Top 5 Papers
#1
Source: Annals of Oncology | Authors: Liu R, Xu J, et al. — multicenter, 51 sites in China | Published: 2026 (PMID 41571045)
Score: 12/20 — Ann Oncol base (7) + Phase III RCT (+3) + OS + PFS benefit (+2) = 12.
Pre-specified interim of a randomized Phase III in 188 previously treated HER2-positive advanced gastric/GEJ adenocarcinoma patients. Anbenitamab — a novel anti-HER2 × anti-HER2 bispecific binding two distinct ECD epitopes — plus chemotherapy crushed chemo alone: median PFS 7.1 vs 2.7 months (HR 0.25, 95% CI 0.17–0.39, p<0.0001), median OS 19.6 vs 11.5 months (HR 0.29, 95% CI 0.17–0.50, p<0.0001). Grade ≥3 TRAEs were higher (60% vs 45%) but there were ZERO treatment-related deaths in the anbenitamab arm versus 5 in the control arm. This is one of the most dramatic 2L HER2+ gastric Phase III hazard ratios ever reported.
Post angle: An HR of 0.25 for PFS in 2L HER2+ gastric is jaw-dropping — anbenitamab’s dual-epitope bispecific design appears to overcome trastuzumab-resistant tumors that defeated T-DXd in later lines. China-only data, 51 sites, but the effect size demands a global confirmatory trial. #GastricCancer #HER2 #Bispecific
#2
Source: Annals of Oncology | Authors: Janjigian YY, Moehler M, et al. — CheckMate 649 investigators (global) | Published: 2026 (PMID 41687718)
Score: 12/20 — Ann Oncol base (7) + Phase III RCT (+3) + sustained OS benefit (+2) = 12.
First-ever 5-year survival update from CheckMate 649 (n=1,581 HER2-negative G/GEJ/esophageal adenocarcinoma). At minimum 60.1-month follow-up, nivolumab + chemotherapy in PD-L1 CPS≥5 patients delivered OS HR 0.71 (95% CI 0.61–0.81), 5-year OS 16% vs 6% in chemo alone, and 5-year PFS 10% vs 6%. Benefits were maintained across CPS≥1, CPS≥10, and all-randomized populations. No new safety signals. This is the longest-term randomized data for any PD-1 + chemo combination in this indication — and the 5-year OS difference (16% vs 6%) means nearly 3× the number of long-term survivors.
Post angle: Five years out, CheckMate 649 still delivers — 16% of CPS≥5 patients alive at year 5 on nivo+chemo vs 6% on chemo alone. For a disease where median OS was historically ~11 months, having 1-in-6 patients still alive at 5 years is the new yardstick. #GastricCancer #Immunotherapy
#3
Source: Journal of Clinical Oncology | Authors: Chen B, Xi M, et al. — multicenter (4 hospitals, China) | Published: 2026 (PMID 41962116)
Score: 12/20 — JCO base (8) + Phase II (+2) + OS benefit (+2) = 12.
Randomized Phase II in 114 patients with unresectable stage II–IVB esophageal squamous cell carcinoma. All received paclitaxel/cisplatin induction + concurrent CRT + tislelizumab. Group A got 16 cycles of tislelizumab (with 12 maintenance cycles); Group B got just 4 cycles (no maintenance). The surprise: Group B (no maintenance) hit 1-year PFS of 71.9% with HR 0.54 (95% CI 0.32–0.94) and OS HR 0.42 (95% CI 0.22–0.82) versus historical control — while Group A (with maintenance) had a PFS HR of 1.06, i.e., no benefit at all. Grade ≥3 AEs ran 80.7% vs 86.0%. This challenges the dogma that longer immunotherapy maintenance is always better.
Post angle: EC-CRT-002 is the rare trial that argues LESS immunotherapy is better. Maintenance tislelizumab in unresectable ESCC delivered the toxicity but not the survival benefit — short course (no maintenance) was the winner. Practice question: are we over-treating ESCC patients globally? #EsophagealCancer #Immunotherapy
#4
Source: Journal of Clinical Oncology | Authors: de la Fouchardière C, Coutzac C, et al. — multicenter (France) | Published: 2026 (PMID 41980235)
Score: 11/20 — JCO base (8) + Phase II (+2) + biomarker-guided/dMMR (+1) = 11.
