A recent Oncology digest,
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Study Type: Prospective multicentre cohort study (real-world evidence)

Key Question: Does comprehensive genomic profiling (CGP) offer added clinical value over standard reimbursed local NGS panels in guiding targeted therapy decisions for advanced cancer patients?

Key Findings:

• CGP (FoundationOne CDx) was successful in 93% of 1000 patients; among those with paired testing, 48% gained ≥1 additional molecular tumour board (nMTB) recommendation versus local NGS alone.
• CGP more than doubled targeted therapy recommendations, with nMTB issuing recommendations for 61% of patients overall.
• Only 23% of evaluable patients (n=586) received the recommended therapy; non-adherence was mainly due to drug unavailability (25%), clinical deterioration (24%), and patient choice (17%); of those treated, 48% enrolled in clinical trials.

Clinical Relevance: These findings support broader adoption of CGP within NHS molecular diagnostic pathways to increase actionable findings and trial access, but highlight persistent access barriers to matched therapies even when detected.

Limitations: Real-world implementation gaps (drug access, rapid deterioration) substantially limited translation of genomic findings into actual treatment, and the study lacks survival/outcome data to confirm clinical benefit.

Study Type: Phase 2, open-label, sequential-cohort, dose-selection study

Key Question: Is anselamimab (an amyloid fibril–targeting monoclonal antibody) safe and tolerable when combined with standard anti-plasma cell dyscrasia therapy in AL amyloidosis?

Key Findings:

• All 25 participants experienced ≥1 TEAE (mostly mild-moderate); 64% had serious TEAEs, 16% discontinued due to TEAEs, and 12% had fatal TEAEs—none adjudicated as drug-related; no dose-limiting toxicities.
• Best cardiac response occurred at Week 50 (47.4% of evaluable patients); best renal response at Weeks 62/98 (85.7% of evaluable patients).
• Tolerability was similar whether combined with CyBorD alone or CyBorD plus daratumumab.

Clinical Relevance: AL amyloidosis remains under-recognised and hard to treat in UK practice; anselamimab represents a novel amyloid-clearing approach that could complement existing NHS-available regimens (e.g., daratumumab-CyBorD) if efficacy is confirmed in larger trials.

Limitations: Small, non-randomised, open-label cohort without a comparator arm limits conclusions on efficacy and causal attribution of adverse events.

Study Type: Multicentre retrospective cohort study (international, real-world, five cohorts)

Key Question: Does direct tumour-adipocyte contact (TAC/SARIFA), assessed on routine H&E slides, predict survival in resected pancreatic ductal adenocarcinoma (PDAC)?

Key Findings:

• TAC/SARIFA positivity (53% of cases, good interobserver agreement, κ=0.71) was independently associated with worse OS (pooled median 14.1 vs 28.0 months; HR 1.84, 95% CI 1.59–2.14, p<0.001).
• Prognostic effect was stronger in men (HR 2.46) than women (HR 1.50), with significant sex interaction (p<0.001).
• Adjuvant chemotherapy benefit was greater in TAC/SARIFA-positive patients; positive tumours showed upregulated LEP and KRT14, suggesting a biologically aggressive, basal-like phenotype.

Clinical Relevance: This simple, low-cost H&E-based biomarker could improve risk stratification and inform adjuvant treatment decisions in resected PDAC within NHS pathology workflows without additional molecular testing.

Limitations: Retrospective design across heterogeneous cohorts limits causal inference and standardisation of chemotherapy regimens/follow-up.

Study Type: Phase II RCT (extended follow-up and biomarker subgroup analysis of Arm C, AIO-STO-0417/moonlight trial)

Key Question: Which biomarkers identify patients with metastatic gastroesophageal adenocarcinoma most likely to benefit from FLOT plus nivolumab, given the toxicity burden of triplet immunochemotherapy?

Key Findings:

• FLOT + nivolumab (n=52): mPFS 7.0 months, mOS 14.6 months; CPS≥1 showed non-significant trend toward longer survival (mOS 17.4 vs 10.0 months, p=0.15).
• Low neutrophil-to-lymphocyte ratio (NLR) and low monocyte-to-lymphocyte ratio (MLR) trended toward improved survival (mOS 25.5 vs 6.8 months and 28.4 vs 8.3 months respectively).
• Combined CPS≥1 and low MLR identified a subgroup with significantly enhanced survival (mOS 32.3 vs 7.4 months, p=0.044); quality-of-life data showed reduced pain but worse physical functioning and fatigue.

Clinical Relevance: These exploratory biomarkers (PD-L1 CPS combined with MLR) could help UK oncologists select patients for intensified FLOT-immunotherapy regimens where treatment intensity and toxicity must be balanced against expected benefit, informing future NHS trial design or MDT decision-making.

