Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial.

BACKGROUND: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score. PATIENTS AND METHODS: Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability. RESULTS: Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN. CONCLUSIONS: After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03141177.

Does vitamin D deficiency affect functional outcomes in hip fracture patients? A meta-analysis of cohort studies.

BACKGROUND: Vitamin D deficiency is common in patients with hip fractures and may negatively affect functional recovery and quality of life (QOL). OBJECTIVE: This study aimed to conduct a meta-analysis to quantify the effects of vitamin D deficiency on physical function and quality of life after hip fractures. METHODS: The PubMed, EMBASE, Scopus, and Cochrane Library databases were searched for relevant studies. The inclusion criteria were hip fracture, comparison between vitamin D deficiency and normal vitamin D levels in patients with hip fracture, and functional outcome as the primary outcome. The exclusion criteria were case reports, reviews, duplicates, studies with a high risk of bias, and non-comparable or missing data. Two independent reviewers selected studies, extracted data, assessed bias, and performed meta-analyses using the Review Manager. Heterogeneity and publication bias were also assessed. Two independent reviewers selected the studies, extracted data, and assessed the risk of bias. We performed a meta-analysis using Review Manager and assessed heterogeneity and publication bias. RESULTS: Seven studies with 1,972 patients were included. Vitamin D deficiency was defined as a 25(OH)D level < 20 ng/mL. There were no significant differences in the ability to walk (OR 0.68, 95% CI 0.31-1.53, I2 = 69%) or length of hospital stay (MD 2.27 days, 95% CI - 2.47 to 7.01, I2 = 93%) between patients with and without vitamin D deficiency. However, patients with vitamin D deficiency had significantly worse functional ability and quality of life (SMD - 1.50, 95% CI - 2.88 to - 0.12, I2 = 96%). CONCLUSIONS: Despite the limitations of this study, such as small sample size, heterogeneous outcome assessments, and variable vitamin D measurement techniques, the results demonstrated that screening for vitamin D status and optimizing levels through supplementation could facilitate rehabilitation, promote lifestyle changes, aid in the recovery of independence, and help reduce long-term burdens.

Influence of environmental enrichment on sexual behavior and the process of learning and memory in a rat model of autism with valproic acid.

Autism spectrum disorder (ASD) is a psychiatric disorder with severe behavioral consequences and no specific therapy. Its etiology is multifactorial, as it is caused by a complex interaction of genetic and environmental factors. In rats, prenatal exposure to the antiepileptic drug valproic acid (VPA) has been associated with an increased risk of autistic-like behaviors in offspring, including social behavior deficits, increased repetitive behaviors, and cognitive impairments. In addition, VPA-treated rats have shown altered sociosexual behaviors. However, the mechanisms underlying these alterations in reproductive processes in VPA-treated rats are not fully understood. Interestingly some abnormal behaviors in VPA autism models are improved by an enriched environment (EE). In the present study, we examined the effects of EE on memory performance and sexual behavior in male rats. We found that on postnatal day 90, EE reduced the time it took for both control and VPA-treated groups to find a hidden platform in the Morris water maze. On PND 100, prenatal exposure to VPA reduced total exploring time in object recognition tests. On PND 110, EE reduced mount and intromission latency and increased ejaculatory frequency in VPA-treated male rats. These results suggest that environmental stimuli significantly influence the onset of sexual behavior in VPA-treated male rats and that EE may be a potential tool for improving a variety of behavioral deficiencies in rodent models of autism.

The Impact of Hypoalbuminemia on Postoperative Complications in Patients Undergoing Shoulder Arthroplasty: A Meta-Analysis.

