BACKGROUND/AIM:Early phase clinical trials (EPCTs) assess the tolerability of novel anti-cancer therapeutics in patients with advanced malignancy. Patient selection is important given the modest clinical benefit and time commitments for trials. Prognostic scores have been developed to facilitate identification of high-risk patients. This study aimed to compare five prognostic scores to predict survival for patients on an EPCT.PATIENTS AND METHODS:We performed a retrospective review of patients enrolled in EPCT at Liverpool Hospital, Sydney, from 2013 to 2023. Demographic, biochemical, and survival data were collected from electronic medical records. The score from five prognostic scoring systems (Royal Marsden hospital, MD Anderson Cancer centre, Gustave Roussy Immune, MD Anderson Immune Checkpoint Inhibitor and Princess Margaret Hospital Index) were calculated. Overall survival was measured using the Kaplan-Meier method and predictive discrimination was assessed using Harrell's c-index.RESULTS:A total of 218 patients across 36 EPCTs were included. The median overall survival was 9.8 months with 22% of patients dying in less than 90 days. Seventeen to thirty-four percent of patients were categorised as high-risk. The MDACC score obtained the highest predictability for overall survival for the whole cohort (c-index=0.67, 95%CI=0.62-0.72) and the immunotherapy-based cohort (c-index= 0.65, 95%CI=0.59-0.71). However, all scores performed similarly with a significant overlap in the confidence intervals.CONCLUSION:Our retrospective audit confirms the utility of prognostic scores to predict survival in an Australian EPCT cohort, with similar predictive discrimination across various scoring systems. Integration of these prognostic tools into EPCT screening processes may optimise benefits and reduce risks associated with EPCTs.

Older patients are often excluded from clinical trials with the majority of patients being between the ages of 18 and 64 [ [1] Shenoy P. Harugeri A. Elderly patients' participation in clinical trials. Perspect Clin Res. 2015; 6: 184-189 Crossref PubMed Google Scholar ]. This may be due to increased incidence of medical comorbidities in the older adults as well as poorer performance status, but often this is a result of clinical selection bias for suitability for clinical trials [ [1] Shenoy P. Harugeri A. Elderly patients' participation in clinical trials. Perspect Clin Res. 2015; 6: 184-189 Crossref PubMed Google Scholar , [2] Habr D. McRoy L. Papadimitrakopoulou V.A. Age is just a number: considerations for older adults in Cancer clinical trials. J Natl Cancer Inst. 2021; 113: 1460-1464 Crossref PubMed Scopus (20) Google Scholar ]. Early phase clinical trials (EPCTs) aim to assess the tolerability and toxicity profile of novel anti-cancer therapeutics. The primary goal is to determine dose limiting toxicity (DLT) in order to move forward within the drug development timeline. As a result, EPCTs are generally demanding trials for patients, with greater time commitments, more uncertainties regarding toxicities, and limited knowledge of therapeutic potential. Often patients who enrol into EPCTs have exhausted all standard of care options, and whilst EPCTs provide potential for tumour control, this may be at the cost of potentially unexpected toxicities. The survival outcomes of patients undergoing EPCTs have continued to improve over the past decade and the clinical benefit rate has reached almost 50% in some real-world data sets [ [3] Menon S. Davies A. Frentzas S. Hawkins C.A. Segelov E. Day D. et al. Recruitment, outcomes, and toxicity trends in phase I oncology trials: six-year experience in a large institution. Cancer Rep (Hoboken). 2022; 5e1465 Google Scholar ]. Age is not a typical exclusion criterion for enrolment into EPCTs with most protocols relying on Eastern Cooperative Group performance status (ECOG PS) scores and expected survival of over three months as the minimum criteria for recruitment. However, there is limited data exploring the outcomes of older adult patients who enrol into EPCTs. We conducted a 10-year retrospective clinical audit of all patients treated at the Liverpool Hospital Early Phase Trials Unit and explored the role of age as a determining factor for clinical outcomes.

Introduction: Early phase clinical trials (EPCTs) enable access to novel therapies for patients who have exhausted standard of care treatment and contribute a crucial role in drug development and research. Culturally and linguistically diverse (CALD) or socially disadvantaged patients have notably lower rates of participation in these trials. We aimed to characterise the social and cultural demographics of patients enrolled on an EPCT in South Western Sydney. Methods: We conducted a 10-year retrospective review of patients enrolled on a EPCT at Liverpool Hospital. CALD patients were defined as those born overseas or whose preferred language was other than English. The patient residential address was used to calculate distance travelled, and the Index of Relative Socioeconomic Disadvantage (IRSD) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) scores were calculated and used as a surrogate for socioeconomic status (SES). Results: Our study included 233 patients across 39 EPCTs. Ninety-one patients (39%) were identified as CALD. The median IRSD and IRSAD scores were 941 and 944, respectively, with 62.7-67.4% of patients residing in an area with greater disadvantage compared to the median of Australia. The median distance travelled was 17 kilometres with only 12% of participants travelling more than 50 km. CALD patients were more likely to reside in an area of low SES (OR 3.4, 95% CI: 1.8-6.5, p < 0.01) and travelled shorter median distances (10 vs. 23 km) when compared to non-CALD patients. Conclusion: Our study cohort contained a lower proportion of CALD patients and a higher SES than what we might have expected from our local population. Furthermore, there was a trend toward greater SES disadvantage (lower IRSD/IRSAD scores) for the CALD population. This study provides novel Australian data to support the underrepresentation of culturally diverse or disadvantaged patients on EPCTs. Future efforts should be made to reduce barriers to participation and improve equity in clinical trial participation.

