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Key Clinical Message: We report on the successful use of chemotherapy for treatment of stage 2B testicular seminoma in a carrier of the Leber's hereditary optic neuropathy 11778 mitochondrial mutation. Neurotoxic chemotherapy may not prompt disease conversion. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Phase 1 oncology trials provide access to new therapies and may improve cancer outcomes. Phase 1 trials conducted in the Asian‐Pacific region are increasing at a faster rate than the global trend. This study aimed to describe the changing landscape of phase 1 oncology trials in Australia in the last decade.This cross‐sectional study reviewed phase 1 oncology trials registered on ClinicalTrials.gov conducted in Australia. Phase 1 trials were included for analysis if they enrolled adults with solid organ malignancies, used at least one systemic agent, and were first registered between January 1, 2012, and December 31, 2022. The number of trials, site locations, sponsor type, and drug class were analyzed using descriptive statistics.Over the 10‐year period, ClinicalTrials.gov included 493 phase 1 clinical trials across 71 Australian sites. Most sites were in metropolitan locations; in Melbourne, trials were concentrated within selected sites, while in Sydney, trials were spread across a larger number of sites. The number of phase 1 trials per annum increased from 18 in 2012 to 75 in 2022. Since 2020, emerging biopharmaceutical companies have become the predominant sponsor type, a trend that is also seen globally. While most trial sponsors were North American (42%), there was increasing representation from Asian sponsors over the 10‐year period (6% in 2012 to 39% in 2022). Immunomodulatory (45%) and targeted approaches (44%) accounted for most drug classes used alone or in combination.There are an increasing number of phase 1 trials conducted within Australia. Sponsors of phase 1 trials are increasingly from Asian countries and are more likely to be emerging biopharmaceutical companies. [ABSTRACT FROM AUTHOR]

Background: Consolidation durvalumab after concurrent chemoradiation is the standard of care for unresectable stage III non‐small cell lung cancer (NSCLC) based on the PACIFIC trial. However, there have been reports in the literature suggesting the efficacy of the treatment differs in patients whose tumors harbor epidermal growth factor receptor (EGFR) mutations and in those with low programed death ligand‐1 (PD‐L1) expression. This study describes the survival outcomes for patients with unresectable stage III NSCLC treated with chemoradiation followed by durvalumab with a specific focus on EGFR mutation status and PD‐L1 expression. Methods: This retrospective observational study was conducted across six sites in Greater Sydney, Australia. It included all patients diagnosed with unresectable stage III NSCLC treated with chemoradiation and who received at least one cycle of durvalumab between January 2018 and September 2021. Patients were stratified according to EGFR mutation status and PD‐L1 tumor proportion score (TPS) of 1%. Results: Of the 145 patients included in the analysis, 15/145 (10%) patients harbored an EGFR mutation and 61/145 (42%) patients had PD‐L1 TPS of <1%. At a median follow‐up of 15.1 months from the start of durvalumab, median progression‐free survival (PFS) in EGFR mutant versus wild‐type patients was 7.5 and 33.9 months, respectively (hazard ratio [HR]: 2.7; 95% confidence intervals [95% CI] 1.2–5.7; p =.01). Overall survival (OS) was not different between EGFR mutant and wild‐type patients. There was no statistically significant difference in PFS (HR.7, 95% CI.4–1.7, p =.43) or OS (HR.5, 95% CI.4–4.7, p =.16) between patients with PD‐L1 TPS of <1% versus PD‐L1 TPS of ≥1%. Conclusions: Our data adds to the growing evidence that suggests consolidation durvalumab after definitive chemoradiation may not be as efficacious in patients with EGFR‐mutant tumors compared with EGFR wild‐type NSCLC. [ABSTRACT FROM AUTHOR]

