Ovarian Cancer in the World: Epidemiology and Risk Factors

This is an excellent intro article that looks at all the factors associated with ovarian cancer including the distribution, rate of occurrence, and risk factors. It was published in the International Journal of Women's Health in 2019. The authors are: Momenimovahed, Tzinobiak, Taheri and Salehiniya.

Aim: Ovarian cancer is one of the most common gynecologic cancers that has the highest mortality rate. Considering the fact that knowledge on the incidence, mortality of ovarian cancer, as well as its risk factors is necessary for planning and preventing complications, this study was conducted with the aim of examining the epidemiology and risk factors of ovarian cancer in the world.

Materials and methods: In order to access the articles, Medline, Web of Science Core Collection, and Scopus databases were searched from their start to the year 2018. Full-text, English observational studies that referred to various aspects of ovarian cancer were included in the study.

Results: In total, 125 articles that had been published during the years 1925–2018 were entered into the study. Ovarian cancer is the seventh most common cancer among women. Increased risk factors of cancer have led to an upward trend in the incidence of cancer around the world. In 2018, 4.4% of entire cancer-related mortality among women was attributed to ovarian cancer. Although the incidence of cancer is higher among high Human Development Index (HDI) countries, the trend of mortality rate tends to be reversing. Various factors affect the occurrence of ovarian cancer, from which genetic factor are among the most important ones. Pregnancy, lactation, and oral contraceptive pills play a role in reducing the risk of this disease.

Conclusion: This study provides significant evidence about ovarian cancer. Considering the heavy burden of ovarian cancer on women's health, preventive measures as well as health education and early detection in high risk groups of women are highly recommended. Although some risk factors cannot be changed, a focus on preventable risk factors may reduce the risk of ovarian cancer. More studies are needed to explore the role of unclear risk factors in ovarian cancer occurrence.

Keywords: Ovarian cancer, epidemiology, risk factor

MEK Inhibition on Low Grade Serous OC

This short video from Memorial Sloan Kettering, Dr. Grisham discusses the role of MEK inhibitors. MEK is an enzyme that is involved in cell proliferation and cell death. 

What Triggers Dormant Cancer Cells?

This article first appeared in  StatNews. The Q&A section defines some of the terms used and what some unexpected findings were.

By Shraddha Chakradhar

The recurrence of cancer months or even years after successful treatment is an all too common phenomenon, and scientists have been chipping away at understanding how undetectable cells can once again unleash disease on the body — often more aggressively than the first time around.

In a new study published Wednesday in Science Translational Medicine, one group of researchers describes how a cascade of events set off by high levels of a stress hormone could cause dormant tumor cells to reawaken to once again cause cancer.

The hormone, norepinephrine, is naturally found in the body, but more of this chemical is released into the bloodstream when the body detects higher levels of stress. In some cancer models, scientists found that an elevated level of norepinephrine led to the activation of cells known as neutrophils, which help shield tumor cells from the body’s immune system. Activating neutrophils in turn led to these cells releasing a special type of lipid — which then awakened sleeping cancer cells.

NCCN Guidelines on Treatment of OC

 

This is a great panel discussion about the current treatment guidelines for treating OC that was updated in 2020.

This article first appeared in AJMC and is reprinted here.

One patient had a complete response and the majority of patients achieved disease control at 12 weeks.

A phase 1 trial of an anti-folate receptor alpha (FolRα) human immunoglobulin G1 (IgG1) antibody for women with advanced ovarian cancer showed responses in 32% of evaluable patients, including 1 complete response (CR).

The results were announced by Sutro Biopharma, which is developing its candidate STRO-002; the FolRα targeting antibody-drug conjugate (ADC) uses non-natural amino acids to target FolRα, which is overexpressed in some cancers, including ovarian cancer.

The ongoing dose-escalation phase 1 study, STRO-002-GM1, is a single-arm monotherapy trial for patients with ovarian cancer not selected based on their FolRα-expression levels. The dose-escalation portion of the study was fully enrolled with 39 patients in August 2020. Patients were heavily pre-treated and had a median of 6 prior lines of therapy, platinum-based regimens, bevacizumab, poly-ADP-ribose polymerase inhibitors, and checkpoint inhibitors.

Results included those from 34 patients treated with clinically active dose levels, 2.9 mg/kg or higher, of which 31 patients had post-baseline scans and were evaluable for RECIST responses. At the data cutoff of October 30, 2020, median time on treatment was 19 weeks and 10 patients remained on treatment. Results out of 31 evaluable patients included:

• 10 patients met RECIST criteria for response, with 1 achieving a CR and 9 patients achieving a partial response (PR)
• Of the PRs, 3 were confirmed PRs and 6 unconfirmed PRs
• 23 patients (74%) achieved disease control at 12 weeks
• 18 patients (58%) achieved disease control at 16 weeks
• 4 patients (13%) were on treatment for 52 weeks
• 3 patients remained on treatment beyond 64 weeks

The drug was well-tolerated; 86% of all treatment-emergent adverse events (AEs) were grade 1 or 2. The most common grade 3 and 4 AEs were reversible neutropenia. Grade 3 arthralgia (15.4%) and neuropathy (7.7%) were observed and managed with standard medical treatment.

