Overall survival extrapolations in Swedish TLV oncology appraisals from 2009 to 2019 were often conservative for the active arm. Reapplying the original extrapolation assumptions to longer follow-up data (average 54.2 months versus 28.1 months originally) raised the average area under the survival curve by 8.8% under TLV assumptions and 10.9% under manufacturer assumptions, with material increases above 10% in roughly one-third of cases. The findings argue for revisiting survival model fit and assumptions as longer-term data emerge.
Why it matters: Shows that roughly one-third of Swedish HTA survival extrapolations materially underestimated long-term OS, informing cost-effectiveness methods.
At the 2026 SOHO annual meeting, Jasmine M. Zain of Memorial Sloan Kettering described how to attribute secondary T-cell malignancies to CAR-T therapy, requiring clonality flow cytometry, PCR detection of the CAR vector in the tumor genome, and insertion-site analysis relative to proto-oncogene or tumor suppressor promoters, with a theoretical risk window of 300 base pairs. David Sallman covered lower-risk MDS updates including luspatercept for ring sideroblast patients, the recent FDA approval of imetelstat, and eprenetapopt plus azacitidine data in TP53-mutated higher-risk MDS. Julie M. Vose reviewed the CLL landscape, from first-generation ibrutinib to better-tolerated second-generation BTK inhibitors acalabrutinib and zanubrutinib, approved pirtobrutinib in relapsed or refractory disease, and bispecific CD20xCD3 antibodies and lisocabtagene maraleucel under study.
Iberdomide plus daratumumab and dexamethasone significantly improved MRD-negative complete response versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma in the phase 3 EXCALIBER-RRMM trial. The most common grade 3 or 4 adverse events were haematological events and infections, mostly manageable with standard supportive care. The findings support this combination as an efficacious option across diverse care settings.
Half of multiple myeloma patients in Cohort A of the Phase 2 CARTITUDE-2 study remained alive and progression-free after a single dose of Carvykti, with a median follow-up of 60.7 months. Of 20 patients treated after one to three prior lines of therapy, 10 were alive without progression, and overall survival at this timepoint was 69.2%. The data extend evidence for the BCMA-targeting CAR T therapy in earlier-line use, where Gilead's anito-cel awaits an FDA decision on Dec. 23.
Genentech will pay Earendil Labs $55 million upfront to discover and develop several bispecific antibody cancer therapies, in a deal that could exceed $1.5 billion including milestones, plus tiered royalties. Earendil leads antibody discovery and early clinical research on pre-agreed target combinations, while Genentech handles global development and commercialization; oncology indications have not been named. Roche also struck a $70 million upfront deal with Atavistik Bio the same day.
A single infusion of CARVYKTI (cilta-cel) kept 10 of 20 patients (50%) with relapsed/refractory multiple myeloma alive and progression-free at five years without maintenance therapy. The CARTITUDE-2 cohort A data, with a median follow-up of 60.7 months, cover patients who had received 1 to 3 prior lines of therapy. The results extend the durability evidence for cilta-cel into earlier-line RRMM.
A Cell study proposes a mechanism for an executor protein in cuproptosis, the copper-dependent form of cell death. Prior work showed copper ionophores carry copper into cells, causing lipoylated mitochondrial proteins to aggregate and iron-sulfur cluster proteins to break down, but no executor protein had been identified, unlike Gasdermin in pyroptosis, Caspases in apoptosis, and RIPK3 and MLKL in necroptosis. The work points to intervention strategies for drug-resistant gastric cancer and liver cancer.
Aurora kinase A maintains global DNA methylation in prostate cancer cells by phosphorylating the epigenetic regulator UHRF1 at Ser76, which blocks its polyubiquitination and degradation by the proteasome. Depleting AURKA lowered genomic 5methylcytosine levels, destabilized UHRF1, de-repressed p16 and p21, and impaired cell proliferation; only wild-type UHRF1, not the phospho-deficient S76A mutant, rescued these defects. The work links oncogenic kinase signaling directly to DNMT1-mediated methylation maintenance and identifies a druggable AURKA-UHRF1 axis in prostate cancer.
Why it matters: It connects a well-known kinase to the DNA methylation machinery, defining a phosphorylation-dependent mechanism that prostate cancer cells depend on.
