Pemetrexed Maintenance Therapy Following Induction Therapy in Advanced NSCLC: Results of the Phase III PARAMOUNT Trial
According to a study in the February 16 online issue of The Lancet Oncology by Paz-Ares and associates, continuation of pemetrexed (Alimta, Eli Lilly) as maintenance therapy significantly reduced the risk of disease progression and was well tolerated in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) who had not progressed after induction therapy with pemetrexed plus cisplatin. In the randomized, double-blind, multicenter phase III PARAMOUNT (Phase III Study of Maintenance Pemetrexed [pem] Plus Best Supportive Care [bsc] Versus Placebo Plus bsc Immediately Following Induction Treatment With Pem Plus Cisplatin for Advanced Nonsquamous Non-Small Cell Lung Cancer [NSCLC]) trial, patients with advanced nonsquamous NSCLC received standard induction therapy with 4 cycles of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on a 21-day cycle. Of the 939 patients who received induction therapy, 539 patients who did not progress and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were subsequently randomized to maintenance therapy with either pemetrexed (500 mg/m2 on day 1 of a 21-day cycle) plus best supportive care (359 patients) or placebo plus best supportive care (180 patients) until disease progression. Progression-free survival (PFS) was the primary endpoint. Patients who received pemetrexed maintenance therapy had a significant reduction in the risk of disease progression compared to patients who received a placebo (hazard ratio [HR] 0.62; 95% confidence interval [CI], 0.49–0.79; P<.0001). Median PFS was 4.1 months for the pemetrexed arm versus 2.8 months for the placebo arm. Grade 3/4 adverse events that occurred more commonly in the pemetrexed group versus the placebo group were anemia (4% vs <1%), neutropenia (4% vs 0%), and fatigue (4% vs <1%). Patients in the pemetrexed group experienced more grade 3/4 adverse events (9%) than patients in the placebo group (1%). There were 19 patients (5%) in the pemetrexed treatment group and 6 patients (3%) in the placebo group who discontinued treatment due to drug-related adverse events.
Origin of Acute Myeloid Leukemia Linked to Founding Clones and Subclones that Cause Myelodysplastic Syndromes
In order to identify the somatic mutation specific to secondary acute myeloid leukemia (AML), Walter and colleagues performed whole-genome sequencing of 7 paired samples of skin and bone marrow in 7 patients with secondary AML. To establish whether the specific somatic mutations were present at that stage, the investigators then genotyped marrow samples obtained during the antecedent myelodysplastic syndrome (MDS) stage from each patient. The entire clonal structure of each pair of samples from the MDS to the AML stage was analyzed in order to identify recurrent mutations. Regardless of the myeloblast count, there was an approximate 85% clonality between MDS and AML cells from paired bone marrow samples. An antecedent founding clone was observed in each case, containing 182–660 somatic mutations. A new subclone with hundreds of new mutations was also observed to be emerging from the founding clone. At least 1 mutation in a coding gene was present in all founding clones and subclones. Published in the March issue of The New England Journal of Medicine, the study results suggest that AML evolves from the cells that cause MDS after these cells have undergone multiple cycles of mutations and clonal selection.
Helicobacter Pylori Eradication Therapy in Early-Stage Gastric Diffuse Large B-Cell Lymphoma
Kuo and coworkers evaluated the efficacy of Helicobacter pylori eradication (HPE) therapy in early-stage gastric diffuse large B-cell lymphoma (DLBCL) without features of mucosa-associated lymphoid tissue (MALT), known as pure (de novo) DLBCL, compared with its efficacy in high-grade transformed tumors (DLBCL with features of MALT; DLBCL[MALT]). The study included 50 patients with stage IE/IIE1, H. pylori–positive gastric DLBCL with frontline HPE. Of the 16 de novo DLBCL patients, 100% experienced successful eradication of H. pylori infection, compared with 32 of the 34 DLBCL(MALT) patients (94.1%). Complete pathologic remission (pCR) following HPE occurred in 68.8% (11/16) of patients with de novo DLBCL and in 56.3% (18/32) of patients with DLBCL(MALT). The median time-to-pCR was 2.1 months for de novo DLBCL patients versus 5 months for DLBCL(MALT) patients (P=.024). With the exception of 1 patient with de novo DLBCL who died of lung cancer, all patients with pCR after HPE were alive and free of lymphoma at a median follow-up of 7.7 years. Results from this explorative study, which were published in the March 7 online issue of Blood, showed that a significant portion of early-stage, H. pylori–positive gastric de novo DLBCL is H. pylori–dependent and responds to antibiotic treatment. Future prospective studies should be considered in order to validate these findings.
By Stacey Small