Immune checkpoint inhibitor therapy for advanced cutaneous squamous cell carcinoma in Australia: a retrospective real world cohort study.

OBJECTIVES: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. STUDY DESIGN: Retrospective observational study; review of patient records in fifteen Australian institutions. SETTING, PARTICIPANTS: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. MAIN OUTCOME MEASURES: Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression-free survival. RESULTS: A total of 286 people with advanced CSCC received ICI therapy during May 2017 - May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3-97.5 years) and 232 were men (81%); median follow-up time was 12.2 months (interquartile range, 5.5-20.5 months). Eighty-eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve-month overall survival was 78% (95% confidence interval [CI], 72-83%); progression-free survival was 65% (95% CI, 58-70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0-4.3) and progression-free survival (aHR, 2.4; 95% CI, 1.8-3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1-3.0; progression-free: aHR, 1.8; 95% CI, 1.2-2.7). Fifty-five people (19%) reported immune-related adverse events of grade 2 or higher; there were no treatment-related deaths. CONCLUSION: In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials.

Developing technical support and strategic dialogue at the country level to achieve Primary Health Care-based health systems beyond the COVID-19 era.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Pursuing the objectives of the Declaration of Alma-Ata for Primary Health Care (PHC), the World Health Organization (WHO) and global health partners are supporting national authorities to improve governance to build resilient and integrated health systems, including recovery from public health stressors, through the long-term deployment of WHO country senior health policy advisers under the Universal Health Coverage Partnership (UHC Partnership). For over a decade, the UHC Partnership has progressively reinforced, via a flexible and bottom-up approach, the WHO's strategic and technical leadership on Universal Health Coverage, with more than 130 health policy advisers deployed in WHO Country and Regional Offices. This workforce has been described as a crucial asset by WHO Regional and Country Offices in the integration of health systems to enhance their resilience, enabling the WHO offices to strengthen their support of PHC and Universal Health Coverage to Ministries of Health and other national authorities as well as global health partners. Health policy advisers aim to build the technical capacities of national authorities, in order to lead health policy cycles and generate political commitment, evidence, and dialogue for policy-making processes, while creating synergies and harmonization between stakeholders. The policy dialogue at the country level has been instrumental in ensuring a whole-of-society and whole-of-government approach, beyond the health sector, through community engagement and multisectoral actions. Relying on the lessons learned during the 2014-2016 Ebola outbreak in West Africa and in fragile, conflict-affected, and vulnerable settings, health policy advisers played a key role during the COVID-19 pandemic to support countries in health systems response and early recovery. They brought together technical resources to contribute to the COVID-19 response and to ensure the continuity of essential health services, through a PHC approach in health emergencies. This policy and practice review, including from the following country experiences: Colombia, Islamic Republic of Iran, Lao PDR, South Sudan, Timor-Leste, and Ukraine, provides operational and inner perspectives on strategic and technical leadership provided by WHO to assist Member States in strengthening PHC and essential public health functions for resilient health systems. It aims to demonstrate and advise lessons and good practices for other countries in strengthening their health systems.