A recent Oncology digest,
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Study Type: Phase III open-label RCT (ENERGIZE/CA017-078), final analysis at 54.5 months median follow-up.

Key Question: Does adding perioperative nivolumab to neoadjuvant gemcitabine-cisplatin (GC) improve outcomes in cisplatin-eligible, previously untreated cT2-T4aN0M0 MIBC?

Key Findings:

• Neither co-primary endpoint was met: pCR 39.1% vs 29.6% (adjusted difference 9.5%, 99.91% CI -2.6 to 21.6); EFS HR 0.94 (95.74% CI 0.71-1.25; P=0.67), with 104 events per arm.
• OS (descriptive only, as EFS testing failed): HR 0.88 (95% CI 0.64-1.21). Grade 3-4 TRAEs were similar (50.0% vs 49.5%), with one treatment-related death in the nivolumab arm.
• Exploratory ctDNA analysis: 55% positive at baseline; baseline and C4D1 positivity were associated with shorter EFS and OS. Clearance by C4D1 was 81.3% (nivolumab plus GC) vs 71.7% (GC).

Clinical Relevance: Neoadjuvant GC followed by cystectomy remains a standard of care, and this trial does not support adding perioperative nivolumab to it, which is relevant to NHS commissioning discussions.

Limitations: ctDNA findings are exploratory and unvalidated for treatment decisions; the abstract does not state whether the trial was blinded.

Study Type: Expert consensus guideline (ESMO Precision Oncology and Taxonomy Committee; iterative review and structured feedback; no original patient data)

Key Question: How should the 2018 ESCAT framework be revised to reflect tumour-agnostic approvals, real-world evidence and resistance biomarkers?

Key Findings:

• Tier I now has three categories (proven, inferred, extrapolated) with identical clinical directive but differing evidence certainty; formal tumour-agnostic gating criteria (ETAC-S) are introduced.
• Tier II is divided into three sub-tiers by evidence type (prospective interventional, high-quality real-world/non-prospective, replicated case-level); Tier X is split into X-A (tested, non-predictive) and X-B (therapy inactive in biomarker-defined population).
• A new four-level resistance scale runs from clinically validated resistance (contraindication) to preclinical/computational evidence (research use only).

Clinical Relevance: Offers a common language for molecular tumour board decisions and genomic report interpretation, which may inform NHS Genomic Medicine Service practice, though local adoption is not addressed in the abstract.

Limitations: Consensus-based, with no validation data or inter-rater reliability testing reported in the abstract.

Study Type: Ad hoc, descriptive updated analysis of a phase III RCT (CAPItello-281), double-blind, placebo-controlled, 1:1 randomisation (n=1012).

Key Question: Does adding capivasertib to abiraterone improve overall survival in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer?

Key Findings:

• At 42% OS maturity (median follow-up 39 months), OS favoured capivasertib: HR 0.82 (95% CI 0.68-0.99; P=0.044); median OS 57.4 vs 46.5 months. The interim HR (26% maturity) was 0.90 (95% CI 0.71-1.15).
• Updated rPFS was consistent with the primary analysis: HR 0.83 (95% CI 0.70-0.99; nominal P=0.033); median 35.5 vs 26.0 months.
• Safety was reported as consistent with the primary analysis; no new signals were described in the abstract.

Clinical Relevance: If confirmed, this supports a biomarker-directed option in PTEN-deficient mHSPC, but UK clinicians would need IHC testing pathways and NICE appraisal before this could influence practice.

Limitations: Analyses were ad hoc and not prespecified, so the OS result is descriptive and its P value, with a CI upper bound close to 1, should be interpreted cautiously.

Study Type: Phase 3 randomised controlled trial (NATALEE), prespecified 6-year follow-up analysis

Key Question: Does adjuvant ribociclib added to NSAI improve overall survival in high-risk HR+/HER2- early breast cancer?

Key Findings:

• OS: HR 0.809 (95% CI 0.661-0.989), absolute 6-year gain 2.1%; nominal 1-sided P = .019, descriptive rather than confirmatory.
• iDFS benefit has widened: HR 0.741 (95% CI 0.646-0.849), absolute 6-year gain 5.3%.
• DDFS (HR 0.744) and DRFS (HR 0.738) support these findings; no new safety signals reported.

Clinical Relevance: First OS signal for adjuvant CDK4/6 inhibition in this setting, relevant to UK discussions on ribociclib's role (including NICE appraisal) for stage II-III HR+/HER2- disease.

Limitations: The OS result is descriptive with a nominal P value, and the modest absolute benefit (2.1%) needs weighing against 3 years of toxicity, which the abstract does not detail.

