Courtney Flaherty

Jonathan Trent, MD, discusses how proactive AE management, dose individualization, and liquid TKI formulations could improve treatment adherence and outcomes in GIST.

Callisia N. Clarke, MD, MS, FACS, FSSO, discusses how earlier alignment between surgeons and medical oncologists on systemic therapy use allows more patients to undergo resection.

Key Takeaways Dual OS endpoints split: ITT OS met significance, whereas the NLM subgroup missed (HR 0.83; 95% CI 0.66–1.05; P=.1185) despite median OS 15.9 vs 12.7 months. Trial design randomized 1:1 open-label against regorafenib after fluoropyrimidine/oxaliplatin/irinotecan, with mandated prior anti-EGFR for RAS wild-type tumors. Regulatory trajectory continues with an FDA-accepted NDA based on ITT OS, but the negative co-primary subgroup result raises interpretive risk absent alpha allocation and hierarchy disclosure. Safety in the NLM subgroup reportedly matched prior ITT experience with no new signals, though granular rates of grade ≥3 AEs, dose modifications, and discontinuations were not provided. Evidence gaps persist because NLM PFS/ORR/DOR and comprehensive subgroup analyses are pending conference submission, limiting assessment of benefit heterogeneity by liver-metastasis status. SHOW MORE

R. Lor Randall, MD, FACS, reviews a longitudinal study in osteosarcoma showing a strong correlation between ctDNA status and clinical outcomes like EFS.

The CHMP has recommended datopotamab deruxtecan for patients with first-line metastatic TNBC who are not candidates for immunotherapy.

Key Takeaways FDA issued a CRL for LNTH-2501 due to unresolved third-party manufacturing inspection conditions, with no cited safety, efficacy, or clinical data deficiencies. Phase 1/2 NCT01619865 showed Ga-68 edotreotide PET/CT achieved ~90% positive and 86%–89% negative agreement versus reference standards, outperforming Octreoscan SPECT plus contrast CT. In phase 2 NCT01869725, PET/CT demonstrated 90%–92% positive and 75% negative percent agreement against composite reference, in 59 evaluable patients with NETs or other SSTR-positive tumors. LNTH-2501 would ship as a two-vial radiopharmacy kit enabling on-site preparation of Ga-68 edotreotide from generator eluate for PET localization of SSTR-positive NETs. SHOW MORE

Key Takeaways Tisotumab vedotin improves OS vs chemotherapy in 2L recurrent/metastatic cervical cancer (HR 0.70) but tolerability issues—fatigue, neuropathy, mandated ophthalmology—may limit durability as newer ADCs emerge. Mirvetuximab soravtansine adoption is expanding into moderate FRα expression and post-PARP settings; adding bevacizumab is used to augment activity, while skepticism persists about framing ADC continuation as “maintenance.” Rina-S, LY4170156, and AZD5335 demonstrate 31%–56% ORRs in platinum-resistant ovarian cancer, raising questions about whether bystander effect/payload delivery will render future FRα ADCs increasingly biomarker-agnostic. In endometrial cancer, sacituzumab govitecan (ASCENT-GYN-01) and sac-TMT (TroFuse-005 positive OS/PFS topline) may compete, with adoption influenced by diarrhea/neutropenia vs mucositis and community familiarity. CDH6-targeted R-DXd shows 44%–57% ORRs in platinum-resistant ovarian cancer with rare adjudicated grade 3 ILD; deruxtecan-class ILD vigilance is essential, especially in combination trials. SHOW MORE

Need a refresh on the current regulatory landscape for GI oncology? We've got you covered. Here's everything that moved the needle across GI malignancies this month.

Key Takeaways Daraxonrasib targets active RAS rather than GDP-bound RAS, addressing PDAC's predominant KRAS G12D/G12V/G12R biology and expanding beyond allele-restricted paradigms such as KRAS G12C. Phase 1/2 monotherapy signals in pretreated RAS-mutant PDAC included ORR ~29%–35%, DCR up to 95%, median PFS 8.5 months, and median OS 13.1 months at 300 mg daily. RASolute 302 demonstrated median OS 13.2 vs 6.6 months in RAS G12–mutant disease (HR 0.40) with improved PFS (7.3 vs 3.5 months) and higher ORR (33.2% vs 11.8%). Patient-reported pain and global QOL deterioration were delayed versus chemotherapy, with manageable toxicity dominated by rash and stomatitis; 42% remained on daraxonrasib at cutoff versus 14% on chemotherapy. Clinical strategy is expanding into frontline and adjuvant PDAC phase 3 trials, additional registrational studies in RAS-mutant solid tumors, and rational combinations while anticipating resistance mechanisms and sequencing challenges. SHOW MORE

Key Takeaways Daraxonrasib targets active RAS-GTP via a cyclophilin A tricomplex, broadly inhibiting mutant and wild-type KRAS/NRAS/HRAS and addressing G12D/G12V/G12R-dominant PDAC. RASolute 302 showed median OS 13.2 vs 6.6 months (HR 0.40) and median PFS 7.3 vs 3.5 months, with ORR ~33% vs ~12%. Patient-reported pain and global QOL deterioration were delayed versus chemotherapy, and most TRAEs were low-grade dermatologic/GI events; rash and stomatitis were key dose-reduction drivers. Phase 1/2 signals supported durability, including ORR 47% with monotherapy and 58% with gemcitabine/nab-paclitaxel; MTAP-deleted tumors showed 92% ORR with added PRMT5 inhibition. Ongoing registrational programs include frontline RASolute 303, adjuvant RASolute 304, and NSCLC RASolve 301; FDA priority voucher, breakthrough/orphan designations, and expanded access accelerate near-term integration. SHOW MORE