The Christie School of Oncology: Christie Research Publications Repository
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Camizestrant in Combination with Three Globally Approved CDK4/6 Inhibitors in Women with ER+, HER2- Advanced Breast Cancer: Results from SERENA-1
No full textPURPOSE: This trial investigated the safety and tolerability of camizestrant with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in women with estrogen receptor-positive, HER2- advanced breast cancer. PATIENTS AND METHODS: SERENA-1 (NCT03616587) is a phase I, multipart, open-label study in women with refractory estrogen receptor-positive, HER2- advanced breast cancer. Patients received oral once-daily camizestrant 75 or 150 mg plus abemaciclib; camizestrant 75, 150, or 300 mg plus palbociclib; or camizestrant 75 mg plus ribociclib 400 or 600 mg. Safety/tolerability, pharmacokinetics, efficacy, and impact on estrogen receptor 1 mutation ctDNA were assessed. RESULTS: By September 16, 2024 (data cutoff), 53 patients had received camizestrant plus abemaciclib, 78 camizestrant plus palbociclib, and 60 camizestrant plus ribociclib. Patients had a median of 2 (range, 0-7) prior regimens for advanced disease; 83% had received a prior CDK4/6i and 59% prior fulvestrant. The most common treatment-emergent adverse events for camizestrant 75 mg (phase III dose) plus each CDK4/6i were diarrhea [with abemaciclib (87.5%)] and neutropenia [with palbociclib (80%) and ribociclib (32.1% for 400 mg and 53.1% for 600 mg)]. The median camizestrant tmax was ∼4 hours postdose across combinations, with an estimated half-life of 9.5 to 17 hours. No clinically meaningful drug-drug interactions were evident. In this heavily pretreated population, CBR24 was 49.5% and the median progression-free survival was 7.4 months (95% confidence interval, 5.3-9.3), with antitumor activity across all combinations, including patients previously treated with CDK4/6i and/or fulvestrant, with or without estrogen receptor 1 mutation. CONCLUSIONS: Camizestrant is well tolerated, with antitumor activity in combination with CDK4/6i. These results support the evaluation of camizestrant 75 mg plus standard CDK4/6i doses in phase III trials
Viewpoint: optimising cancer treatment to reduce its environmental impact
No full textIt is widely accepted that treatment and care for patients with cancer must and should happen, as it is what everyone would want for themselves and their loved ones. Everyone wants the best possible care, but climate change and the extreme weather that it causes are increasingly affecting everyone including patients in negative ways. To continue giving the best possible cancer care without harming our environment and therefore patients, there is a need to optimise care. Through improving efficiency, reducing travel, using renewable energy and other measures it is possible to limit our environmental impact whilst still giving the best care available. In many cases this creates a win-win-win scenario for patients and the environment and, in many cases, significant cost savings
Co-designing 'gene', a smartphone app for genetics education and empowerment with and for the British Pakistani community: a methodological summary of the GENE-Ed project
No full textINTRODUCTION: A lack of culturally appropriate genetic information prevents the British Pakistani community from engaging with genetic services. The GENE-Ed project focussed on the development of an educational app with and for the Pakistani community. A secondary aim was understanding how to engage the community in research. METHODS: We used an iterative co-design and co-creation approach including four phases to develop the Gene app. Phase 1 included seven interviews with community members to explore genetics understanding and define the requirements. Phase 2 included reviewing smartphone apps and research on digital patient-facing interventions for genetics understanding. Phase 3 included developing the app and obtaining initial feedback. In Phase 4, feedback was obtained from five community members using the System Usability Scale (SUS), a bespoke survey and observations. RESULTS: Four themes were identified in the interviews: current awareness of genetics; consanguinity, religion and cultural influence; presenting genetics information in a new digital resource and dissemination; information-sharing and uptake. The reviews highlighted an absence of culturally sensitive, accessible and evidence-based digital resources. Initial feedback included altering the animations and images within the app and simplifying the text. The mean SUS score was 87, indicating excellent usability. The written information, animations and videos were acceptable to participants, and they tended to trust the information in the app. During feedback, community members responded well to different methods but struggled with written open-ended survey questions. CONCLUSION: The co-design approach was essential to developing an acceptable resource for the British Pakistani community. Future clinical testing is needed
The promise of radiotherapy in high-risk non-muscle invasive bladder cancer
