Key Points In a 3-year follow-up of the DASatinib versus Imatinib Study In treatment-Naive CML patients trial, first-line dasatinib resulted in faster and deeper responses compared with imatinib. Deeper responses at 3, 6, and 12 months were associated with better 3-year progression-free survival and overall survival.
Key Points• Imatinib-resistant/-intolerant patients with chronic myeloid leukemia in chronic phase can experience long-term benefit with dasatinib.• Early (3-and 6-month) molecular and cytogenetic responses were associated with improved progression-free survival and overall survival.We present long-term follow-up of a dasatinib phase 3 study of patients with imatinibresistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular response was achieved in 43% (100 mg once daily) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on £1%, >1% to 10%, and >10% BCR-ABL transcripts at 3 months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL £10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474. (Blood. 2014;123(15):2317-2324
Dasatinib was approved at 100 mg once daily for imatinib‐resistant or ‐intolerant patients with chronic myeloid leukemia (CML) in chronic phase, based on results of the phase 3 CA180‐034 (NCT00123474) study. Here we present the final 7‐year analysis of this pivotal study, the longest follow‐up to date of any second‐generation BCR–ABL1 tyrosine kinase inhibitor (TKI). Patients (n = 670) with imatinib‐resistant or ‐intolerant CML in chronic phase received dasatinib. Nineteen percent of patients continued on study treatment, with a greater proportion in the 100 mg once daily arm remaining on therapy. Seven‐year rates for major molecular response (MMR), progression‐free survival (PFS), and overall survival (OS) were similar across doses; MMR, PFS, and OS results were 46, 42, and 65% at 100 mg once daily, respectively. Improved PFS and OS rates were reported in patients who achieved BCR–ABL1 ≤10% at 3 and 6 months. No new safety signals were identified. The incidence of drug‐related pleural effusion was 28% at 100 mg once daily and 35% at the other three dose groups. Incidence of drug‐related pulmonary hypertension and pulmonary arterial hypertension remained low (≤3% across all doses). Arterial ischemic events occurred in ≤4% of patients across all doses. These data support the long‐term efficacy and well‐established safety profile of dasatinib for patients with imatinib‐resistant or ‐intolerant CML in chronic phase. Am. J. Hematol. 91:869–874, 2016. © 2016 Wiley Periodicals, Inc.
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.
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