OBJECTIVES: The objective of this meta-analysis was to investigate the association between hypoalbuminemia and postoperative complications in patients undergoing shoulder arthroplasty. METHODS: This meta-analysis study was registered in PROSPERO (CRD42023442466) and adhered to the PRISMA guidelines. Studies focused on shoulder arthroplasty that compared hypoalbuminemia and normal albumin levels were included. A systematic literature search was conducted in PubMed, EMBASE, Scopus, and the Cochrane Collaboration database. Seven comparative studies were included, and odds ratios with a 95% confidence interval were calculated for the dichotomous variables. A fixed-effect model was used when there was no statistical evidence of heterogeneity, and a random-effect model was used when significant heterogeneity was observed. Review Manager 5.4 software was used for data analysis. RESULTS: The meta-analysis included a total of 20,290 patients from seven studies. Hypoalbuminemia was significantly associated with a higher risk of readmissions (OR 2.92, 95%CI 1.74 to 4.91), reoperations (OR 3.23, 95%CI 1.98 to 5.27), an increase in hospital stay duration (MD 1.59, 95%CI 0.86 to 2.32), and complications such as death (OR 5.75, 95% CI 2.98 to 11.08; studies = 4), thromboembolic events (OR 2.43, 95% CI 1.46 to 4.06; studies = 4), cardiac events (OR 2.78, 95% CI 1.07 to 7.24; studies = 3), pulmonary infections (OR 3.09, 95% CI 1.54 to 6.20; studies = 3), systemic infections (OR 2.19, 95% CI 1.51 to 3.16; studies = 3), and transfusions (OR 3.16, 95% CI 2.23 to 4.48; studies = 2). However, there was no significant association between hypoalbuminemia and renal complications, surgical site infections, urinary tract infections, wound problems, or cardiovascular events. CONCLUSION: This meta-analysis provides strong evidence that hypoalbuminemia is associated with a higher risk of postoperative complications in patients undergoing shoulder arthroplasty.

Meningitis posquirúrgica por Acinetobacter baumannii multirresistente. Actividad sinérgica in vivo de la asociación sulbactam/avibactam / Post-surgical meningitis due to multiresistant Acinetobacter baumannii. In vivo synergistic activity of the sulbactam/avibactam association

Acinetobacter baumannii (AB) es un bacilo gram negativo, no fermentador,con frecuencia oportunista, ubicuo en el medio ambiente, con capacidad para sobrevivir en condiciones medioambientales adversas promoviendo su persistencia y diseminación en diferentes áreas de un hospital. Ha sido relacionado con múltiples brotes de infecciones asociadas al cuidado de la salud como neumonía, bacteriemias, contaminación de heridas quirúrgicas o infecciones del tracto urinario, especialmente entre pacientes con comorbilidades graves, como aquellos que motivan el ingreso a unidades de cuidados intensivos (UCI). Las cepas más problemáticas son aquellas resistentes a los carbapenémicos, resistencia causada por enzimas de la clase de las oxacilinasas (bla OXA) cromosómicas o plasmídicas y más recientemente bla NDM-1. La aparición de estas cepas deja escasos antimicrobianos activos (colistin, minociclina, tigeciclina; amikacina) que son limitados en su eficacia y su uso se asocia con toxicidad. A esto se agrega, como en la paciente que se describe, que desarrolló una meningitis posquirúrgica, la limitada capacidad de difusión en el sistema nervioso central (SNC) de estas últimas opciones. Una de las alternativas terapéuticas, es buscar asociaciones como sulbactam/avibactam que mostraron una adecuada actividad sinérgica y bactericida en asilamientos resistentes a ampicilina/sulbactam en base a una significativa reducción de la CIM que permite administrar dosis habituales, con mejor tolerancia y lograr concentraciones terapéuticas en SNC. Se presenta una paciente que desarrolló una meningitis posquirúrgica debida a una cepa de AB multirresistente.

Acinetobacter baumannii (AB) is a non-fermenting gram-negative bacillus, largely opportunistic, ubiquitous in the environment, with the ability to survive in adverse environmental conditions, promoting its persistence and dissemination in different areas of the hospital. It has been implicated in many outbreaks of healthcare-associated infections such as pneumonia, bacteremia, surgical wounds contamination, or urinary tract infections, especially among patients with previous severe illnesses such as those requiring admission to intensive care units (ICU). The most problematic strains are those resistant to carbapenems, resistance caused by chromosomal or plasmid oxacillinase class (bla OXA), and more recently bla NDM-1. The appearance of these strains leaves few active antimicrobials (Colistin, Minocycline, Tigecycline; Amikacin) that are limited in their efficacy and toxic. To this we must add, as is the case of our patient who presented post-surgical meningitis, the limited diffusion capacity in the central nervous system (CNS) of these last options. One of the therapeutic alternatives is to search for synergistic associations such as sulbactam/avibactam that showed rapid synergistic and bactericidal activity in isolates resistant to ampicillin/sulbactam due to a significant reduction in its MIC, which allows us to administer usual, better tolerated doses that reach therapeutic concentrations in CNS. Here, we present a patient who developed a post-surgical meningitis due to multiresistant AB

Obesity Does Not Increase Risk for Mortality in Severe Sepsis Trauma Patients.

