First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study.

BACKGROUND: Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy. METHODS: This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786. FINDINGS: Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4-11·9] vs 9·2 months [5·9-11·2]; stratified hazard ratio 0·78 [0·63-0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3-29·4) with atezolizumab compared with 12% (6·7-18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3-4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]). INTERPRETATION: First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy. FUNDING: F Hoffmann-La Roche and Genentech Inc, a member of the Roche group.

Creating a community coalition to address violence.

Building a community-wide coalition to address violence evolved out of a five-year federally funded project on abuse during pregnancy. The setting for this coalition building is Haverhill, Massachusetts, a city of about 60,000, located northeast of Boston in the Merrimack River Valley. For nearly eight years, representatives of more than 30 agencies and institutions have been meeting monthly and creating programs and strategies to address violence in homes, schools, and neighborhoods, and designing interventions for children witnessing this violence. The purpose of this article is to describe the process of coalition building and provide an analysis of this work.

Effect of smoking, alcohol, and depression on the quality of life of head and neck cancer patients.

This pilot study examined the relationship between smoking, alcohol intake, depressive symptoms and quality of life (QoL) in head and neck cancer patients. A questionnaire on smoking, alcohol, depressive symptoms and QoL was distributed to head and neck cancer patients (N=81). Over one-third (35%) of the respondents had smoked within the last 6 months, 46% had drunk alcohol within the last 6 months and 44% screened positive for significant depressive symptoms. About one-third (32%) of smokers were interested in smoking cessation services and 37% of patients with depressive symptoms were interested in depression services. However, only 9% of those who drank alcohol expressed interest in alcohol services. Smoking was negatively associated with five scales of the SF-36V including Physical Functioning, General Health, Vitality, Social Functioning, and Role-Emotional Health. Depressive symptoms were negatively associated with all eight scales on the SF-36V and all four scales of the Head and Neck Quality of Life instrument. Surprisingly, alcohol was not found to be associated with any of the QoL scales. While smoking, alcohol intake and depression may be episodically treated, standardized protocols and aggressive intervention strategies for systematically addressing these highly prevalent disorders are needed in this population.