Sarcoma Research Updates

In a phase 3 randomized self-controlled trial of mostly regorafenib-treated patients with unresectable colorectal cancer, GIST, or hepatocellular carcinoma, prophylactic hydrocolloid dressing plus standard moisturizing versus moisturizing alone reduced the incidence of grade ≥2 foot hand–foot skin reaction (20% vs 50%, p<0.0001) and delayed time to grade ≥2 HFSR (HR 0.32, p=0.0017), with lower patient-reported HFSR severity. The study supports hydrocolloid dressing as an effective prophylactic measure against HFSR in this population.

In a real-world review of 2,633 sarcoma cases under Japan's national CGP system (mean age 51.1 years, 45% female), three genomic panels were compared: GenMineTOP (DNA+RNA), FoundationOne CDx (DNA), and NCC Oncopanel (DNA). Potentially actionable alterations were found in 21.5% overall, and detection of actionable tyrosine-kinase fusions was higher with GenMineTOP (3.1% of 254) than with FoundationOne CDx (1.4% of 2,211) or NCC Oncopanel (0.6% of 168); GenMineTOP also identified rare NTRK fusions validated as oncogenic and sensitive to larotrectinib/entrectinib, though panels were applied to different patient groups so sensitivity and specificity remain undetermined.

Children with TP53-wild-type advanced hematologic and solid malignancies (n=22 enrolled, 20 treated) received ALRN-6924 as monotherapy or combined with cytarabine for leukemia; dose escalation reached 3.5 mg/kg without DLTs and one DLT occurred at 2.7 mg/kg. The regimen was generally tolerable (common treatment-related AEs included anemia and nausea), produced 30–50-fold increases in serum MIC-1 consistent with on-target p53 activation, and yielded one partial remission in a relapsed ALL patient on the combination arm; drug exposure was lower than in adults and an emergent TP53 mutation was detected in ctDNA from one Ewing sarcoma patient.