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Khabre desk
Recent reporting, analysis and explainers from the Oncology desk.
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A pooled analysis of two early-stage trials reported objective responses in 10 of 15 patients with advanced melanoma treated with the investigational TIL therapy amsoki-cel at its recommended dose. The small, non-randomized analysis also found frequent severe blood-related side effects, while a larger trial cohort is ongoing.
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In the phase 2 UNICORN trial, botensilimab plus balstilimab produced major pathological responses in 36% of pMMR and 100% of dMMR colon cancer cohorts before surgery. The small, non-randomized study provides an early clinical signal rather than a treatment comparison.
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In the single-arm MDT-BRIDGE phase 2 study, 142 people with resectable or borderline resectable non-small-cell lung cancer received durvalumab plus chemotherapy before multidisciplinary teams directed them to surgery or chemoradiotherapy. Surgery was performed in 74.6%; survival follow-up is still early.
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In the phase 2 NeoCOAST-2 trial, clearance of circulating tumour DNA during treatment was associated with longer event-free survival in resectable non-small-cell lung cancer. The Dato-DXd combination had the highest reported ctDNA-clearance and 24-month event-free-survival rates among the three arms described.
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A medRxiv preprint reports deep-learning models that predict HPV/p16 status and molecular subtypes of vulvar squamous cell carcinoma from routine tissue slides. The HPV-status model performed better than the model distinguishing all three subtypes.
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In the 31-patient exploratory GDFATHER-NEO trial, nivolumab plus visugromab was associated with higher pathological and radiographic response rates than nivolumab plus placebo before bladder surgery. The small, nonrandomized study was not designed to establish long-term benefit.
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A blinded evaluation of the AI model Ataraxis Breast CTX in SWOG-8814 found its scores were associated with disease-free survival. Results suggesting it could identify chemotherapy benefit were exploratory.
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A medRxiv preprint analysing 520 tumour genomes from eight countries reports similar mutational landscapes in oesophageal and gastroesophageal-junction adenocarcinomas. It also links reflux-associated mutation signatures with obesity in oesophageal adenocarcinoma and reports geographic differences in other signatures.
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An analysis of 783 patients with lymphoma linked a higher proportion of naive-like T cells in CAR T products to longer progression-free survival. The association was also found in an independent validation cohort.
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A Danish nationwide screening effort found conventional HER2-positive status in 62 of 806 people with esophageal squamous cell carcinoma. In a small phase II trial, trastuzumab-based treatment showed responses, while tissue mapping found HER2-poor fibrotic areas enriched for B7-H3.
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An analysis of the MIDAS trial linked molecular features of newly diagnosed multiple myeloma to measurable residual disease after quadruplet induction. A model combining genomic, gene-expression and DNA-methylation data achieved an AUC of 0.77 in a held-out group from the same trial.
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A medRxiv preprint analysing reconstructed data from ten phase 3 kidney-cancer trials finds that the added disease-free-survival benefit of belzutifan may weaken after 12 months. Estimates of the later benefit differ by assessment method.
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In a randomized phase 2 trial of 54 men with high-volume metastatic hormone-naive prostate cancer, talazoparib plus enzalutamide produced a high PSA response rate but no clear advantage over enzalutamide alone. Severe adverse events were more frequent with the combination, and two patients developed fatal acute myeloid leukaemia.
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A Nature Medicine research briefing reports that cachectic weight-loss episodes in 52,236 cancer patients were associated with lower survival and disease progression. The study also identified laboratory and tumour-genotype patterns and trained models to predict impending cachexia risk.
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A medRxiv preprint describes retrospective records for 57 osteosarcoma patients given mifamurtide through access programmes at Memorial Sloan Kettering Cancer Center. Outcomes differed by disease setting, and the authors reported no serious adverse events considered possibly or probably related to the drug.
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A preprint describes a causal digital-twin framework that estimates individual survival benefit from chemoradiotherapy versus radiotherapy alone in head and neck cancer, stratified by HPV status.
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A pooled analysis of 1,038 patients found 86.5% five-year overall survival after neoadjuvant immune checkpoint inhibitors for resectable melanoma. Among patients whose tumours had a major pathological response, estimated five-year survival was 98%.
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A randomized phase 2b trial compared the oncolytic adenovirus VCN-01 plus chemotherapy with chemotherapy alone as first-line treatment for metastatic pancreatic cancer. Progression-free survival was longer in the VCN-01 group, while overall-survival results differed between the trial’s analysis populations.
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In a first-in-human phase 1 trial, the oral WRN inhibitor RO7589831 produced disease control in 74.2% of 66 evaluable patients with MSI cancers, with confirmed partial responses in seven. The study selected two doses for further testing, while tumour biopsies did not provide a conclusive measure of target engagement.
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A medRxiv preprint reports that DIO2 is concentrated in cancer-associated fibroblasts across several solid tumours. In a genetically engineered mouse model, loss of Dio2 in the tumour microenvironment significantly reduced tumour growth.
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In a randomized phase 2 trial, evorpacept plus trastuzumab, ramucirumab and paclitaxel produced higher response rates than the same regimen without evorpacept. The trial met its prespecified response-difference threshold between treatment arms, but not its statistical target against a historical benchmark.
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A South Korean phase 1b/2 trial found a 55% objective response rate when trastuzumab and nivolumab were added to gemcitabine and cisplatin for previously untreated HER2-positive advanced biliary tract cancer. The single-arm results provide early evidence for first-line HER2-targeted chemoimmunotherapy, while randomized confirmation is still needed.
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A Nature Medicine study developed EAGLE, an AI model that identifies esophageal cancer and precancerous lesions on noncontrast chest CT scans. It was validated across 80,612 patients in 12 centres and three countries, including routine and low-dose CT settings.
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A methylation-based blood test detected recurrence of non-viral head and neck cancer with 76.9% sensitivity and 94.6% specificity, and preceded clinical detection by a median of 131 days in 60% of cases where both occurred. Positive results were strongly associated with worse one-year survival.
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NHS England will make trastuzumab deruxtecan, sold as Enhertu, available to around 1,000 women with HER2-low advanced or metastatic breast cancer after their disease progresses following treatment.
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A retrospective study of 2,396 people with advanced NSCLC found clinical-data AI models outperformed single biomarkers and helped physicians predict treatment response and survival.
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In a randomized phase 2 trial, teclistamab produced deeper responses and longer progression-free survival than lenalidomide-dexamethasone in people with high-risk smoldering multiple myeloma. The study found high rates of complete response and minimal residual disease negativity after fixed-duration treatment.