INTRODUCTION: The prevalence of obesity in the United States is up to 40% in adults. Obese patients with severe sepsis have a lower mortality rate compared with normal body mass index (BMI) patients. We hypothesized that trauma patients with severe sepsis and obese BMI will have a decreased mortality risk in comparison with normal BMI patients. METHODS: The Trauma Quality Improvement Program (2017) was queried for adult trauma patients with documented BMI and severe sepsis. Patients were grouped based on BMI: non-obese trauma patients (nOTP) BMI <30 kg/m2 and obese trauma patients (OTP) ≥30 kg/m2. A multivariable logistic regression model was used for analysis of mortality. RESULTS: From 1246 trauma patients with severe sepsis, 566 (42.4%) were nOTP and 680 (57.6%) were OTP. OTP had increased length of stay (LOS) (19 vs 21 days, P < .001), intensive care unit (ICU) LOS (13 vs 18 days, P < .001) and ventilator days (10 vs 11 days, P < .001). After adjusting for covariates, when compared to normal BMI patients, patients who were overweight (OR 1.11 CI .875-1.41 P = .390), obese (OR .797 CI .59-1.06 P = .126), severely obese (OR .926 CI .63-1.36 P = .696) and morbidly obese (OR 1.448 CI 1.01-2.07 P = .04) all had a similar associated risk for mortality compared to patients with normal BMI. CONCLUSION: In adult trauma patients with severe sepsis, this national analysis demonstrated OTP had increased LOS, ICU LOS, and ventilator days compared to nOTP. However, patients with increasing degrees of obesity had similar associated risk of mortality compared to trauma patients with severe sepsis and a normal BMI.

Final results of the global and Asia cohorts of KAMILLA, a phase IIIB safety trial of trastuzumab emtansine in patients with HER2-positive advanced breast cancer.

BACKGROUND: KAMILLA is a single-arm safety study of trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC; NCT01702571). We report the final analysis of cohort 2 (Asia) within the context of published cohort 1 (Global) findings. METHODS: Patients had HER2-positive, locally advanced, or metastatic BC progressing after chemotherapy and anti-HER2 therapy or ≤6 months after adjuvant therapy. The primary objective was to further evaluate T-DM1 (3.6 mg/kg, administered intravenously every 3 weeks) safety/tolerability, including the following adverse events of primary interest (AEPIs): grade ≥3 AEPIs (hepatic events, allergic reactions, thrombocytopenia, hemorrhage events), all grade ≥3 treatment-related AEs, and all-grade pneumonitis. RESULTS: KAMILLA enrolled 2185 patients (cohort 1, n = 2003; cohort 2, n = 182) as of 31 July 2019. Of these, 2002 and 181 per cohort were treated and included in the safety population. Approximately 70% of patients had two or more previous treatment lines in the metastatic setting. Median T-DM1 exposure was 5.6 and 5.0 months per cohort; median follow-up was 20.6 and 15.1 months. The overall AEPI rate was higher in cohort 2 (93/181; 51.4%) versus cohort 1 (462/2002; 23.1%), mostly driven by a higher grade ≥3 thrombocytopenia rate in cohort 2. In cohort 2, grade ≥3 thrombocytopenia was not associated with grade ≥3 hemorrhagic events and most (128/138) fully resolved. Grade ≥3 treatment-related AEPI rates were 18.4% (cohort 1) and 48.6% (cohort 2), the latter mainly due to thrombocytopenia. Any-grade pneumonitis rates were 1.0% and 2.2%. No new safety signals were identified. Median (95% confidence interval) progression-free survival was 6.8 months (5.8-7.6 months) and 5.7 months (5.5-7.0 months) in cohorts 1 and 2, respectively; median overall survival was 27.2 months (25.5-28.7 months) and 29.5 months (21.1 months to non-estimable). In both cohorts, median progression-free survival and overall survival decreased with increasing prior therapy lines. CONCLUSIONS: Cohort 2 results aligned with previous findings in Asian patients, supporting the manageable safety profile and use of T-DM1 in advanced BC.