Study Type: Double-blind, placebo-controlled, phase III RCT (KEYNOTE-866)

Key Question: Does adding perioperative pembrolizumab to neoadjuvant cisplatin/gemcitabine and radical cystectomy improve event-free survival in cisplatin-eligible muscle-invasive bladder cancer?

Key Findings:

• Primary endpoint not met: 60-month EFS 63.5% vs 61.9% (HR 0.88; 95% CI 0.71–1.10; one-sided P = 0.1366) at median follow-up of 60.9 months (n = 907).
• pCR rate was higher with pembrolizumab (44.4% vs 35.8%; difference 8.9%, 95% CI 2.5–15.1), but this did not translate into survival benefit; OS HR 1.00 (95% CI 0.79–1.27).
• Grade ≥3 treatment-emergent adverse events: 80.2% vs 75.1%.

Clinical Relevance: This negative trial tempers enthusiasm for adding perioperative PD-1 blockade to gemcitabine-cisplatin in cisplatin-eligible MIBC, which is relevant to NHS decisions on perioperative immunotherapy and the choice between emerging regimens.

Limitations: The abstract gives no subgroup data (e.g. by PD-L1 status or nodal stage) and EFS was investigator-assessed, so it cannot identify any population that might benefit.

Study Type: Multicentre stepped-wedge cluster-randomised non-inferiority trial (five-year follow-up of SANO).

Key Question: In patients with oesophageal cancer and a clinical complete response after neoadjuvant chemoradiotherapy, does active surveillance achieve long-term survival comparable to standard oesophagectomy?

Key Findings:

• Five-year overall survival: 50% (95% CI 43–57) with surveillance vs 54% (46–64) with surgery; HR 1.17 (0.77–1.77), not statistically significant, consistent across histologic subtypes.
• Five-year cumulative incidence of distant metastases was higher with surveillance: 46% vs 29% (P<.01). Disease-free survival did not differ significantly (HR 1.39, 0.94–2.06).
• 43% (85/198) of surveillance patients avoided oesophagectomy.

Clinical Relevance: Supports surveillance as an option in selected cCR patients, though the excess distant metastases require careful discussion and are relevant to NHS surveillance pathway design and resourcing.

Limitations: Unequal group sizes (198 vs 111) and wide confidence intervals mean modest survival differences cannot be excluded, and the abstract does not report whether formal non-inferiority was met at five years.

Study Type: Randomised phase II proof-of-concept trial (open-label status not stated in abstract), Part 2 of RELATIVITY-104.

Key Question: Does adding relatlimab (anti-LAG-3) to first-line nivolumab plus platinum-doublet chemotherapy improve outcomes in stage IV/recurrent NSCLC?

Key Findings:

• Primary endpoint (BICR-assessed ORR) not met: 51.3% vs 45.0%; PFS HR 0.89 (90% CI 0.72–1.09) in the unselected population.
• In the exploratory PD-L1 ≥1% nonsquamous subgroup: ORR 58.0% vs 39.6%; PFS HR 0.68 (90% CI 0.46–1.01); OS HR 0.60 (90% CI 0.38–0.94).
• Safety was described as manageable and consistent with prior reports; no specific toxicity data in abstract.

Clinical Relevance: No practice change; the combination remains investigational in NSCLC, with the phase III RELATIVITY-1093 trial testing the PD-L1 ≥1% nonsquamous signal.

Limitations: The subgroup findings are exploratory, post hoc in nature, and from a small phase II trial, so they are hypothesis-generating only and at high risk of chance findings.

Study Type: Randomised, double-blind, placebo-controlled phase 3 trial (final analysis; n=342).

Key Question: Does adding pembrolizumab to chemotherapy improve outcomes in PD-L1-positive (CPS ≥1) HR+/HER2- advanced breast cancer after progression on endocrine-based therapy?

Key Findings:

• PFS (primary endpoint, interim analysis): HR 0.74 (95% CI 0.58–0.95); median 6.7 vs 6.0 months, a statistically significant but small absolute gain. In CPS ≥10, HR 0.59 (0.35–0.98), numerical only.
• OS (final analysis): no benefit, HR 1.04 (0.81–1.33); median 21.0 vs 22.2 months.
• Grade ≥3 treatment-related AEs 38% vs 33%; discontinuation for treatment-related AEs 11% vs 5%.

Clinical Relevance: The PFS gain was not accompanied by any OS benefit, so this does not support routine use of pembrolizumab in HR+/HER2- disease, though it informs ongoing discussions around immunotherapy in this subtype.

Limitations: The sample size was reduced after amendment because of low PD-L1 prevalence, limiting power, particularly for subgroup and OS analyses.