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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]

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 (R 2) 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 (R 2 = 0.18 vs R 2 = 0.19 and R 2 = 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 (R 2 = 0.38 vs R2 = 0.19), and PFS and time to deterioration in physical function did not correlate with each other (R 2 = 0). When time to deterioration in physical function and PFS are used together, the coefficient of determination increased (R 2 = 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. [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]

Growing teratoma syndrome (GTS) is rare and can mimic disease recurrence in patients with a history of immature teratoma. Benign hypermetabolic lymphadenopathy found on staging and surveillance computed tomography (CT) and positron emission tomography (PET) may lead to the presumption of metastatic malignancy. We report a case of a 38 year old with mixed mature and immature teratomas who developed new peritoneal masses after adjuvant chemotherapy despite a normalization of tumor markers. In addition to low FDG uptake observed in these peritoneal masses, a PET scan showed hypermetabolic lymphadenopathy and pulmonary and spleen lesions suggesting widespread metastases. Subsequent surgical resection confirmed a mixed pathology with GTS and sarcoidosis. We reviewed the current literature evidence of GTS and sarcoidosis as a benign cause of lymphadenopathy in cancer patients. We emphasize the importance of a tissue diagnosis before instituting therapy for presumed cancer recurrence to avoid potentially fatal diagnostic traps and management errors. A multiple disciplinary team approach is imperative in managing patients with suspected recurrent immature teratomas. [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]

Overall survival (OS) results from randomized control trials (RCT) provide the strongest evidence for efficacy of anti-cancer treatments but can take a considerable amount of time to mature. Progression free survival (PFS) and objective response rate (ORR) are used as an early surrogate of OS treatment effect however their validity remains unclear. Our study aims to comprehensively evaluate ORR and PFS as surrogates for OS treatment effect across tumor groups and treatment types. Phase 3 RCTs in solid malignancies that reported OS/PFS and ORR published between 1st of January 2010 and 30th of June 2022 were evaluated. The relationship of surrogate endpoints and OS treatment effect was assessed via weighted linear regression. The coefficient of determination (R2) quantified the fit of the regression model. 675 phase 3 RCT comprising of 350 112 patients were analysed. ORR (R2 of 0.10) and PFS (R2 of 0.38) were poor surrogate markers of OS treatment effect. The strength of surrogacy differed within treatment and tumour groups. PFS had the highest R2 for chemotherapy (0.56) and lowest for targeted therapy (0.40). PFS had the highest level of surrogacy for melanoma (R2 = 0.72) and pancreatic cancer (R2 = 0.70) compared to other tumour groups. Importantly ORR and PFS were also poorly correlated to each other (R2 = 0.33). ORR and PFS were poor trial-level surrogate markers of OS. The surrogacy performance of ORR and PFS differed by treatment and malignancy sub-type. • ORR and PFS are not strong surrogates of OS treatment effect. • Surrogacy of ORR and PFS for OS differs based on treatment and tumor. • surrogacy of ORR and PFS for OS treatment effect was highest for chemotherapy. • PFS was a better surrogate of OS treatment for melanoma and pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objective: Several predictors of survival have been identified in EGFR-positive non-small cell lung cancer (NSCLC) patients treated with first generation EGFR inhibitors. Prognostic models of survival outcomes with afatinib have not been evaluated. Methods: A prognostic tool for overall survival (OS)/progression free survival (PFS) based on pre-treatment clinicopathological factors was developed for EGFR-positive advanced NSCLC patients treated with first-line afatinib using penalised regression of individual-participant data from LUX-Lung 3 and 6 (n = 468). Favourable, intermediate and poor risk groups were identified and externally validated using LUX-Lung 1 (n = 390) and LUX-Lung 2 (n = 129) trials that initiated afatinib following previous chemotherapy or EGFR inhibitor treatment. Results: Discriminative performance was good in the development and validation cohorts. For patients treated with first-line afatinib, the median OS for the favourable, intermediate and poor risk groups were > 47.7, 29.3 and 16.4 months, respectively, and the median PFS were 17.3, 13.2 and 8.3 months, respectively. The improvement in median OS with afatinib use compared to chemotherapy was > 12.4 months for the favourable risk group, whereas no OS benefit was apparent for the poor risk group. The improvement in median PFS with afatinib use compared to chemotherapy was 10.2 months for the favourable risk group and 3.2 months for the poor risk group. Conclusions: A prognostic tool was developed and validated to identify favourable, intermediate and poor risk groups for OS/PFS in EGFR-positive advanced NSCLC patients treated with afatinib. The prognostic groups can inform the likely absolute OS/PFS benefit expected from afatinib compared to chemotherapy in first-line treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: To assess the sunprotection practices of undergraduates at the Australian National University. Methods: We sent emails with links to the questionnaire on the use of five sun-protection practices in the last fortnight of the summer to 3341 randomly selected students aged 18-24 years in this cross-sectional study. The response rate was 19% and 507 students met the inclusion criteria. Results: The sample consisted of 338 female and 169 male students with a mean age of 20.5 years (SD ± 1.9). Any method of sun protection was used always or often by 32% of respondents. The commonest method used was shade (58%) while the least common was wearing a hat (8%). Domestic students (44%) used sunglasses more than the international students (23%, P < 0.05) and female students used sunscreen (48%) and sunglasses (37%) more than male students (33% and 23% respectively) (P < 0.05). In the 22-24-year-old age group non-medical students (54%) used sunglasses more than the medical students (36%, P < 0.05). Conclusions: Only a third of the sample practiced any method of sun protection and there were significant differences in the practices between subgroups, suggesting they were at an increased risk of sun damage. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives It is uncertain whether survival increases from melanoma recorded by some population registries include a treatment effect. The US Surveillance, Epidemiology and End Results ( SEER) programme has good data quality control, large numbers of cases enabling high statistical precision and summary stage plus thickness, which we consider to be a best-case population registry scenario to investigate potential for a treatment effect. We have investigated SEER data to indicate whether survivals increases are fully attributable to earlier diagnosis and other non-treatment factors. Methods Through relative survival regression, the effects of diagnostic period on 5-year excess mortality were investigated, adjusting for socio-demographic factors, lesion sub-site, histology, thickness and stage at diagnosis in 1990-2009 (n = 99 690 cases). Results The reduction in excess mortality (95% confidence interval) between 1990-1999 and 2000-2009 was 31 (20-41)% for localised melanoma, 18 (12-22)% for regional melanoma and 3 (-5-10)% for melanomas with distant spread. Younger age was predictive of a greater percentage reduction. Treatment benefits are inferred from the higher survivals in 2000-2009 but uncertainty remains due to incomplete data to adjust for non-treatment factors and a lack of treatment data. Conclusions Registries should use new information systems to collect more complete data on stage, other prognostic indicators, co-morbidities and treatment, to provide more definitive and detailed information on population effects of cancer control. [ABSTRACT FROM AUTHOR]