Sustained elevation in neutrophil‐to‐lymphocyte ratio (NLR) after initial chemoradiotherapy (CRT) has been shown to correlate with worse prognosis in a number of solid organ malignancies. Here, we conducted a retrospective observational cohort study involving six sites across Sydney, Australia, including all patients with unresectable stage III NSCLC treated with CRT and consolidation durvalumab between January 2018 and September 2021. Patients had NLR collected prior to CRT and prior to cycle one of durvalumab. We used an NLR value of 3 to stratify patients into high and low groups. Patients with sustained NLR were defined as those with values ≥3 at both timepoints. A total of 145 patients were included in the study. The median age of patients was 66 years with median follow‐up of 15.1 months. The median PFS was 17.6 months in the pre‐CRT NLR high cohort and not reached (NR) in the pre‐CRT NLR low cohort (HR 1.99; p = 0.01). The median OS was 35.5 months in the high pre‐CRT NLR cohort compared with 42.0 months in the low pre‐CRT NLR cohort (HR 2.62; 95% CI: 1.23–5.56, p < 0.01). Median PFS for sustained NLR elevation was 17.1 months versus NR (HR 1.5; p < 0.01). Pre‐CRT NLR and sustained NLR remained independently prognostic for PFS on multivariate analysis (p = 0.04, p = 0.01) respectively. Pre‐CRT NLR and sustained NLR is associated with worse PFS outcomes in unresectable stage III NSCLC treated with CRT and durvalumab. Pre‐CRT NLR is also associated with worse OS. [ABSTRACT FROM AUTHOR]

Colorectal cancer remains the third most common malignancy in Australia with the peritoneum being the second most common metastatic site. Colorectal peritoneal carcinomatosis (CPC) can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy but this is only limited to a small subset of patients. Those with inoperable disease have a particularly poor prognosis. While the ideal systemic regimen has not been defined, 5‐fluorouracil‐based chemotherapy regimens appear to provide overall and progression free survival benefits. The role of targeted agents such as bevacizumab (vascular endothelial growth factor inhibitor) or cetuximab (epidermal growth factor inhibitor) in the setting of CPC is still evolving. Currently, retrospective analyses have shown promising results for the use of bevacizumab in addition to systemic chemotherapy but similar results have not been seen with cetuximab or panitumumab. However, there is significant heterogeneity in the trial data, lack of prospective randomized controlled trials and demonstrated treatment variability based on age and tumour characteristics. This review summarises the current literature in regard to treatment in the unresectable CPC setting as well as discussing issues with the current data and highlighting the need for further trials. [ABSTRACT FROM AUTHOR]

Background: Overall survival is the optimal marker of treatment efficacy in randomized clinical trials (RCTs) but can take considerable time to mature. Progression-free survival (PFS) has served as an early surrogate of overall survival but is imperfect. Time to deterioration in quality of life (QOL) measures could be a surrogate for overall survival., Methods: Phase 3 RCTs in solid malignancies that reported overall survival, PFS, and time to deterioration in QOL or physical function published between January 1, 2010, and June 30, 2022, were evaluated. Weighted regression analysis was used to assess the relationship between PFS, time to deterioration in QOL, and time to deterioration in physical function with overall survival. The coefficient of determination (R2) was used to quantify surrogacy., Results: In total, 138 phase 3 RCTs were included. Of these, 47 trials evaluated immune checkpoint inhibitors and 91 investigated non-immune checkpoint inhibitor agents. Time to deterioration in QOL (137 RCTs) and time to deterioration in physical function (75 RCTs) performed similarly to PFS as surrogates for overall survival (R2 = 0.18 vs R2 = 0.19 and R2 = 0.10 vs R2 = 0.09, respectively). For immune checkpoint inhibitor studies, time to deterioration in physical function had a higher association with overall survival than with PFS (R2 = 0.38 vs R2 = 0.19), and PFS and time to deterioration in physical function did not correlate with each other (R2 = 0). When time to deterioration in physical function and PFS are used together, the coefficient of determination increased (R2 = 0.57)., Conclusions: Time to deterioration in physical function appears to be an overall survival surrogate measure of particular importance for immune checkpoint inhibitor treatment efficacy. The combination of time to deterioration in physical function with PFS may enable better prediction of overall survival treatment benefit in RCTs of immune checkpoint inhibitors than either PFS or time to deterioration in physical function alone., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)