Calidad de vida relacionada con la salud en trabajadores de unidades de cuidados intensivos / Health-related quality of life among intensive care unit workers

Objetivo Analizar la calidad de vida relacionada con la salud en una muestra de médicos y enfermeras de 2 unidades de cuidados intensivos de la Ciudad Autónoma de Buenos Aires, Argentina. Método Estudio analítico, transversal y cuantitativo. Se utilizó el cuestionario SF-36 en su versión en español, el cual está compuesto por 8 dimensiones agrupadas en 2 componentes (físico y mental). Evalúa el estado de salud de los encuestados en una escala que va de 0 a 100, donde una mayor puntuación indica una mejor percepción del estado de la salud. Resultados Participaron 95 profesionales de 2 unidades de cuidados intensivos, siendo de una institución privada el 58% y de una institución pública el resto. La mayoría fueron mujeres (57%), médicos (37%), con una edad media de 42 años y con título máximo de pregrado y grado (59%). De las dimensiones que componen la calidad de vida relacionada con la salud, la de vitalidad fue la peor percibida, con una media de 53,3, y la función física fue la mejor evaluada, con 87,8. Las dimensiones que conforman el componente físico presentaron una mejor evaluación frente a las del componente mental. Las variables sexo (hombre), edad (>40 años), presencia de enfermedades crónicas, titulación (médico), carga horaria de trabajo (>40h semanales) y antigüedad laboral (>11 años) parecen influir negativamente sobre la percepción de la calidad de vida relacionada con la salud. Conclusiones Es necesario implementar estrategias tendientes a reducir el impacto de la actividad laboral sobre la salud psíquica y física de los profesionales de la salud, estableciendo estrategias de promoción de la salud y prevención de los riesgos psicosociales y ergonómicos conocidos, y adecuando las cargas y la duración de las jornadas de trabajo para preservar la integridad del trabajador de la salud. (AU)

Objective To analyse health-related quality of life in a sample of doctors and nurses from 2 intensive care units in the city of Buenos Aires, Argentina. MethodAn analytical, cross-sectional and quantitative study. The Spanish version of the SF-36 questionnaire was used, which comprises 8 dimensions grouped into 2 components (physical and mental) and evaluates the health status of respondents on a scale from 0 to 100; the higher the score, the better the perception of health status. Results Ninety-five professionals from 2 intensive care units participated, 58% from a private institution and the rest from a public institution. The majority were women (57%), doctors (37%) with an average age of 42 years and with a maximum undergraduate degree and degree (59%). Of the dimensions making up health-related quality of life, the vitality dimension was perceived poorest with an average of 53.3, and physical function was the best evaluated at 87.8. The physical component dimensions were better evaluated than those of the mental component. The variables sex (male), age (>40 years), presence of chronic diseases, qualification (medical), hourly workload (>40h per week) and years of service (>11 years), seem to have a negative influence on the perception of health-related quality of life. Conclusions Strategies need to be implemented to reduce the impact of work activity on the mental and physical health of health professionals. Strategies for health promotion and the prevention of known psychosocial and ergonomic risks are required, and workloads and duration of working hours need to be adjusted to preserve the integrity of health workers. (AU)

Health-related quality of life among intensive care unit workers.

OBJECTIVE: To analyse health-related quality of life in a sample of doctors and nurses from 2 intensive care units in the city of Buenos Aires, Argentina. METHODS: An analytical, cross-sectional and quantitative study. The Spanish version of the SF-36 questionnaire was used, which comprises 8 dimensions grouped into 2 components (physical and mental) and evaluates the health status of respondents on a scale from 0 to 100; the higher the score, the better the perception of health status. RESULTS: Ninety-five professionals from 2 intensive care units participated, 58% from a private institution and the rest from a public institution. The majority were women (57%), doctors (37%) with an average age of 42 years and with a maximum undergraduate degree and degree (59%). Of the dimensions making up health-related quality of life, the vitality dimension was perceived poorest with an average of 53.3, and physical function was the best evaluated at 87.8. The physical component dimensions were better evaluated than those of the mental component. The variables sex (male), age (> 40 years), presence of chronic diseases, qualification (medical), hourly workload (> 40 h per week) and years of service (> 11 years), seem to have a negative influence on the perception of health-related quality of life. CONCLUSIONS: Strategies need to be implemented to reduce the impact of work activity on the mental and physical health of health professionals. Strategies for health promotion and the prevention of known psychosocial and ergonomic risks are required, and workloads and duration of working hours need to be adjusted to preserve the integrity of health workers.

