Subgroup analyses in randomized phase III trials of systemic treatments in patients with advanced solid tumours: a systematic review of trials published between 2017 and 2020.

BACKGROUND: Subgroup analyses of randomized controlled trials are very common in oncology; nevertheless, the methodological approach has not been systematically evaluated. The present analysis was conducted with the aim of describing the prevalence and methodological characteristics of the subgroup analyses in randomized controlled trials in patients with advanced cancer. METHODS: A systematic literature search using PubMed was carried out to identify all phase III randomized controlled trials conducted in adult patients affected by locally advanced or metastatic solid tumours, published between 2017 and 2020. RESULTS: Overall, 253 publications were identified. Subgroup analyses were reported in 217 (86%) publications. A statistically significant association of presence of subgroup analysis with study sponsor was observed: subgroup analyses were reported in 157 (94%) for-profit trials compared with 60 (70%) non-profit trials (P < 0.001). Description of the methodology of subgroup analysis was completely lacking in 82 trials (38%), only cited without methodological details in 100 trials (46%) and fully described in 35 trials (16%). Forest plot of subgroup analyses for the primary endpoint was available in 195 publications (77%). Among publications with reported forest plots, the median number of subgroups for primary endpoint was 19 (range 6-78). Out of the 217 publications with subgroup analyses, authors discuss the heterogeneity of treatment effect among different subgroups in 173 publications (80%), although a formal test for interaction for subgroup analysis of primary endpoint was reported for at least one variable only in 60 publications (28%). Correction for multiplicity was explicitly carried out only in nine trials (4%). CONCLUSIONS: The very high prevalence of subgroup analyses in published papers, together with their methodological weaknesses, makes advisable an adequate education about their correct presentation and correct reading. More attention about proper planning and conduction of subgroup analysis should be paid not only by readers, but also by authors, journal editors and reviewers.

Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario.

INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.