In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.
Several studies have shown that symptomatic toxicities associated with anti-cancer treatments, such as nausea and vomiting, are frequently under-reported by health care providers, even when prospectively collected within clinical trials. Such under-reporting can produce underestimation of the absolute rate of toxicity, which is highly relevant information for patients and their physicians in clinical practice, as well as for regulatory authorities. Systematic collection of patient-reported outcomes (PROs) has been demonstrated to be a valid, reliable, feasible, and more precise approach to tabulating symptomatic toxicities, compared to health care provider reporting. The U.S. NationalCancer Institute has developed a PRO version of the Common Terminology Criteria for Adverse Events (the "PRO-CTCAE") to improve toxicity measurement in clinical trials. The PRO-CTCAE is an item bank with 124 individually validated toxicity questions for patients, with an accompanying software system for directly collecting information about symptomatic adverse events from patients. The barriers and challenges that need to be addressed when considering broad integration of PRO toxicity monitoring in cancer clinical trials are discussed, including challenges related to data collection logistics, analytic approaches, and resource utilization. The advent of instruments like the PRO-CTCAE, conceived to describe therapy side effects from the patient perspective, brings the potential both to improve the quality of data for risk-benefit evaluation in clinical research, and to provide future patients facing treatment decisions with information about prior experiences of their peers.3
Docetaxel (75 mg m À2 3-weekly) is standard second-line treatment in advanced non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a weekly schedule (33.3 mg m À2 for 6 weeks) improved quality of life (QoL), a phase III study was performed with 220 advanced NSCLC patients, p75 years, ECOG PS p2. QoL was assessed by EORTC questionnaires and the Daily Diary Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough and hair loss significantly favoured the weekly schedule, while diarrhoea was worse. DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week, while nausea and loss of appetite were more severe in the weekly arm in the third week. Response rate and survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI 0.77 -1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia, febrile neutropenia and hair loss; any grade 3 -4 haematologic toxicity was significantly more frequent in the standard arm (25 vs 6%). The weekly schedule could be preferred for patients candidate to receive docetaxel as second-line treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and no evidence of strikingly different effect on survival.
Doublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent.
Detection of CMCs in peripheral blood samples at the time of MM diagnosis by semiquantitative RT-PCR does not add any significant predictive value to the stage of disease. Thus, this approach should not be used in clinical practice, and further studies are required to determine its usefulness.
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).
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