“We are encouraged to see meaningful clinical benefit from STRO-002 for patients with advanced platinum-resistant and refractory ovarian cancer. The women on the study are heavily pretreated and have limited treatment options as many have received experimental agents and participated in other clinical trials,” said Lainie P. Martin, MD, who heads the Gynecology/Oncology Program at Hospital of the University of Pennsylvania and an investigator on the STRO-002 study. “The deepening of responses in patients as well as disease control over time demonstrates STRO-002 to be an important potential treatment option for patients with ovarian cancer.”

The company said that although a maximum tolerated dose was not reached, it plans to randomize dose levels of 4.3 and 5.2 mg/kg in the dose-expansion trial with less heavily pre-treated patients. The candidate is also being studied in endometrial cancer.

This article was published by AJMC.

 

PARPi Appear Linked to Blood Cancers

 This article first appeared on Medpage Today.

By: Leah Lawrence

Although rare, poly-ADP ribose polymerase (PARP) inhibitors were associated with an increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and occurred even after brief drug exposure, researchers reported.

A systematic review and meta-analysis of 18 randomized clinical trials comparing PARP inhibitors to placebo control in adults revealed more than double the risk for MDS and AML (Peto odds ratio [OR] 2.63, 95% CI 1.13-6.14, P=0.026) with PARP inhibitors, reported Joachim Alexandre, MD, of Caen University Hospital, France, and colleagues.

All cases were reported in ovarian cancer trials. Writing in the Lancet Haematology, the researchers said this could be explained by these trials having the longest follow-up compared with other tumor types.

Incidence of MDS and AML across PARP inhibitor groups was 0.73% compared with 0.47% for placebo groups. When studies that included other control treatments were included in the analysis, PARP inhibitor treatment still significantly increased the risk for MDS and AML (Peto OR 2.25, 95% CI 1.07-4.75, P=0.033).

An additional analysis of real-world data from VigiBase focused on clinical features on 99 cases of MDS and 79 cases of AML related to PARP inhibitor treatment. Among these cases, the median duration of PARP inhibitor exposure was 9.8 months, but ranged from 0.2 to 66.8 months. The median latency period for MDS and AML from first PARP inhibitor exposure was 17.8 months, ranging from 0.6 months to 66.8 months. Specifically, MDS occurred after a median of 17.8 months from first exposure; AML, 20.6 months.

“These delays to onset of myelodysplastic syndrome and acute myeloid leukemia are shorter than typically described with conventional chemotherapeutic drugs,” the researchers noted.

Outcomes were available for 104 cases of MDS/AML: 9% reported recovery, 46% of cases were ongoing, and 45% of cases resulted in death.

Alexandre and colleagues noted that the significant risk for MDS and AML related to PARP inhibitor treatment in first-line maintenance trials “suggest that these events might be a toxicity specific to PARP inhibitors.” However, in the SOLO2 trial of women with platinum-sensitive, relapsed, BRCA1/2-mutated ovarian cancer, PARP inhibition was associated with improved median overall survival; long-term follow-up showed 16 cases of MDS or AML in the PARP inhibitor group and four cases in the placebo group.

“We cannot exclude a competitive bias between death and myelodysplastic syndrome or acute myeloid leukemia occurrence, and therefore we cannot exclude that these adverse events could have a stronger association with previous lines of chemotherapy than with PARP inhibition,” Alexandre and colleagues wrote.

In an editorial that accompanied the study, Anna Tinker, MD, of the University of British Columbia in Vancouver, Canada, noted that maturing data from randomized clinical trials of PARP inhibitors in a growing number of tumor types might further refine the low overall incidence of MDS and AML found in this study and could reveal if “risk might differ in a drug-specific manner.”

Subgroup analyses by Alexandre and colleagues showed no significant differences in risk for MDS or AML by previous systemic therapy, PARP inhibitor used, biomarker specificity, PARP inhibitor treatment setting, PARP inhibition assignation, follow-up duration, or PARP inhibitor treatment duration.

“Given the common use of PARP inhibitors in BRCA1/2 mutation carriers, the finding that these patients do not appear to have elevated risk is reassuring,” Tinker wrote. “Commonly labeled as a late toxicity, clinicians need to remain aware that the onset of myelodysplastic syndrome and acute myeloid leukemia can occur soon after PARP inhibitor initiation even after brief drug exposure.”

Patients should be counseled “on the rare but life-threatening toxicities of PARP inhibitors,” she wrote, and offered “appropriate monitoring and investigations of hematological changes.”

This article was published by Medpage Today.