No full textGlobal shortages, toxicities, and high levels of incomplete treatment with Bacillus Calmette Guerin (BCG) for non-muscle invasive bladder cancer has resulted in increasing interest in alternative treatments. Radiotherapy is not the standard of care for non-muscle invasive bladder cancer (NMIBC), despite being routinely used in muscle invasive bladder cancer. Modern techniques and advances in technology mean that radiotherapy can be delivered with increased precision in reducing normal tissue damage. Developing novel biomarker approaches, together with combination approaches with radiosensitisers and other systemic treatments, means that radiotherapy could offer greater benefits than current treatments with BCG or surgery. This review summarises the current landscape and future potential of radiotherapy for high-risk NMIBC
Mammographic density assessed using deep learning in women at high risk of developing breast cancer: the effect of weight change on density
No full textPurpose:High mammographic density (MD) and excess weight are both associated with increased risk of breast cancer. Classically defined percentage density measures tend to increase with reduced weight due to disproportionate loss of breast fat, however the effect of weight loss on artificial intelligence-based density scores is unknown. We investigated an artificial intelligence-based density method, reporting density changes in 46 women enrolled in a weight-loss study in a family history breast cancer clinic, using a volumetric density method as a comparison.Methods:We analysed data from women who had weight recorded and mammograms taken at the start and end of the 12-month weight intervention study. MD was assessed at both time points using a deep learning model trained on expert estimates of percent density called pVAS, and the volumetric density software Volpara(TM).Results:Mean (standard deviation) weight of participants at the start and end of the study was 86.0 (12.2) and 82.5 (13.8) respectively; mean (standard deviation) pVAS scores were 35.8 (13.0) and 36.3 (12.4), and Volpara volumetric percent density scores were 7.05 (4.4) and 7.6 (4.4).The Spearman rank correlation between reduction in weight and change in density was 0.17 (-0.13 to 0.43, p = 0.27) for pVAS and 0.59 (0.36 to 0.75, p<0.001) for Volpara volumetric percent density.Conclusion:pVAS percentage density measurements were not significantly affected by change in weight. Percent density measured with Volpara increased as weight decreased, driven by changes in fat volume
Impact of platinum-based chemotherapy and CTLA-4 inhibition on acquired resistance to first-line anti-PD-1/PD-L1 agents in non-small cell lung cancer: a systematic review and reconstructed individual patient data analysis
No full textBACKGROUND: Acquired resistance is defined as disease progression following an initial response to immune checkpoint inhibitors (ICI). The impact of adding platinum-based chemotherapy (PCT) or anti-CTLA-4 agents to PD-(L)-1 inhibitors on acquired resistance is currently unknown. METHODS: Systematic research by January 31, 2025 identified randomized clinical trials (RCTs) evaluating first-line ICI as monotherapy (mono-ICI) or in combination with PCT (mono-ICI + PCT), CTLA-4 inhibitors (combo-ICI), or both (combo-ICI + PCT) in metastatic non-small-cell lung cancer (NSCLC). RCTs reporting duration of response (DoR) data were eligible. Acquired resistance rates at 6 and 12 months were estimated from DoR curves. Aggregate data based on type of regimens were reported with risk ratio (RR) and pooled by random effect model. Primary and secondary endpoints were respectively the indirect comparison of acquired resistance risk between PCT-containing versus PCT-free regimens and between anti-CTLA-4 containing versus anti-CTLA-4 free regimens, respectively. Time-to-event outcomes were retrieved from Kaplan-Meier (KM) curves using individual patient data (IPD) and compared by log rank tests. This study was registered to the PROSPERO online platform (CRD42025639320). FINDINGS: Nineteen RCTs were included. 6- and 12-months acquired resistance rates were 16.5%-34.1% (mono-ICI), 26.4%-47.8% (mono-ICI + PCT), 19.0%-33.0% (combo-ICI), and 28.4%-47.1% (combo-ICI + PCT). A higher risk of acquired resistance was suggested from indirect comparisons of mono-ICI + PCT versus mono-ICI (12-months RR: 1.46, 95% CI 1.23-1.75) and of combo-ICI + PCT versus combo-ICI (12 months RR: 1.36, 95% CI 1.06-1.73). Using the reconstructed patient-level data, median DoR was 5-7 months significantly shorter with PCT-containing compared to PCT-free regimens. The addition of anti-CTLA-4 agents did not impact on acquired resistance. INTERPRETATION: Although insufficient RCTs reported acquired resistance rates stratified by specific factors influencing DoR (i.e., PD-L1, TMB) for such analyses to be included in this report, the increased acquired resistance risk observed with PCT-containing regimens highlights the potential value of tailoring first-line treatment strategies in NSCLC on the basis of individual risk of resistance to ICI. FUNDING: This research did not receive any specific grant from funding agencies
New systemic treatment paradigms in advanced biliary tract cancer and variations in patient access across Europe
