ABSTRACT
Background Italy was heavily hit by the COVID-19 pandemic. According to official statistics, during 2020 there were more than 75,000 excess deaths compared to the average expected mortality in 2015-2019. General mortality (GM) is a good measure of both the direct and indirect effects of the pandemic because it's exempt from potential bias due to misclassification of events. Evidence shows a greater burden of disease and mortality attributable to COVID-19 among disadvantaged populations, with the risk of an exacerbation of existing health inequalities. We aim to analyse the trend of social inequalities in mortality during the first pandemic year in two Italian regions (Piedmont and Emilia-Romagna) using data from Administrative Population Registries (APR) and statistical databases. Methods Data on deaths occurred between Jan 2015 and Jan 2021 in subjects ≥65, stratified by educational level, were obtained from Regional APR and the Census. Using a time series approach, we computed Standardized Mortality Rates (SMR), Relative Index of Inequalities (RII) and Slope Index of Inequalities (SII), adjusted by age, gender, month and region. SMR, RII and SII from March 2020 were forecasted using Holt-Winters method and compared to the observed values in the same period. Results SMRs were higher than expected during the two 2020 epidemic waves (Mar-Apr, Oct-Dec) in both regions. RII didn't increase significantly. Absolute inequalities instead rose in Piedmont during both pandemic waves, mostly among women, and in Emilia-Romagna in March among men. Conclusions The impact of the pandemic on inequalities in GM has been at least of the same size of the impact of other mechanisms of unequal mortality. APR coupled with sociodemographic data are a quick and reliable source for assessing the unequal impact of the COVID-19 pandemic on health. Further research is needed to explore mechanisms underlying these effects e.g. inequalities in cause-specific mortality and access to health services. Key messages The unequal impact of the pandemic on mortality was confirmed. Administrative data linked with Census and health data are efficient and reliable sources for a timely monitoring of health inequalities.
ABSTRACT
Background: Pembrolizumab (pembro) is a PD-1 inhibitor indicated for the treatment (tx) of a several malignancies. Most clinical trials used a 3-weekly tx (Q3W) but a 6-weekly 400mg regimen (Q6W) is now approved, based on pharmacokinetic data, also supported by the KEYNOTE-555 trial. The real world tolerability of the Q6W remains unknown. The COVID-19 pandemic led to rapid adoption of the Q6W tx, usually in patients (pts) previously receiving Q3W tx, as it facilitates less hospital visits. We report the toxicity profile of pts treated with Q6W pembro and the comparison of the preceding Q3W tx. Methods: We retrospectively analysed adverse events for non-small cell lung cancer (NSCLC), urothelial cancer (UC) and melanoma pts, who received at least 1 cycle of Q6W pembro. Pts that received pembro in combination tx were excluded. Previous Q3W monotherapy was permitted. Toxicity was graded as per CTCAE v5.0. Results: We included 94 pts (melanoma=39, NSCLC=38, UC=17). Median number of Q6W cycles received was 3 (range 1-6). 71% received the Q3W regimen (median 7 cycles, range 1-32) prior to switching to Q6W. New toxicity of any severity was recorded in 52% (49/94) during Q6W versus 70% (47/67) during Q3W tx. G 3/4 toxicities occurred in 15% (15) during Q6W versus 0% during previous Q3W tx. Of the 27 who started de novo with Q6W, 4 (15%) developed G 3/4 toxicities. G 3/4 toxicities were: GI (4% [colitis = 2, gastritis =1, oral lichen planus = 1]), nephritis (3%), arthralgia (2%), skin (2%), myositis/CK rise (2%), anaemia (1%), myocarditis (1%). Steroids for management of toxicity were initiated in 22% (21) pts, including 8 with G2 toxicity. Three (3%) pts switched back to Q3W administration. None of them received Q6W again. In total 9% of pts in Q6W discontinued tx due to toxicity. Conclusions: In our cohort of pts, the majority were previously treated with the Q3W regimen without significant toxicity. Switch to Q6W or de novo Q6W pembro led to a 15% rate of G 3/4 toxicity and 9% discontinuation rate. In pts pre-treated with Q3W, we cannot distinguish whether this was due to cumulative toxicity or due to switch to Q6W. More studies are required to ascertain the safety of the Q6W schedule. In the COVID-19 context, any Q6W toxicity concern should be weighed against the advantages of fewer hospital visits. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.