Introduction: Treatment of oesophageal (OC), gastro-oesophageal junction (GOJ), and gastric cancer (GC) includes either neoadjuvant Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) for OC or GOJ or perioperative 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for OC, GOJ, and GC adenocarcinomas. This study aims to describe the real-world outcomes of patients with GC, GOJ, and OC treated with FLOT or CROSS and identify variables associated with efficacy through exploratory analysis. We also aimed to evaluate the comparison of FLOT and CROSS for the treatment of OC and GOJ adenocarcinomas. Methods: This is a retrospective observational study of patients with locally advanced OC, GOJ, or GC treated with FLOT or CROSS between January 2015 and June 2021 in 5 cancer centres across Sydney, Australia. Long-rank test was used to compare survival estimated between subgroups. Hazard ratios for univariate and multivariate analyses were estimated with Cox proportional regression. Results: The study included 168 patients. The 24-month relapse-free survival (RFS) and overall survival (OS) for FLOT were 59% and 69%, respectively. The median RFS was 29.6 months and median OS was not reached. For CROSS, the 24-month RFS and OS were 55% and 63% with a median RFS and OS of 28.5 and 40.2 months, respectively. There was no difference in OS and RFS between the treatments. FLOT was less tolerable than CROSS with more dose reductions, treatment discontinuation, and clinically relevant grade 3 and 4 toxicity. Neutrophil lymphocyte ratio was associated with survival for both treatments. Conclusion: Similar efficacy outcomes were seen in this real-world population compared to the clinical trials for FLOT and CROSS.

Background Neoadjuvant carboplatin and paclitaxel with radiotherapy (CROSS) and perioperative docetaxel, oxaliplatin, calcium folinate and fluorouracil (FLOT) are widely used for gastric (GC), gastro-oesophageal junction (GOJ) and oesophageal cancers (OC). Prognostic and predictive markers for response and survival outcomes are lacking. This study evaluates dynamic neutrophil-lymphocyte ratios (NLR), platelet-lymphocyte ratios (PLR), albumin and body mass index (BMI) as predictors of survival, response and toxicity. Methods This multi-centre retrospective observational study across 5 Sydney hospitals included patients receiving CROSS or FLOT from 2015 to 2021. Haematological results and BMI were recorded at baseline and pre-operatively, and after adjuvant treatment for FLOT. Toxicities were also recorded. An NLR ≥2 and PLR ≥200 was used to stratify patients. Univariate and multivariate analyses were performed to determine predictors of overall survival (OS), disease free survival (DFS), rates of pathological complete response (pCR) and toxicity. Results One hundred sixty-eight patients were included (95 FLOT, 73 FLOT). A baseline NLR ≥2 was predictive for worse DFS (HR 2.78, 95% CI: 1.41–5.50, P<0.01) and OS (HR 2.90, 95% CI: 1.48–5.67, P<0.01). Sustained elevation in NLR was predictive for DFS (HR 1.54, 95% CI: 1.08–2.17, P=0.01) and OS (HR 1.65, 95% CI: 1.17–2.33, P<0.01). An NLR ≥2 correlated with worse pCR rates (16% for NLR ≥2, 48% for NLR <2, P=0.04). A baseline serum albumin <33 was predictive of worse DFS and OS with a HR of 6.17 (P=0.01) and 4.66 (P=0.01) respectively. Baseline PLR, BMI, and dynamic changes in these markers were not associated with DFS, OS or pCR rates. There was no association of the aforementioned variables with toxicity. Conclusions This demonstrates that a high inflammatory state represented by an NLR ≥2, both at baseline and sustained, is prognostic and predictive of response in patients receiving FLOT or CROSS. Baseline hypoalbuminaemia is predictive of poorer outcomes.

INTRODUCTIONFluoropyrimidine and oxaliplatin-based adjuvant chemotherapy delivered as 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), or capecitabine and oxaliplatin (CAPOX) is the standard of care for resected stage III colon cancer. Without randomized trial data, we compared real-world dose intensity, survival outcomes, and tolerability of these regimens.METHODSRecords of patients treated with FOLFOX or CAPOX in the adjuvant setting for stage III colon cancer across four institutions in Sydney during 2006-2016 were reviewed. The relative dose intensity (RDI) of fluoropyrimidine and oxaliplatin of each regimen, disease-free survival (DFS), overall survival (OS), and incidence of grade ≥2 toxicities were compared.RESULTSCharacteristics of patients receiving FOLFOX (n = 195) and CAPOX (n = 62) were evenly matched. FOLFOX patients had a higher mean RDI for both fluoropyrimidine (85% vs. 78%, p < 0.01) and oxaliplatin (72% vs. 66%, p = 0.06). In spite of a lower RDI, CAPOX patients trended toward a better 5-year DFS (84% vs. 78%, HR = 0.53, p = 0.068) and similar OS (89% vs. 89%, HR = 0.53, p = 0.21) compared to the FOLFOX group. This difference was most pronounced in the high-risk (T4 or N2) group where 5-year DFS was 78% versus 67% (HR = 0.41, p = 0.042). Patients receiving CAPOX experienced more grade ≥2 diarrhea (p = 0.017) and hand-foot syndrome (p < 0.001) but not peripheral neuropathy or myelosuppression.CONCLUSIONIn a real-world setting, patients who received CAPOX had similar OS rates when compared to those receiving FOLFOX in the adjuvant setting in spite of lower RDI. In the high-risk population, CAPOX appears to demonstrate a superior 5-year DFS over FOLFOX.