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.
BLOOD CANCERS
Function, survival, and care utilization among older adults with hematologic malignancies
Although the majority of patients who have blood cancers are older adults, they make up only a small percentage of participants in the clinical trials that lead to new therapies. Recently, a team of researchers examined older adults who have cancer to see whether their ability to manage daily activities as measured by these assessments was linked to staying alive longer (J Am Geriatr Soc 2019; doi:10.1111/jgs.15835). A key part of the geriatric assessment is to determine how well an older adult performs the basic activities of daily living (ADLs). The geriatric assessment also takes into account an older adult's ability to perform instrumental activities of daily living (IADLS), or activities necessary for them to live on their own in the community. The researchers studied how performing daily activities was linked to survival and also to the use of medical care for adults living with cancer and aged 75 years and older. Participants included 464 people who on average were nearly 80 years old; 65 percent were male. All the participants were treated for blood cancers, including leukemia, multiple myeloma, and lymphoma.
Of the participants, 11 percent reported they had trouble with at least one ADL and almost 27 percent had trouble performing at least one IADL. The researchers also looked at a group of 318 participants who had visited the ED or had unplanned hospitalizations. Of them, 17 percent had at least one ED visit and 19 percent had at least one unplanned hospitalization. The five most common causes of hospitalization were pneumonia, fever, sepsis, pain, and congestive heart failure. The researchers reported that participants who had trouble performing at least one IADL had a higher risk for death, ED visits, and unplanned hospitalizations. This risk was not affected by how old they were, whether they had other chronic illnesses, how aggressive their cancers were, or the intensity of their cancer treatment.
CERVICAL CANCER
The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up
A potential new immune-based therapy to treat precancers in the cervix completely eliminated both the lesion and the underlying HPV infection in a third of women enrolled in a clinical trial (Gynecol Oncol 2019; doi:10.1016/j.ygyno.2019.03.250). The shot, a therapeutic vaccine, injects a specific protein that triggers an immune system response to attack high-risk HPV types that cause nearly all cervical intraepithelial neoplasia (CIN). The study enrolled 192 women diagnosed with CIN2 or CIN3, randomizing 129 to receive the vaccine and 63 to receive a placebo. Women were given three shots in their thigh, one per week for 3 weeks. Six months later, the women were treated with standard surgical procedures for CIN 2/3 and the removed tissue was examined. Women who received the vaccine were more than twice as likely as those who received placebo to see their CIN eliminated regardless of the type of HPV infection. The results were most striking in the more-severe CIN3: at least 15 percent and as much as 36 percent of those who got the vaccine saw their CIN3 eliminated, while none of the women in the placebo group did. Participants were followed for another 2.5 years after surgery. They showed that long-term follow-up was better for those who received vaccine over placebo, with more women in the vaccine group remaining completely clear of HPV.
SKIN CANCER
Topical kinase inhibitors induce regression of cutaneous squamous cell carcinoma
Treating precancerous skin lesions with topical targeted therapies may significantly reduce their size and inhibit the growth of cutaneous squamous cell carcinoma (Exp Dermatol 2019; doi:10.1111/exd.13902). The team tested the efficacy of dasatinib, BEZ-235, and 5-fluorouracil using a transgenic mouse model in two separate experiments. In this model, the skin cancer shows activation of Src-family tyrosine kinases and downstream signaling pathways, including PI3K/mTOR, Ras/MAPK, and JAK/STAT. Researchers measured the size of the lesions and took biopsies of treated mice and controls to assess tumor regression, inflammation, and epidermal ulcers at designated time points over a 5-week time period. Overall, topical dasatinib induced regression of the cancer similar to topical 5-fluorouracil but with less inflammation and no ulcers. Dasatinib applied daily to mice induced 45 percent and 77 percent regression of cutaneous squamous cell carcinoma after 2 and 5 weeks of treatment, respectively, compared to controls. 5-fluorouracil induced 70 percent regression at 2 weeks in eight mice; however, it was associated with epidermal ulcers in two out of 15 of the tumors observed, and seven of the eight mice in that group died. No ulcers or deaths were observed in the dasatinib or control groups. In a second experiment, the researchers found that BEZ-235 acted similarly to dasatinib. The treatment induced regression of the cancer by over 60 percent compared to control lesions at 5 weeks without significant inflammation or ulcers "These data indicate that topical small molecule kinase inhibitors targeting drivers of AK/SCCIS/cSCC growth represent a promising therapeutic approach to treat these common skin lesions," study authors wrote.
OVARIAN CANCER
Olaparib and [alpha]-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial
About a third of patients with ovarian cancer who wouldn't be expected to respond to PARP inhibitors had partial shrinkage of their tumors when a second, targeted drug was added to treatment, according to recent data (Lancet Oncol 2019; https://doi.org/10.1016/S1470-2045(18)30905-7).
The phase I trial, which combined the PARP inhibitor olaparib with alpelisib, an investigational drug that targets the cell protein PI3-Kinase alpha, included 28 patients with high-grade serous ovarian cancer received the drug combination. Of these patients, ten (36%) achieved a partial response and 14 (50%) had stable disease according to Response Evaluation Criteria in Solid Tumors 1.1. Maximum tolerated dose and recommended phase II dose were identified as alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3), according to researchers. The most common treatment-related grade 3-4 adverse events, considering all dose levels, were hyperglycaemia, nausea, and increased alanine aminotransferase concentrations. No treatment-related deaths occurred. Dose-limiting toxic effects included hyperglycaemia and fever with decreased neutrophil count. "Combining alpelisib and olaparib is feasible with no unexpected toxic effects," study investigators concluded. "The observed activity provides preliminary clinical evidence of synergism between olaparib and alpelisib, particularly in epithelial ovarian cancer, and warrants further investigation."
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