BREAST: the utility of surrogate endpoints is often uncertain, particularly in the neoadjuvant setting; an analysis of 11 RCTs identified invasive disease-free survival as a reliable surrogate endpoint, so long as follow-up was sufficiently long.

IMMUNOTHERAPY: autologous T cells engineered to express a NY-ESO-1/LAGE-1a T cell receptor were well tolerated but delivered only modest efficacy in a phase 1 study of NSCLC (ORR 6%).

OVARIAN: in a randomised phase 3 study for patients with advanced disease, treatment with the PARP inhibitor rucaparib was associated with inferior survival compared with chemotherapy (median OS 19 versus 25 months, respectively).

EPIDEMIOLOGY: an international analysis of the impact of the COVID pandemic on cancer reveals reductions in screening (39%), diagnoses (23%) and treatment (28%); middle income countries fared worse than high income countries.

DRUG TARGETS: the ERBB2-ERBB3 bispecific antibody zenocutuzumab delivered ORR 30% and median DoR 11 months in a basket study enrolling patients whose tumours harbour a rare NRG1 fusion; the largest tumour groups were NSCLC and pancreatic.

ENDOMETRIAL: data from the US (ACS) highlight endometrial as the only cancer where survival has decreased over the last 4 decades; this is further exacerbated by marked racial disparity (worse outcomes for Black women) and under funding of research.

CLINICAL TRIALS: analysis of three phase 3 trials in advanced bladder cancer highlight differential censoring as potentially resulting in false positive outcomes; drop out of high performance patients from the control arm may have contributed.

IMMUNOTHERAPY: a personalised neoantigen-specific anti-cancer vaccine (autogene cevumeran) produced specific T cell responses in patients with advanced disease but has not, as yet, shown convincing efficacy.

IMMUNOTHERAPY: the addition of IL-15 armour to a glypican-3 (GPC3) targeted CAR T increased ORR in solid tumours from 0% to 33% mediated by increased CAR T expansion, at the expense of increased (but controllable) cytokine release syndrome.

BREAST: in a first in human study, an ERBB2 + 4-1BB bispecific fusion protein (cinrebafusp alfa) delivered ORR 25% at the active dose for patients with advanced ERBB2+ (HER2+) disease; infusion reactions were the main AE but were manageable.

PANCREAS: in preclinical kras mutant models, the wild-type allele exerts suppressive effects, with loss of wild-type Kras (known to occur in primary human cancers) accelerating disease initiation and rendering tumours more sensitive to MEK inhibition.

HAEM: preclinical studies suggest that EZH2 inhibition enhances the activity of CAR T cells; this approach has been taken into the clinic in the US (NCT05934838 and NCT05994235).

PROSTATE: in patients with a BRCA1/2 or PALB2 mutation receiving PARP inhibition for advanced disease, progression was associated with reversion mutation in 79% of cases; in those with homozygous deletions, selection for wild-type clones was observed.

DRUG TARGETS: a first in human basket study of a PRMT5 inhibitor (AMG 193) for patients with MTAP deleted tumours delivered ORR 21% for those receiving active and tolerated doses; toxicity was generally manageable (GI, fatigue, hypersensitivity).

HAEM: the CD30 ADC brentuximab vedotin improved outcomes for patients with relapsed refractory DLBCL regardless of CD30 expression; activity in CD30-negative lymphomas implies an indirect MoA (possibly immune mediated) or payload dissociation.

PROSTATE: combined PDL1 and CTLA4 inhibition delivered ORR 19% in a small phase 2 study of mCRPC; known IO biomarkers showed limited utility highlighting the need for better patient selection.

CLINICAL TRIALS: pts with Duffy blood group undergoing cancer therapy were more likely to develop neutropaenia but not more likely to experience febrile neutropaenia, providing further evidence that normal neutrophil ranges are misleading for these pts

DRUG TARGETS: advances in chemistry & structural biology continue to make mutant-specific inhibitors a reality; a novel approach to mutant-selective inhibition of AKT1 E17K avoids the hyperglycaemia induced by inhibition of wild-type AKT1.

This scathing assessment places the Cass report where it belongs, as part of an unfortunate history of medicine being subverted as a tool to enforce conservative social norms.

HAEM: CAR-T cell therapy has shown only modest efficacy in acute myeloid leukaemia (AML); clinical studies now identify a novel resistance mechanism whereby therapy induced cytokine release supports AML cell survival resulting in T cell exhaustion.