Phase II IMHOTEP enrolled 81 patients with dMMR/MSI localized colorectal cancer (71% stage III) for perioperative pembrolizumab (400 mg q6w × 1–2 neoadjuvant cycles, then up to 1 year total). The pathologic complete response rate was 52.7% (95% CI 41–64%, 38/72 resected). An unplanned exploratory analysis showed pCR after 2 neoadjuvant cycles was 68.2% versus 46.0% after only 1 cycle (p=0.0125) — a dose-response that supports going deeper before surgery. At 24.5-month median follow-up only 3 recurrences had occurred. Grade ≥3 immune AEs were 15.7%, including 1 grade 5 myasthenia gravis. NICHE-2 and PICC opened this door in non-randomized cohorts; IMHOTEP brings randomized prospective evidence and a clean cycle-number signal.
Post angle: IMHOTEP confirms what NICHE-2 hinted at — dMMR localized CRC is the ideal substrate for perioperative IO. Two neoadjuvant cycles of pembro yield 68% pCR vs 46% after one. The looming question: in dMMR CRC, can we declare organ preservation after pCR and skip surgery altogether? #CRC #dMMR #PrecisionMedicine
#5
Source: JAMA Internal Medicine | Authors: Verma M, Navarro V, et al. — 19 US medical centers (Duke coordinating) | Published: 2026-06-01 (PMID 41973444)
Score: 11/20 — Tier-1 adjacent base (7) + Cluster RCT (+3) + practice-changing care delivery model (+1) = 11.
Cluster RCT across 19 US medical centers (n=935 adults with decompensated cirrhosis or hepatocellular carcinoma, life expectancy ≥6 months, not transplanted). Eleven centers had hepatologists trained in primary palliative care deliver four structured visits over 3 months; 8 centers used palliative care specialists. Quality-of-life improved meaningfully in both arms (FACT-Hep change: hepatologist 8.01 vs consultative 7.02, both p<0.001). Pre-specified non-inferiority of the hepatologist arm was met (adjusted difference 0.98, 95% CI −2.86 to 4.83, p=0.01). Symptom burden and depression improved comparably in both. Patient satisfaction was statistically HIGHER with hepatologists (3.37 vs 0.91, p=0.002). Mortality was equivalent. Given how few HCC and ESLD patients ever see formal palliative care, a hepatologist-delivered model could close a massive access gap.
Post angle: Palliative care for HCC and end-stage liver disease is a known access gap — most patients never get a referral. This 935-patient cluster RCT shows trained hepatologists deliver it just as effectively as PC specialists — and patients are MORE satisfied with their hepatologist. Workforce solution to a real problem. #HCC #PalliativeCare #Hepatology
Additional Papers of Interest
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Journal of Gastroenterology — In the landmark JASPAC-01 trial (Japanese SOC adjuvant after curative resection), 117 of 187 patients (63%) were overdosed when calculated by BSA alone vs the renal-function-adjusted formula; the overdose group had higher anemia (grade ≥3: 18.8% vs 4.7%) and worse 5-year OS (41.9% vs 47.6%). Real-world implication: use the formula.
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Diabetes Care — 46 observational studies, N=7,124,845. Thiazolidinediones associated with LOWEST HCC incidence vs DPP-4 inhibitors (HR 0.50), GLP-1RAs (HR 0.72), insulin (HR 0.20), sulfonylureas (HR 0.69). SGLT2 inhibitors lowest for cirrhosis and liver-related mortality; GLP-1RAs lowest for decompensation. Observational — RCTs needed — but a useful signal for hepatologists managing T2DM + MASLD.
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European Journal of Surgical Oncology — 6 retrospective studies. At 1 and 3 years OS was similar, but at 5 years LT had a significant survival advantage (OR 0.55, p=0.002) and far lower recurrence (RFS OR 0.40, p<0.001). Selection bias is real, but the data argue for considering LT in carefully selected cHCC-CCA patients rather than reflex resection.
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Cancer Medicine — Pooled pre-diagnosis weight loss in pancreatic cancer averaged 5.9 kg (95% CI 4.7–7.1) and BMI change −2.5 kg/m² (95% CI −3.0 to −2.1). High heterogeneity, but a usable reference for clinical risk stratification and earlier-detection algorithms in primary care.
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Clinical and Translational Science — 46 patients across CRC, gastric, NSCLC, pancreatic, TNBC. No PR or CR by RECIST; 32.6% stable disease. 45.7% grade ≥3 drug-related TEAEs, dominated by transaminitis. Translational work suggests on-target hepatocyte toxicity (not Kupffer cells) limits the therapeutic window. Cautionary tale for DR5/TRAIL pathway drugging.
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