Background: Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inconsistent cut point definitions, and minimal investigation of contemporary combination ICI therapy. Moreover, whether overweight and obese patients gain a larger benefit from contemporary frontline chemoimmunotherapy in non-small cell lung cancer (NSCLC) is unclear. Methods: This secondary analysis pooled individual patient data from the intention-to-treat population of the IMpower130 and IMpower150 RCTs comparing chemoimmunotherapy versus chemotherapy. Co-primary outcomes were overall survival (OS) and progression-free survival (PFS). The potentially non-linear relationship between BMI and chemoimmunotherapy treatment effect was evaluated using Multivariable Fractional Polynomial Interaction (MFPI). As a sensitivity analysis, chemoimmunotherapy treatment effect (chemoimmunotherapy versus chemotherapy) on survival was also estimated for each BMI subgroup defined by World Health Organisation classification. Exploratory analyses in the respective chemoimmunotherapy and chemotherapy cohort were undertaken to examine the survival outcomes among BMI subgroups. Results: A total of 1282 patients were included. From the MFPI analysis, BMI was not significantly associated with chemoimmunotherapy treatment effect with respect to either OS (p = 0.71) or PFS (p = 0.35). This was supported by the sensitivity analyses that demonstrated no significant treatment effect improvement in OS/PFS among overweight or obese patients compared to normal weight patients (OS: normal BMI HR = 0.74 95% CI 0.59–0.93, overweight HR = 0.78 95% CI 0.61–1.01, obese HR = 0.84 95% CI 0.59–1.20). Exploratory analyses further highlighted that survival outcomes were not significantly different across BMI subgroups in either the chemoimmunotherapy therapy cohort (Median OS: normal BMI 19.9 months, overweight 17.9 months, and obese 19.5 months, p = 0.7) or the chemotherapy cohort (Median OS: normal 14.1 months, overweight 15.9 months, and obese 16.7 months, p = 0.7). Conclusion: There was no association between high BMI (overweight or obese individuals) and enhanced chemoimmunotherapy treatment benefit in front-line treatment of advanced non-squamous NSCLC. This contrasts with previous publications that showed a superior treatment benefit in overweight and obese patients treated with immunotherapy given without chemotherapy. [ABSTRACT FROM AUTHOR]