The edition · Oncology
After resistance: new moves in blood, lung, bowel and breast cancer
Azacitidine–venetoclax challenges induction chemotherapy in fit AML; consolidation immunotherapy shows promise in limited-stage SCLC; cetuximab adds nothing to bevacizumab with FOLFOXIRI in colorectal cancer; and an all-oral regimen extends control after CDK4/6 inhibition in breast cancer.
The edition in brief
In the phase 2 PARADIGM trial, 172 adults with AML who were fit for induction chemotherapy were randomised to azacitidine–venetoclax or standard induction; event-free survival was longer with the chemotherapy-free regimen (median 14.5 vs 6.2 months, hazard ratio 0.57), with fewer severe infections and bleeds. Favourable-risk subtypes were excluded and the endpoint was event-free, not overall, survival, so this challenges rather than overturns induction in fit patients. A small phase 2 trial (GASTO-1052A, 98 patients, stopped early) found consolidation toripalimab after chemoradiotherapy for limited-stage small-cell lung cancer improved progression-free (hazard ratio 0.55) and overall survival (0.39) with mild toxicity — promising but needing a larger trial. A meta-analysis of 561 patients with metastatic colorectal cancer found FOLFOXIRI plus cetuximab gave no better survival or response than FOLFOXIRI plus bevacizumab, while causing more hypomagnesaemia and acneiform rash — a reason to favour the bevacizumab combination on tolerability. A clinic pearl: as checkpoint inhibitors move into earlier and consolidation settings, screen for immune-related adverse events at every visit and, for anything beyond mild, hold the drug and start corticosteroids early. Finally, the phase 3 evERA trial in 373 patients with ER-positive, HER2-negative advanced breast cancer progressing after a CDK4/6 inhibitor found an all-oral giredestrant–everolimus regimen extended progression-free survival versus standard endocrine therapy plus everolimus (8.8 vs 5.5 months overall; 10.0 vs 5.5 months, hazard ratio 0.38, in ESR1-mutated tumours), with similar toxicity — the benefit concentrated in ESR1-mutated disease.
Azacitidine–venetoclax challenges induction chemotherapy in fit AML
In fit AML, azacitidine–venetoclax outperformed induction on event-free survival with less toxicity — a result to weigh, not yet a new standard.
Consolidation immunotherapy shows early promise in limited-stage SCLC
Consolidation immunotherapy after chemoradiotherapy looks promising in limited-stage SCLC, but awaits confirmation in a larger trial.
Cetuximab adds nothing to bevacizumab with FOLFOXIRI in colorectal cancer
When using FOLFOXIRI in metastatic colorectal cancer, bevacizumab is the better-tolerated partner, as cetuximab adds toxicity without efficacy here.
Catch immune-related adverse events early on checkpoint inhibitors
On checkpoint inhibitors, screen for immune-related events at every visit and, for anything beyond mild, hold the drug and start corticosteroids early.
An all-oral regimen extends control after CDK4/6 inhibition in breast cancer
After CDK4/6-inhibitor failure in ER-positive breast cancer, consider all-oral giredestrant–everolimus, especially in ESR1-mutated disease identified by testing at progression.
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