Patrick Forde · @FordePatrick“RAS(ON)i daraxonrasib in pretreated RAS mutant (non G12C) lung cancer, high grade tox in 54% incl 2.9% deaths. Tumor responses in 31-37% of pts, PFS 8.3m. So far not the breakthrough in lung cancer that it has been in pancreatic cancer #lcsm”
View post ↗See the full daraxonrasib NSCLC KOL discussion on KOL Pulse →Akeso announced that HARMONi-2 met its key secondary overall survival endpoint at a pre-specified interim analysis: ivonescimab monotherapy showed a statistically significant OS benefit over pembrolizumab in first-line PD-L1-positive NSCLC, with numeric results pending ahead of WCLC 2026. Separately, NEJM published the RMC-6236-001 results for daraxonrasib in previously treated RAS-mutant lung cancer: ORR of 31-37% across dose levels (31% at 120 mg or less, 34% at 160-220 mg, 37% at 300 mg), median PFS of 8.3 months in the docetaxel-naive 160-220 mg subgroup, and grade 3 or higher adverse events in 54% (NEJM, DCO 21-Jul-2025). A JTO study also suggests DNA and RNA EGFR variant allele fractions (VAF) can refine risk stratification in lung adenocarcinoma, identifying a low-risk group with a 5-year relapse rate of 11% regardless of stage. Ivonescimab is not approved by the US FDA for any indication: the FDA decision on ivonescimab plus chemotherapy in previously treated EGFR-mutant NSCLC (the HARMONi trial) is expected by November 14, 2026, and China's NMPA approved ivonescimab monotherapy for first-line PD-L1-positive advanced NSCLC in 2025 - the HARMONi-2 population, in the single-region Chinese trial that produced today's readout. Daraxonrasib is investigational in NSCLC - it is FDA-approved (RASONQUE) only in previously treated metastatic pancreatic cancer (Aug 2026); the Phase 3 NSCLC trial is RASolve 301.
“🎯VAF-based stratification: Low-risk group with 5-y relapse rate of only 11%, independent of stage”
— @HHorinouchi · EGFR VAF Risk Stratification · View post ↗
“😳Safety signals are notable: ~50% Gr 3 and several deaths on study. Tox is BIG issue for this class of drugs.”
— @TejasPatilMD · daroxonrasib toxicity · View post ↗
“Daraxonrasib in RAS-mutant NSCLC: promising activity, but toxicity deserves attention. In previously treated patients, response rates were 31–37%, with a median PFS of 8.3 months. However, grade ≥3 adverse events occurred in 54% of patients. An encouraging step for RAS-targeted therapy, with the efficacy–toxicity balance to watch closely.”
— @UOzkerim · Daraxonrasib NSCLC (NEJM) · View post ↗A review published in the journal Cancer (Cancer 2026;132:e70521) examines the challenges of applying circulating tumor DNA (ctDNA) in early breast cancer. Separately, discussion is highlighting the patient experience of living with metastatic breast cancer (MBC), fear of progression, and limited treatment options.
““Death is closer now, more immediate. I can feel its shadow in ways I couldn’t before.””
— @JaniceTNBCmets · Abigail (@AMJohnston1315), quoted by @JaniceTNBCmets · View post ↗📌 Amplified by @KolPulseAI
The Phase 3 TALENTACE trial in 342 patients with untreated TACE-eligible HCC met its primary endpoint, showing on-demand TACE plus atezolizumab/bevacizumab improved TACE-PFS to 11.30 months versus 7.03 months for TACE alone (HR 0.71). However, overall survival data is immature with no benefit shown to date (HR 0.96), and the primary endpoint was a non-conventional TACE-PFS, not RECIST-based PFS. This result mirrors EMERALD-1 and LEAP-012: both improved disease control over TACE alone, but neither converted it into an overall survival benefit at final analysis (EMERALD-1 HR 1.10, P=0.470, ESMO GI 2026; LEAP-012 closed after missing its OS endpoint) for adding an ICI/anti-VEGF combination to TACE. Atezolizumab/bevacizumab combined with on-demand TACE is investigational; the doublet is FDA-approved only as systemic first-line therapy in unresectable HCC (Lancet Gastro Hep, DCO 28-Feb-2025, first interim).
