The edition · Oncology
Venetoclax added to DA-EPOCH-R killed more patients than it helped
A randomised phase 2 trial in double-hit lymphoma closed early for excess mortality, dose-escalated radiotherapy improves ten-year progression-free survival in high-risk prostate cancer, and ivonescimab extends progression-free survival after EGFR-TKI failure without a clear survival gain.
The edition in brief
ALLIANCE A051701 randomised 73 patients with newly diagnosed double-hit lymphoma to DA-EPOCH-R with or without venetoclax. The cohort closed early. On-treatment deaths were 1 of 36 without venetoclax and 6 of 37 with it, four from sepsis. Progression-free survival did not improve (HR 1.13, 95% CI 0.53 to 2.37), and 24-month overall survival was 72% versus 52% (HR 2.49, 95% CI 1.03 to 6.04, p=0.038). A biologically rational combination made outcomes worse. GETUG AFU 18 randomised 505 men with high-risk prostate cancer on long-term androgen deprivation to 80 Gy or 70 Gy. At a median 9.5 years, ten-year progression-free survival was 83.6% versus 72.2% (HR 0.56, 95% CI 0.40 to 0.78). Grade 3 or worse acute and late toxicity were essentially identical between arms. HARMONi randomised 438 patients with EGFR-mutated non-small-cell lung cancer progressing after a third-generation TKI to ivonescimab or placebo with pemetrexed and carboplatin. Median progression-free survival was 6.8 versus 4.4 months (HR 0.52, 95% CI 0.41 to 0.66), but overall survival was 16.8 versus 14.0 months with a confidence interval crossing 1.0. Serious treatment-related adverse events nearly doubled, 28% versus 15%. EMERALD-3 added durvalumab-tremelimumab with or without lenvatinib to transarterial chemoembolisation in hepatocellular carcinoma: progression-free survival improved from 9.8 to 13.0 months, overall survival did not yet differ, and serious adverse events rose from 23% to 64%. The ACG has published updated guidance on adenomatous colorectal polyposis syndromes. Today's pearl: a progression-free survival gain with unchanged overall survival is a claim about scans, not about life.
Venetoclax plus DA-EPOCH-R in double-hit lymphoma: stopped early for excess deaths
Do not add venetoclax to DA-EPOCH-R in double-hit lymphoma — the trial closed early with six on-treatment deaths against one, mostly from sepsis, and no efficacy gain.
GETUG AFU 18: 80 Gy beats 70 Gy in high-risk prostate cancer, without extra toxicity
Escalate to 80 Gy in high-risk prostate cancer on long-term androgen deprivation — it improves ten-year progression-free survival from 72% to 84% with no measurable increase in serious toxicity.
A progression-free survival gain with flat overall survival is a claim about scans
When discussing a drug that improved progression-free survival without changing overall survival, say plainly that it delays what the scan shows and increases time on treatment — and let the patient weigh that against certain toxicity.
HARMONi: ivonescimab delays progression after EGFR-TKI failure; survival is not yet there
Adding ivonescimab to chemotherapy after EGFR-TKI failure buys about 2.4 months before progression, at the cost of nearly double the serious adverse events, with no proven survival gain yet.
EMERALD-3: immunotherapy with TACE delays progression in hepatocellular carcinoma at a real toxicity cost
Adding durvalumab and tremelimumab to TACE extends progression-free survival by about three months in hepatocellular carcinoma, but adding lenvatinib on top mainly adds toxicity without clear extra benefit.
ACG updates its guidance on adenomatous colorectal polyposis syndromes
New ACG guidance on adenomatous polyposis syndromes is out — and the recurring practical failure it addresses is stopping surveillance after colectomy, when duodenal and ampullary risk remains.
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