Publications by authors named "Martin Stockler"
Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54).
View Article and Find Full Text PDFBackground: Despite advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC), primary and secondary resistance to current therapies remains. Elevated circulating sphingolipids are associated with poor outcomes in patients with mCRPC, including therapeutic resistance and shorter overall survival. PCPro is a clinically accessible, regulatory compliant plasma lipid biomarker of poor prognosis in mCRPC, which incorporates prognostic sphingolipids.
View Article and Find Full Text PDFClinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period.
View Article and Find Full Text PDFImportance: Observed treatment effects on overall survival (OS) differed substantially in the first 2 randomized clinical trials of lutetium Lu 177 vipivotide tetraxetan (Lu-177) prostate-specific membrane antigen (PSMA) in metastatic castration-resistant prostate cancer.
Objective: To investigate factors associated with the observed difference in treatment effects on OS, including differences in the risk of crossover from randomized treatment after disease progression.
Design, Setting, And Participants: This comparative effectiveness study used individual participant data from 2 randomized clinical trials, TheraP (A Randomised Phase 2 Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer [ANZUP Protocol 1603]) (n = 200), recruited from February 2018 to September 2019 in Australia, and published data from VISION (An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer) (n = 831), recruited from June 2018 to October 2019 in North America and Europe.
Article Synopsis
- * The study investigates how the HSD3B1 gene, which can enhance androgen synthesis, affects outcomes in mHSPC patients receiving ADT, specifically focusing on those with low-volume disease participating in the ENZAMET trial.
- * Findings show that patients with the adrenal-permissive HSD3B1 allele had better progression-free survival and overall survival when treated with combined ADT and androgen receptor antagonists, suggesting that genetic factors can influence treatment effectiveness and outcomes in prostate cancer. *
Background: Primary hypogonadism is a recognised complication in survivors of testicular cancer. However, secondary hypogonadism can result from other causes that suppress the hypothalamic-pituitary axis, including obesity, high dose glucocorticoids, chronic end organ failure, and diabetes. The aim of this study was to explore low total serum testosterone in Australian survivors of testicular cancer and examine associations with body mass index, age, and prior chemotherapy use.
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- This clinical trial tested the effectiveness of an oral cannabis extract (THC:CBD) on adults experiencing severe nausea and vomiting from chemotherapy, despite using standard anti-nausea medications.
- The results showed that the cannabis extract significantly increased the rate of complete responses (no vomiting or need for rescue meds) from 8% to 24% compared to a placebo.
- While participants reported some mild side effects like sedation and dizziness, there were no serious adverse events linked to the cannabis treatment.
Article Synopsis
- - This research examines why positive treatment effects seen in the first interim analysis of clinical trials may decline in later analyses, focusing on issues like overestimation bias, non-proportional hazards, and varied recruitment.
- - The study analyzed 71 oncology randomized clinical trials, showing that hazard ratios often overestimate treatment effects, especially when fewer events have occurred by the interim analysis.
- - The findings highlight the need to apply adjusted hazard ratios to reduce overestimation bias and stress the importance of considering various factors when reporting on positive interim analysis results.
Article Synopsis
- The study examined whether comprehensive geriatric assessment (CGA)-guided care enhances health-related quality of life (HRQL) in older cancer patients compared to standard care.
- Meta-analyses showed a potential moderate improvement in HRQL scores at 3 months, though results were not definitive and depended on the size and type of trials.
- Overall, findings suggested that larger RCTs and those requiring CGA before cancer treatment were more likely to show better HRQL outcomes.
Background: We aimed to summarize survival data from RCTs in patients with GO adenocarcinoma; estimate and explain worst-, typical-, and best-case-scenarios of survival time; and determine if simple multiples of median overall survival (mOS) could estimate these percentiles.
Methods: We systematically searched RCTs of systemic therapies for GO adenocarcinoma published 2000-2022. The following key percentiles were extracted from overall survival curves: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case).
Background: Enzalutamide and lutetium-177 [Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer.
View Article and Find Full Text PDFBackground: Prognostic models have been developed using data from a multicentre noncomparative study to forecast the likelihood of a 50% reduction in prostate-specific antigen (PSA50), longer prostate-specific antigen (PSA) progression-free survival (PFS), and longer overall survival (OS) in patients with metastatic castration-resistant prostate cancer receiving [Lu]Lu-PSMA radioligand therapy. The predictive utility of the models to identify patients likely to benefit most from [Lu]Lu-PSMA compared with standard chemotherapy has not been established.
Objective: To determine the predictive value of the models using data from the randomised, open-label, phase 2, TheraP trial (primary objective) and to evaluate the clinical net benefit of the PSA50 model (secondary objective).
Background: Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC.
Methods: IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120).
Article Synopsis
- - This phase II study tests whether alternating the cancer drugs osimertinib and gefitinib can slow down resistance development in advanced non-small cell lung cancer with the EGFR T790M mutation in 47 patients.
- - The primary goal was to measure progression-free survival (PFS) at 12 months, but the results showed a PFS rate of only 38%, which didn't meet expectations.
- - Despite some improvement in specific genetic markers associated with treatment resistance, the study indicates that managing resistance in cancer treatments is complex and involves more factors than just targeting known mutations.
Article Synopsis
- The study aims to assess the baseline symptom burden experienced by patients with recurrent ovarian cancer and its relationship with progression-free survival and overall survival.
- Analysis involved 948 patients with either platinum-resistant or potentially platinum-sensitive recurrent ovarian cancer receiving advanced chemotherapy, revealing that a significant majority experienced mild to severe symptoms, including pain, fatigue, and anxiety.
- Results showed that higher symptom burden was linked to reduced progression-free survival and overall survival, highlighting the need for effective symptom management in clinical settings and trials.
Purpose: Many people with cancer (patients) want to know their prognosis (a quantitative estimate of their life expectancy) but this is often not discussed or poorly communicated. The optimal timing of prognostic discussions with people with advanced cancer is highly personalised and complex. We aimed to find, organise, and summarise research regarding the timing of discussions of prognosis with people with advanced cancer.
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- Some cancer patients think their treatments will cure them or give them more time to live, but many are not really clear about their actual chances.
- Researchers talked to 104 patients and their doctors to see how they view the benefits of their cancer treatments.
- They found that a lot of patients expect their treatments to help them more than their doctors believe it will, especially when it comes to quality of life versus length of life.
Background: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [Ga]Ga-PSMA-11 and 2-[F]fluoro-2-deoxy-D-glucose (2-[F]FDG) PET-CT.
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- The study aimed to assess whether oncologists tend to overestimate expected survival time (EST) for patients with advanced cancer by comparing it to actual observed survival time (OST).
- It found that oncologists’ estimates of EST were generally accurate, with about 50% of the EST being longer than OST, though 28% of estimates were imprecise within a specific range.
- The results indicate that oncologists are equally likely to overestimate or underestimate survival, and using simple multiples of EST can effectively outline worst-case, typical, and best-case survival scenarios.
To summarise the prognostic value of patient-reported outcomes (PROs) in advanced gastro-oesophageal (GO) cancer. We systematically searched multiple databases using search terms related to advanced GO cancer, PRO and prognosis. Studies examining the relationship between baseline PROs and prognosis were included.
View Article and Find Full Text PDFBackground: Sentinel node-based management (SNBM) is the international standard of care for early breast cancer that is clinically node-negative based on randomised trials comparing it with axillary lymph node dissection (ALND) and reporting similar rates of axillary recurrence (AR) without distant disease. We report all ARs, overall survival, and breast cancer-specific survival at 10-years in SNAC1.
Methods: 1.