Limitations: Small subgroup sizes and non-significant p-values for most comparisons limit definitive conclusions; findings are hypothesis-generating pending prospective validation.

Study Type: Literature review (narrative)

Key Question: Does prophylactic G-CSF use reduce the risk of severe neutropenia and febrile neutropenia (FN) in patients treated with antibody-drug conjugates (ADCs)?

Key Findings:

• Available evidence supports prophylactic G-CSF (filgrastim, lenograstim, pegfilgrastim) as effective in reducing FN and severe neutropenia associated with ADC therapy.
• Data specifically evaluating G-CSF as secondary prophylaxis (after a neutropenic event) remain limited.
• No pooled incidence rates, effect sizes, or comparative statistics are reported in the abstract.

Clinical Relevance: With increasing NHS use of ADCs (e.g., trastuzumab deruxtecan, sacituzumab govitecan) across breast, urothelial, and other cancers, clinicians should consider guideline-concordant G-CSF prophylaxis to reduce FN-related hospitalisation and treatment delays.

Limitations: As a narrative review without systematic methodology, it cannot provide quantitative pooled estimates, and evidence for secondary prophylaxis specifically is sparse.

Study Type: Phase 1 dose-finding trial (3+3 design)

Key Question: Is ODM-209, an oral CYP11A1 inhibitor blocking all steroidogenesis, safe and clinically active in heavily pretreated mCRPC and advanced breast cancer?

Key Findings:

• All 38 participants (34 mCRPC, 4 aBC) experienced AEs; most common were fatigue (53%) and peripheral oedema (34%); 24% had grade ≥3 treatment-related AEs, including adrenal insufficiency in 8%.
• PSA50 response in 29% of mCRPC patients overall, rising to 47% (9/19) in those with activating AR-LBD mutations, with 5.6-month median treatment duration in this subgroup.
• Partial clinical response in 19% (3/16) evaluable mCRPC patients; no responses observed in aBC.

Clinical Relevance: ODM-209 offers a novel mechanism with signal of activity in mCRPC patients harbouring AR-LBD mutations—a resistant subgroup with limited options post-AR inhibitor and taxane therapy relevant to UK treatment pathways.

Limitations: Small, heterogeneous sample with no control arm limits conclusions on efficacy and requires confirmation in larger randomised trials.

Study Type: Retrospective analysis using target trial emulation (causal inference methodology applied to RCT data)

Key Question: Does protocol-guided dose reduction or treatment delay during VDC/IE induction chemotherapy for Ewing Sarcoma compromise event-free survival (EFS)?

Key Findings:

• Dose reduction showed a non-significant protective trend for EFS (HR 0.69, 95% CI 0.39–1.24).
• Time delay showed a non-significant detrimental trend (HR 1.02, 95% CI 0.90–1.15), with mild worsening as delay increased.
• Neither adjustment reached statistical significance for harming EFS.

Clinical Relevance: Supports current NHS practice of using protocol-directed dose modifications to manage toxicity in Ewing Sarcoma without apparent compromise to survival outcomes, reassuring clinicians managing treatment-related toxicity in paediatric/AYA sarcoma units.

Limitations: Wide confidence intervals and non-significant estimates limit definitive conclusions, and residual confounding may persist despite propensity score adjustment in this observational emulation.

Study Type: Prospective cohort study (diagnostic performance analysis, PROMPT study)

Key Question: Does a tumour-first workflow (TFW) outperform family history (FH)-based referral for identifying germline pathogenic variants (gPVs) in metastatic prostate cancer patients when universal germline testing is not feasible?

Key Findings:

• Germline testing detected gPVs in 36/452 patients (7.8%); TFW referral criteria captured 22/36 carriers (61%), including 100% of high-risk gene carriers (BRCA2, BRCA1, PALB2).
• TFW identified significantly more carriers than modelled FH-based referral (22 vs 8; p<0.001), with higher PPV (51% vs 13%) and lower number needed to test (2.0 vs 7.9).
• Diagnostic cost per detected gPV was substantially lower with TFW (€998 vs €12,246).

Clinical Relevance: As UK guidance moves toward universal germline/tumour testing in mPCa but resource constraints persist across NHS genomic pathways, TFW offers a pragmatic, cost-effective triage strategy ensuring high-risk actionable variants (relevant to PARP inhibitor eligibility and cascade testing) are not missed.

Limitations: TFW missed 39% of gPV carriers overall (mainly lower-penetrance genes ATM/CHEK2), and FH-based comparison was modelled rather than prospectively applied.