No full textIn recent years, treatment options for patients with advanced biliary tract cancer (BTC) have increased significantly due to the positive results from phase 2/3 clinical trials of immune checkpoint inhibitors, combined with chemotherapy, and molecularly targeted agents. These advances have led to the need for molecular testing to identify actionable alterations and patients amenable to targeted therapies. However, these improvements have brought with them many questions and challenges, including the identification of resistance mechanisms and therapeutic sequences. In this Series paper we aim to provide an overview of the current systemic treatment options for patients with BTC, highlighting disparities in access to innovative treatments and molecular testing across European countries, which lead to inequalities in the possibilities of treating patients with advanced BTC. We also discuss how ongoing European collaborative projects, such as the COST Action Precision-BTC-Network CA22125, supported by COST (European Cooperation in Science and Technology), linked to the European Network for the Study of Cholangiocarcinoma (ENSCCA), can help overcome these disparities and improve the current scenario
Management of advanced germ cell tumours
No full textBACKGROUND: Male germ cell tumours are an exemplar of a highly curably malignancy and represent the most frequent solid malignancy among men under the age of 40. The majority of cases are detected while the tumour is confined to the testicle where cure rates exceed 99%. Even in cases of metastatic disease expansion, cure rates remain extraordinary compared to other malignancies, owing to the unique sensitivity of most germ cell tumour components to cisplatin-based chemotherapy. SUMMARY: The treatment of metastatic germ cell tumours is adapted to (i) primary histology (seminoma versus non-seminoma or mixed germ cell tumour), (ii) disease spread (clinical stage IIA/B versus IIC/III), and (iii) clinical risk according to the International Germ Cell Cancer Collaborative Group classification. Across all metastatic stages, the combination of bleomycin, etoposide, and cisplatin is most commonly used. In non-seminomas, post-chemotherapy residual mass resection is the second cornerstone of treatment. Among patients who relapse after first-line chemotherapy, platinum-based conventional dose or high-dose chemotherapy regimens can still achieve cure in 50% of patients. Outcomes for patients with multiple relapses, however, remain dissatisfactory and novel treatment approaches are urgently needed. High cure rates demand cautious consideration of possible long-term side effects. Novel strategies are being explored to mitigate the risk of long-term morbidity without lowering the outstanding cure rates. KEY MESSAGES: (i) Advanced germ cell tumours are highly curable with cisplatin-based combination chemotherapy and often surgical post-chemotherapy residual mass resection. (ii) Novel de-escalation strategies and survivorship programs aim to mitigate the risk of long-term treatment side effects. A lack of effective molecularly targeted treatment approaches pinpoints the need for novel treatments for multiply relapsed, platinum-resistant disease
Digital pathology biomarkers for guiding radiotherapy-based treatment concepts in prostate cancer - a systematic review and expert consensus
No full textCurrent risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity, and digital pathology (DP) combined with artificial intelligence (AI) tools (DP-AI) may offer a solution to this challenge. The aim of this work is to summarize the role of DP-AI for PCa patients treated with radiotherapy (RT), and to point out future areas of research. We conducted (1) a systematic review on the evidence of DP-AI for patients treated with RT and (2) a survey of experts using a modified Delphi method, addressing the current role of DP-AI in clinical and research practice to identify relevant fields of future development. Eleven studies investigated DP-AI in PCa RT, with most using the multimodal AI (MMAI) classifier and four ongoing studies are currently prospectively testing the DP-AI performance. DP-AI showed strong prognostic and predictive performance for endpoints like distant metastasis free survival and overall survival, outperforming traditional risk models and assisting treatment decisions such as androgen deprivation therapy (ADT) duration. Fifty-one and 35 experts responded to round 1 and round 2 of the survey respectively. Questions with ≥75 % agreement were considered relevant and included in the qualitative analysis. Survey results confirmed growing adoption of DP scanners, although regional differences in re-imbursement mechanisms and availability persist, with experts endorsing DP-AI's potential across localized, postoperative, and metastatic settings, though further prospective validation is needed. DP-AI tools show strong prognostic and predictive potential in various PCa by guiding patient stratification and optimising ADT duration in primary RT. Prospective studies and validation in cohorts using modern diagnostic and treatment methods are needed before broad clinical adoption