Behavioral consequences of postnatal undernutrition and enriched environment during later life.

In rat models, large litter groups during suckling are used in the study of undernutrition. Large litter sizes are known to promote alterations in memory processes and anxiety-like behavior. Nevertheless, the effect of large litter size on sexual behavior and the reproductive system is still unknown. Environmental enrichment has been reported to (EE) enhance behavior and to correct some of the alterations produced by postnatal undernutrition. We used the Elevated Plus Maze (EPN), Morris Water Maze (MWM), Object Recognition test (OR) and several parameters of sexual behavior to determine the effect of large litter size on rats exposed to enriched and non-enriched environments. Newborn Wistar rats of both sexes were assigned to be suckled under lactation conditions, in litters of 8 pups or 16 pups. The large litter size (16 pups) caused a reduction in weight gain during the lactation period. On PND 45, four experimental groups were established for both sexes: Well-nourished Non-enriched (WN); Well-nourished Enriched (WE); undernourished Non-enriched (UN); Undernourished Enriched (UE). On PND 90, the UN males spent more time in the open arms on EPM. On PND 100, the UE females increased the latency to find the platform in training days (D1-4) in MWM. On probe day (D5) the UE males spent more time in the target quadrants in MWM. On PND 110, irrespective of EE the large litter size had increased the exploration time in both groups (UN) and (UE) in OR test. On PND 120, the performance of sexual behavior was more evident by effect of EE irrespective of the litter size. In conclusion, the large litter size showed no effects on sexual behavior, in contrast, EE has a sharp influence on sexual behavior. Conversely, memory processes and anxiety-like behavior are altered by large litter size.

First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis.

BACKGROUND: Guidelines recommend atezolizumab plus nab-paclitaxel (A + nP) for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer expressing programmed death-ligand 1 (PD-L1) on tumor-infiltrating immune cells (IC), based on IMpassion130. We report the final overall survival (OS) and safety of that study as per the prespecified analysis plan. PATIENTS AND METHODS: Patients were randomized to nP 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) with atezolizumab 840 mg (A + nP) or placebo (P + nP; days 1 and 15), until progression or unacceptable toxicity. Coprimary endpoints were progression-free survival [intention-to-treat (ITT) and PD-L1 IC-positive populations] and OS (tested hierarchically in the ITT population and, if significant, in the PD-L1 IC-positive population). RESULTS: Each arm comprised 451 patients; 666 (73.8%) had died by the final OS analysis cut-off (median follow-up, 18.8 months; interquartile range, 8.9-34.7 months). Median OS in the ITT population was 21.0 months [95% confidence interval (CI), 19.0-23.4 months] with A + nP, and 18.7 months (95% CI, 16.9-20.8 months) with P + nP [stratified hazard ratio (HR), 0.87; 95% CI, 0.75-1.02; P = 0.077]. Exploratory analysis in the PD-L1 IC-positive population showed a median OS of 25.4 months (95% CI, 19.6-30.7 months) with A + nP (n = 185) and 17.9 months (95% CI, 13.6-20.3 months) with P + nP (n = 184; stratified HR, 0.67; 95% CI, 0.53-0.86). Safety outcomes were consistent with previous analyses and the known toxicity profiles of each agent. Immune-mediated adverse events of special interest were reported in 58.7% and 41.6% of patients treated with A + nP and P + nP, respectively. CONCLUSION: Although the OS benefit in the ITT population was not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed with A + nP in PD-L1 IC-positive patients, consistent with prior interim analyses. This combination remained safe and tolerable with longer follow-up.

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer.

BACKGROUND: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. PATIENTS AND METHODS: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. RESULTS: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. CONCLUSION: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.