to patients treated with oral hygiene only was observed (8 days vs 11.2 days, p = 0.0416). CONCLUSION: This study showed that the use of a natural multicomponent mouthwash coupled with regular oral hygiene was able to reduce the severity and duration of everolimus-induced stomatitis in patients with RCC. TRIAL REGISTRATION NUMBER: ISRCTN14568888.

Cisplatin and gemcitabine in malignant pleural mesothelioma: a phase II study.

Aims of this study were to evaluate the activity and toxicity of gemcitabine and cisplatin combination in malignant pleural mesothelioma (MPM). Patients with histologically proven MPM, < 75 years of age, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2, and measurable MPM were eligible. Patients received gemcitabine 1250 mg/m intravenously on days 1 and 8 and cisplatin 75 mg/m on day 2, every 21 days, for a maximum of 6 cycles. From May 1999 to May 2001, 35 chemonaive patients (median age, 61 years) were enrolled. A total of 177 cycles were administered (median 5 cycles; range 1 to 6). One patient was not evaluable for response and toxicity. Nine (26%) patients had partial responses, 11 (32%) patients had progressive disease, and 14 (41%) stable disease. Median survival for all patients was 13 months. Median progression-free survival was 8 months. Grade 3 (World Health Organization) nausea and vomiting occurred in 35% of patients. Grade 3/4 anemia, grade 3/4 thrombocythemia, and grade 3/4 neutropenia were assessed in 24%, 52%, and 61% of patients, respectively. All other side effects were mild. In conclusion, gemcitabine-cisplatin combination seems to be moderately active in MPM. Furthermore, at this dose and schedule, the toxicity profile could be acceptable.

Single-agent gemcitabine in previously untreated elderly patients with advanced bladder carcinoma: response to treatment and correlation with the comprehensive geriatric assessment.

OBJECTIVE: The study aimed at evaluating the activity and toxicity of gemcitabine monochemotherapy in a unselected series of elderly patients with advanced bladder cancer. The secondary objectives were to establish whether there is a correlation between treatment and Comprehensive Geriatric Assessment (CGA) and, in addition, to determine overall patient survival. METHODS: Treatment consisted of six courses of chemotherapy with gemcitabine at a dosage of 1,200 mg/m2 on days 1 and 8, every 21 days. CGA, as described by Gruppo Italiano di Oncologia Geriatrica, was assessed for evaluating the functional status of patients before, during, and after treatment. RESULTS: Twenty-five patients were enrolled (M/F 22/3), 22 of these were evaluable for response and 23 for toxicity. Characteristics of patients: median age 76 years (range 71-87); ECOG performance status (PS) 1 in 12 patients and 2 in 13 patients; clinical stage III in 6 patients and IV in 19 patients. At the end of the therapy the parameters of CGA improved in 4 cases (17%), remained unchanged in 17 cases (74%) and worsened only in 2 cases (9%). Two patients were not evaluable. Response evaluation showed 3 (13.5%) complete responses (CRs) and 7 (32%) partial responses (PRs), for an overall response rate of 45.5% [95% confidence interval (CI), 24.3-65.7%]. Three (13.5%) patients had stable disease (SD ) and 9 (41%) disease progression (DP). Median overall survival was 8 months and median time to progression was 5 months. Treatment was generally well tolerated, with 1 patient having grade 3 gastrointestinal toxicity and 3 having grade 4 neutropenia. CONCLUSIONS: We conclude that gemcitabine can be safely administered in monochemotherapy, is effective and does not worsen the functional status of elderly patients with advanced bladder cancer.