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Given the abundance of new research, it can be challenging to stay current on the latest advancements and findings. Oncology Times offers summaries of the newest studies to ensure you are up-to-date on the latest innovations in oncology practice.

 

CHRONIC MYELOID LEUKEMIA

Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial

New research showed patients with chronic myeloid leukemia (CML) treated with bosutinib had better major molecular response and complete cytogenic response rates compared with those who were treated with imatinib (J Clin Oncol 2017; doi:10.1200/JCO.2017.74.7162). The ongoing, multinational, phase III study randomly assigned 536 patients with newly diagnosed chronic-phase CML 1:1 to receive 400 mg of bosutinib once daily (n=268) or imatinib (n=268). Researchers excluded patients with Philadelphia chromosome-negative BCR-ABL1-positive and unknown Philadelphia chromosome status. Additionally, individuals with atypical BCR-ABL1 transcript type were not included. Data showed that patients treated with bosutinib had significantly higher major molecular response rates at 12 months compared with those who received imatinib (47.2% vs. 36.9%; P = .02). Patients in the bosutinib group also had a higher complete cytogenic response rate (77.2% vs. 66.4%; P = .0075). In addition, investigators reported that patients treated with bosutinib had a favorable cumulative incidence (major molecular response, HR = 1.34; P = .0173; complete cytogenic response; HR = 1.38; P < .001) and earlier response times. "Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib," study authors concluded. "Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML."

 

ERK1/2 INHIBITORS

First-in-class ERK1/2 inhibitor ulixertinib (BVD-523) in patients with MAPK mutant advanced solid tumors: results of a phase I dose-escalation and expansion study

The novel ERK1/2 kinase inhibitor ulixertinib displayed an acceptable safety profile and had clinical activity in patients whose tumors had mutations in the MAPK cell-signaling pathway, according to recent data (Can Discov 2017; doi:10.1158/2159-8290.CD-17-1119). Researchers tested the ERK inhibitor ulixertinib in an open-label, first-in-human study. Twenty-seven patients were enrolled in the dose-escalation phase and 108 in the dose-expansion phase. All patients had advanced solid tumors, and more than 65 percent had BRAF-mutant cancers. Of the patients, 24 percent had received prior BRAF and/or MEK therapy and 51 percent had received prior immunotherapy. In the dose-escalation phase, the recommended phase II dose (RP2D) of ulixertinib was determined to be 600 mg twice daily. The dose-expansion portion of the trial tested the RP2D of ulixertinib in six groups of patients whose tumors had BRAF, NRAS, or MEK mutations, the majority of whom were not treated with prior MAPK-targeted therapy. Partial responses (PR) were seen in 12 percent and 14 percent of evaluable patients in the dose-escalation and dose-expansion cohorts, respectively. PR and/or disease stabilization was seen in all groups, including solid tumors with atypical BRAF mutations. Patients treated at the RP2D had near-complete inhibition of ERK as verified in blood samples. Side effects were comparable to other MAPK inhibitors, and the most common treatment-related adverse event (AE) was rash. No AEs above grade 3 were observed, according to investigators. "Ulixertinib has an acceptable safety profile with favorable pharmacokinetics and has shown early evidence of clinical activity in NRAS- and BRAF V600- and non-V600-mutant solid-tumor malignancies," study authors noted.

 

PANCREATIC CANCER

Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer

A new study pinpoints the inverse correlation between a known oncogene and the expression of an oncosuppressor microRNA as the reason for extended pancreatic cancer survival (Nat Comm 2018; doi:10.1038/s41467-017-02283-9). The study may serve as a basis for the development of an effective cocktail of drugs for this deadly disease and other cancers, according to investigators. The research team examined pancreatic cancer cells and discovered an inverse correlation between the signatures of miR-34a, a tumor suppressant, and PLK1, a known oncogene. The levels of miR-34a were low in pancreatic cancer mouse models, while the levels of the oncogene were high. This correlation made sense for such an aggressive cancer, but to confirm the same was true in humans the scientists performed RNA profiling and analysis of samples taken from pancreatic cancer patients. The molecular profiling revealed the same genomic pattern found earlier in mouse models of pancreatic cancer. The scientists then devised a novel nanoparticle that selectively delivers genetic material to a tumor and prevents side effects in surrounding healthy tissues. To validate their findings, investigators injected the novel nanoparticles into pancreatic tumor-bearing mice and observed that by balancing these two targets they significantly prolonged the survival of the mice. "Taken together, our findings warrant this unique combined polyplex's potential as a novel nanotherapeutic for pancreatic ductal adenocarcinoma," study authors concluded.

 

LUNG CANCER

Stereotactic body radiation therapy versus surgery for early lung cancer among U.S. veterans

A recent study found that lobectomy prolonged survival compared with stereotactic body radiation therapy (SBRT) for patients with early-stage lung cancer (Ann Thorac Surg 2017; doi:10.1016/j.athoracsur.2017.07.048). The VA Informatics and Computing Infrastructure was utilized to identify patients diagnosed with biopsy-proven stage I NSCLC between 2006 and 2015. Survival was compared among those who underwent lobectomy, sublobar resection, or SBRT. The analysis included 4,069 patients; 73 percent (n=2,986) underwent lobectomy, 16 percent (n=634) underwent sublobar resection, and 11 percent (n=449) received SBRT. Investigators found that patients who received SBRT were older (mean age: 71 years vs. 66 years) and had more comorbidities (mean Charlson comorbidity index score, 1.59 vs. 1.33) than those who underwent surgery. At 30-day follow-up, mortality was 1.9 percent for lobectomy, 1.7 percent for sublobar resection, and 0.5 percent for SBRT due to operative risks, according to investigators. However, they observed that 5-year incidence of cancer death appeared lowest among those who underwent lobectomy (23%), followed by sublobar resection (32%) and SBRT (45%). "Among a large cohort of early-stage lung cancer patients, we found that lobectomy had improved survival compared with SBRT, although we found no survival difference between sublobar resection and SBRT," study authors concluded. "Despite these findings, the potential for unmeasured confounding remains and prospective randomized trials are needed to better compare these treatment modalities."

 

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