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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 is here to help with summaries of the newest studies to ensure you are up-to-date on the latest innovations in oncology practice.



Randomized, double-blind, phase II study of temozolomide in combination with either veliparib or placebo in patients with relapsed-sensitive or refractory small-cell lung cancer

A randomized, phase II trial showed that adding the PARP inhibitor veliparib to a standard chemotherapy agent improved overall response rates (ORR) in patients with small cell lung cancer (SCLC) (J Clin Oncol 2018; doi:10.1200/JCO.2018.77.7672). Additionally, researchers identified a select group of patients-those whose tumors expressed SLFN11-who also saw a progression-free survival (PFS) and overall survival (OS) benefit. Investigators enrolled 104 patients with relapsed SCLC from seven centers across the country. Between 2012 and 2015, patients were randomized to receive either veliparib or placebo twice daily, with a standard chemotherapy regimen temozolomide (TMZ). The primary endpoint was PFS at 4 months; secondary endpoints included, ORR, OS, and safety and tolerability of veliparib with TMZ. Response was determined by imaging at weeks 4 and 8, followed by every 8 weeks thereafter. Toxicities associated with the PARP therapy include blood count deficiencies, but treatment generally was well-tolerated, according to researchers. At 4 months, data showed, in an unselected population, the study did not reach a statistically significant difference in PFS between the TMZ/veliparib cohort (36%), and TMZ/placebo cohort (27%). In the two groups, the median OS also was similar at 8.2 months and 7 months, respectively. Researchers found that the ORR was almost three times higher in the TMZ/veliparib cohort compared to the TMZ/placebo cohort (39% vs. 14%). Additionally, among patients whose tumors expressed the elevated levels of SLFN11, treatment with TMZ/veliparib resulted in significantly prolonged PFS (5.7 vs. 3.6 months) and OS (12.2 vs. 7.5 months), according to investigators.



Age correlates with response to anti-PD1, reflecting age-related differences in intratumoral effector and regulatory T-cell populations

With each decade of life, the likelihood of progression of melanoma after treatment with anti-PD1 immunotherapy decreased by 13 percent, according to a new study (Clin Can Res 2018; doi:10.1158/1078-0432.CCR-18-1116). Researchers analyzed data from 538 patients with melanoma treated with the anti-PD1 therapy pembrolizumab at eight different institutes worldwide. Of the patients, 238 were younger than 62 years. Investigators found that 50 percent of patients younger than 62 years, compared with only 37 percent of patients 62 years or older, had poor response to the treatment. This finding was independent of gender or prior treatment with MAPK inhibitor (MAPKi) therapies, study authors reported. Further experiments were conducted using mice to understand the relationship between the aging microenvironment and response to anti-PD1 immunotherapy. Results showed that young mice were more resistant to anti-PD1 therapies than aged mice. Further research revealed differences in the immune microenvironment of the two groups of mice. A subpopulation of T cells that are known to be immunosupressive, FOXP3-positive Tregs, were fewer in older mice compared with younger mice. Primary and metastatic melanoma samples were analyzed from another cohort of 268 patients for the presence of the protein FOXP3 in T cells and researchers found that the FOXP3-positivity of intratumoral T cells decreased in patients over 50 years of age. The researchers also observed age-related differences in the T-cell subpopulations within the tumors of these patients. "While there are obvious limitations to our study, including our inability to conduct a meta-analysis due to a lack of available data, and our inability to control for mutational burden, there is a remarkable consistency in these data from over 500 patients across eight different institutes worldwide," according to study authors. "These results stress the importance of considering age as a factor for immunotherapy response."



Long-term psychological and educational outcomes for survivors of neuroblastoma: a report from the Childhood Cancer Survivor Study

A new study revealed that pediatric neuroblastoma patients are at elevated risk for long-term psychological impairment (Cancer 2018; doi:10.1002/cncr.31379). To assess the long-term psychological effects of neuroblastoma and its treatment, researchers studied 859 children who had been diagnosed with neuroblastoma at least 5 years earlier and were under 18 years old. Their median age at diagnosis was 0.8 years, and they were followed for a median of 13.3 years. These 859 neuroblastoma survivors were compared with 872 siblings of childhood cancer survivors. Compared with siblings, neuroblastoma survivors had an increased prevalence of impairment in the domains of anxiety/depression (19% vs. 14%), headstrong behavior (19% vs. 13%), attention deficits (21% vs. 13%), peer conflict/social withdrawal (26% vs. 17%), and antisocial behavior (16% vs. 12%). Common treatments-vincristine, cisplatin, and retinoic acid-were not associated with impairment, but survivors who developed chronic health conditions as a result of their cancer treatment were at higher risk for developing worse outcomes, researchers reported. "Neuroblastoma survivors are at elevated risk for psychological impairment, which is associated with special education service usage and lower adult educational attainment," study authors noted. "Those with chronic health conditions may represent a high-risk group for targeted screening and intervention."



Parents' views on the best and worst reasons for guideline-consistent HPV vaccination

Parents of adolescents believed that the potential to prevent certain types of cancer is the best reason for their children to receive the HPV vaccine, whereas other reasons health care providers often give were far less persuasive, according to recently published data (Cancer Epidemiol Biomarkers Prev 2018; doi:10.1158/1055-9965.EPI-17-1067). Researchers developed a best-worst scaling experiment to evaluate 11 reasons health care providers typically give for HPV vaccination. The experiment was administered in 2016 via a national online survey of 1,177 parents of adolescents ages 11-17, according to study authors. Fifty-seven percent of the parents had initiated HPV vaccination. Parents said "it can prevent some types of cancer" was the best reason to get the HPV vaccination. Parents also felt that "it can prevent a common infection;" "it has lasting benefits;" and "it is a safe vaccine" were persuasive reasons, researchers reported. According to survey results, parents said the worst reasons providers could give included "it is a scientific breakthrough;" "I got it for my own child;" and "your child is due for it." Stratified analyses were utilized to evaluate whether the parents' opinions would vary depending on their overall confidence in vaccines. Researchers found that vaccine confidence did not appear to significantly affect parents' perceptions of physicians' messages, and cancer prevention was the most effective message for both groups. "Parents prioritized cancer prevention as the best reason for guideline-consistent HPV vaccination. Several other common reasons, including having vaccinated one's own child, may warrant additional testing," study authors concluded. "Providers should emphasize cancer prevention when discussing HPV vaccination, as recommended by the CDC, the President's Cancer Panel, and others."


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