“TACE-PFS bundles local progression with re-treatment need, and the survival curves are still superimposed. We want the OS gain.”
— @DrAllanPereira · TALENTACE trial commentary · View post ↗📌 Amplified by @KolPulseAI
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The 2026 EAU Guidelines on NMIBC added a new recommendation for adding sasanlimab or durvalumab to BCG with maintenance in selected BCG-naive patients with high- and very-high-risk disease - advised with caution pending more mature data and within shared decision-making. Durvalumab plus BCG is FDA-approved in this setting (May 28, 2026, POTOMAC); sasanlimab remains investigational in the US. A separate SEER cohort analysis in T2N0M0 muscle-invasive bladder cancer (MIBC) showed lower 5-year overall survival with real-world trimodality therapy (TMT) compared to radical cystectomy (36.7% vs 62.6%), with commentators attributing the gap to patient selection, since SEER cannot capture trial-level eligibility.
“⚡️ 2026 EAU Guidelines on NMIBC: immune checkpoint inhibitors added to BCG in selected high- and very high-risk BCG-naïve patients.”
— @drenriquegrande · EAU NMIBC Guidelines · View post ↗
“Real-world TMT outcomes in this SEER cohort don't look like trial data. The likely reason: who got selected for it.”
— @katy_beckermann · Real-World TMT Outcomes · View post ↗The ongoing phase III DETER-SMM (EAA173) trial is evaluating the ongoing phase 3 DETER-SMM trial (EAA173, NCT03937635) comparing daratumumab plus lenalidomide/dexamethasone with lenalidomide/dexamethasone in high-risk smoldering myeloma, with overall survival as the primary endpoint. Other discussions center on clinical management, including the importance of acknowledging and mitigating infection risk with bispecific antibodies and the growing movement to reduce dexamethasone dosage (#downwithdex).
“#EAonc EAA173 - Daratumumab to Enhance Therapeutic Effectiveness of Revlimid in Smoldering Myeloma (DETER-SMM) - PI: @nsc_natalie”
— @mtmdphd · DETER-SMM trial · View post ↗
“I can tell that #downwithdex has made it in the myeloma world when it's starting to show up on CME-accredited slide decks 👏”
— @RahulBanerjeeMD · Dexamethasone reduction · View post ↗“Acknowledging Infection Risk in Bispecific Antibody Trials in the Treatment of Multiple Myeloma”
— @mtmdphd · Bispecific antibody safety · View post ↗
“A single-cell atlas of multiple myeloma defines malignant archetypes and proliferative states, identifying FCRL2 as a plasma-restricted or B cell-lineage-restricted surface target expressed by malignant plasma cells”
— @Myeloma_Doc · FCRL2 target · View post ↗The randomized phase 2 PARADIGM trial, published in the New England Journal of Medicine, showed improved event-free survival with azacitidine/venetoclax versus intensive induction chemotherapy in 172 fit, intensive-chemotherapy-eligible adults with newly diagnosed AML (median EFS 14.5 vs 6.2 months). Venetoclax in combination with azacitidine is FDA-approved for newly diagnosed AML only in adults aged 75 or older or with comorbidities precluding intensive induction chemotherapy; its use in fit, induction-eligible adults such as the PARADIGM population remains investigational. Other research highlighted includes studies on health-related quality of life after CAR T-cell therapy and a newly NIH-funded program (Mina Sedrak, MD, UCLA) that will test remotely delivered exercise plus senolytic therapy to reduce frailty after stem cell transplantation.
“We are entering a new frontier in AML ➡️The Paradigm study now out in @NEJM showing improved EFS in younger non-fav. risk AML Tx with Aza/Ven vs. Intensive chemo.”
— @LeukDocJZ · Paradigm Study in AML · View post ↗
“In a new study, Ajay Major (@majorajay), MD, MBA, and Vincenzo Pizzuti, MD, MS, have tracked a group of blood cancer patients using multiple surveys over the course of two years to see how CAR T-cell therapy impacts their health-related quality of life:”
— @CUCancerCenter · Quality of Life after CAR-T · View post ↗
“Was a great privilege to discuss in such a relaxed format varied strategies to improve transplant outcome in AML and the vital need for prospective trials.”
— @charliecraddock · Stem Cell Transplant in AML · View post ↗