Structure-based design of quinazoline analogues incorporating an intramolecular hydrogen bond at the 5-position yielded potent inhibitors of EGFR exon 20 insertion mutants in non-small cell lung cancer. Thirty-six compounds were synthesised and tested in biochemical kinase assays; the R-configuration of the 5-position acylpyrrolidine substituent plus specific 4-position anilines gave the best activity. The most potent analogues reached sub-nanomolar IC50 values against various EGFR exon20ins mutants.
Earlier infusions of first-line platinum-etoposide plus atezolizumab or durvalumab were linked to longer survival in 107 patients with extensive-stage small cell lung cancer. Those treated before the cohort median time of day of administration (11:54) had median PFS of 9.07 vs. 7.23 months and OS of 21.17 vs. 11.43 months, with adjusted HRs of 1.63 and 1.65 for later administration, and no difference in toxicity. The finding points to infusion timing as a modifiable factor that warrants prospective testing.
AXL and PD1 inhibition with bemcentinib plus pembrolizumab met its primary endpoint in the phase IIA MIST3 trial in ICB naïve-relapsed mesothelioma, with a 12-week disease control rate of 46.2% (90% CI 29.2-63.8%); grade 3 or greater adverse events occurred in 53.9% of patients. Multiomic analyses linked response to NF2 loss, immune response signalling, epithelial mesenchymal transition, and neutrophil-related transcriptional programmes including SPI1, ETS2 and FLI1 activation. Gut microbiota composition differed between responders and non-responders and correlated with neutrophil-associated transcription programmes, IRF3 and TLR2.
Tissue-resident macrophages enriched at the tumor boundary deliver the selenoprotein Selenop to highly invasive pancreatic ductal adenocarcinoma cells, helping them evade ferroptosis and maintain their invasive state. The finding reframes immune cells in the tumor microenvironment as nutrient and metabolic donors that directly sustain malignant cell behavior, not only as sources of cytokines and immune signals.
Pancreatic ductal adenocarcinoma frequently spreads to the liver, and about 40% of PDAC tumors lack PHGDH, the rate-limiting enzyme of de novo serine synthesis, making them dependent on external serine. Analysis of human PDAC liver metastasis specimens showed marked upregulation of PHGDH in surrounding hepatocytes, and a mouse liver metastasis model confirmed that PHGDH-deficient pancreatic cancer cells activate the serine synthesis pathway in neighboring hepatocytes.
An FDA expert committee voted on September 23 that the clinical benefits of Galleri, a multi-cancer early-detection blood test, outweigh its risks. The vote marks a key step toward formal FDA review of the product, which is positioned as a blood draw for early cancer screening. The agency's decision process now moves forward following the panel's endorsement.
A Zhejiang University team publishing in Nature used a phosphoproteomics screen to identify MFF as a regulator of ferroptosis, tracing how mitochondrial and peroxisome dynamics jointly govern execution of this cell-death pathway. The work ran from omics screening through in vivo pharmacological validation and offers a reusable target-screening framework for ferroptosis-centered cancer research.
A research team developed a senescence-targeted nanotherapy that ameliorated fibrosis and overcame immune exclusion in cancer in mouse models. The study was published in Science.
A study found that ceramide synthesis drives colorectal cancer metastasis, with a mechanism involving activation of a regenerative program by the YAP signaling pathway. The study was published in Science.
Why it matters: The study reveals a new mechanism by which the sphingolipid metabolite ceramide promotes colorectal cancer metastasis, suggesting a potential direction for targeting the tumor microenvironment.
FDA advisors have voted to recommend Grail's multi-cancer blood test Galleri, despite a major trial setback earlier this year and ongoing questions over its efficacy. Grail now awaits an FDA decision on the test. The outcome leaves the company positioned for a potential approval ahead.
Adding the CD47 inhibitor evorpacept to trastuzumab, ramucirumab and paclitaxel (TRP) produced a higher objective response rate than TRP alone in patients with HER2-positive advanced gastric cancer that had progressed on anti-HER2 treatment. The finding comes from the phase 2 part of the randomized ASPEN-06 trial. Response was associated with CD47 and HER2 expression.
An FDA advisory panel endorsed Galleri, Grail's blood test to screen for multiple types of cancer, voting 10 to 0 that there is reasonable assurance the test is safe. The panel split 6 to 4 on effectiveness and voted 7 to 2 with one abstention that benefits outweigh risks for patients meeting the proposed indication's criteria. The FDA is not obliged to follow the panel's advice but often does.
