ABSTRACT
BACKGROUND: The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes. MATERIAL AND METHODS: Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05. RESULTS: Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor. DISCUSSION: Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.
Subject(s)
Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Carbolines , Heterocyclic Compounds, 4 or More Rings , Humans , Lung Neoplasms/pathology , Mesothelioma/drug therapy , Mesothelioma/pathology , Palliative Care , Tumor MicroenvironmentABSTRACT
Background: Few studies have explored the illness perceptions, experiences or attitudes towards the future of survivors of critical coronavirus disease 2019 (COVID-19). Through in-depth qualitative interviews, we aimed to enrich our understanding of participants' perspectives, with the hope of offering more holistic and appropriate care to future patients. Methods: Participants who had survived critical COVID-19 illness (defined as a laboratory or clinical diagnosis of COVID-19, with hypoxia requiring high-flow nasal oxygen (HFNO) or mechanical ventilation) were invited to participate. After informed consent procedures, clinic-demographic details were documented and individual interviews conducted using a topic guide, and were audio-recorded, translated, transcribed and coded into NVivo software where themes were extracted. Results: Of 21 participants (13 female, 8 male), the mean age was 51.8 years (range 34 - 68), and mean duration of COVID symptoms was 21.7 days (range 17 - 37). Eighteen participants had been on HFNO, and 5 required mechanical ventilation. The major themes were: distressing experience; faith-based beliefs sustaining them; gratitude to healthcare workers (HCWs); better understanding of COVID and how dangerous it is; optimism for the future; and a resolve to implement lifestyle changes. Conclusion: Qualitative interviews revealed our participants' experience of severe COVID-19 as a difficult and terrifying ordeal, mitigated by faith-based beliefs, and the presence and care of HCWs. These experiences were reported by the participants as life changing, and all were inspired to focus on future self-care, and invest in fulfilling relationships. These insights call for future interventions to improve patient-centred care, including follow-up debriefing sessions, and support for lifestyle changes.