64 research outputs found
Outcomes of patients with advanced cancer and KRAS mutations in phase I clinical trials.
BackgroundKRAS mutation is common in human cancer. We assessed the clinical factors, including type of KRAS mutation and treatment, of patients with advanced cancer and tumor KRAS mutations and their association with treatment outcomes.MethodsPatients referred to the Phase I Clinic for treatment who underwent testing for KRAS mutations were analyzed.ResultsOf 1,781 patients, 365 (21%) had a KRAS mutation. The G12D mutation was the most common mutation (29%). PIK3CA mutations were found in 24% and 10% of patients with and without KRAS mutations (p<0.0001). Of 223 patients with a KRAS mutation who were evaluable for response, 56 were treated with a MEK inhibitor-containing therapy and 167 with other therapies. The clinical benefit (partial response and stable disease lasting ≥6 months) rates were 23% and 9%, respectively, for the MEK inhibitor versus other therapies (p=0.005). The median progression-free survival (PFS) was 3.3 and 2.2 months, respectively (p=0.09). The respective median overall survival was 8.4 and 7.0 months (p=0.38). Of 66 patients with a KRAS mutation and additional alterations, higher rates of clinical benefit (p=0.04), PFS (p=0.045), and overall survival (p=0.02) were noted in patients treated with MEK inhibitor-containing therapy (n=9) compared to those treated with targeted therapy matched to the additional alterations (n=24) or other therapy (n=33).ConclusionsMEK inhibitors in patients with KRAS-mutated advanced cancer were associated with higher clinical benefit rates compared to other therapies. Therapeutic strategies that include MEK inhibitors or novel agents combined with other targeted therapies or chemotherapy need further investigation
A phase 2, open-label study of the combination of spartalizumab (PDR001) and LAG525 for patients with advanced solid tumors and hematologic malignancies.
Uveal melanoma patients (pts) treated with abbv-075 (mivebresib), a pan-inhibitor of bromodomain and extraterminal (BET) proteins: Results from a phase 1 study.
A phase 1, multicenter, dose-escalation study of PRN1371, an irreversible covalent FGFR1-4 kinase inhibitor, in patients with advanced solid tumors, followed by expansion cohorts in patients with FGFR genetic alterations.
Pembrolizumab (MK-3475) for patients (pts) with advanced esophageal carcinoma: Preliminary results from KEYNOTE-028.
Updated results for the advanced esophageal carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab.
T-cell inflamed phenotype gene expression signatures to predict clinical benefit from pembrolizumab across multiple tumor types.
Safety/efficacy of MK-8669 (ridaforolimus) plus MK-2206 (AKT inhibitor) in patients with advanced breast cancer with low RAS signature and PTEN deficient prostate cancer.
Biomarker-Directed Therapy of Squamous Carcinomas of the Head and Neck: Targeting PI3K/PTEN/mTOR Pathway
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