Evidence-Based Oncology July 2018
Evidence-Based Oncology July 2018
Surabhi Dangi-Garimella, PhD
Reporting by Surabhi Dangi-Garimella, PhD, and Jaime Rosenberg
Produced by Samantha DiGrande and Jaime Rosenberg
Reporting by Jaime Rosenberg, Mary Caffrey, Kelly Davio, and Christine Potkul
Reporting by Samantha DiGrande
Reporting by Samantha DiGrande
Link Found Between Mammographies, Other Screenings in Medicare EnrolleesWomen who undergo mammography screenings are more inclined to follow up with other preventive measures, according to new study results. US Medicare claims data gathered between 2010 and 2014 have found that women enrolled in Medicare were more likely to follow preventive guidelines and use those services following a mammography screening. The additional preventive screenings that were evaluated include bone mass measurement, Papanicolaou testing, and influenza vaccination.
For their study, published in Radiology,1 investigators at New York University (NYU) School of Medicine used a sample of women aged 65 years or older. The 555,705 women were sorted into 2 groups: 185,675 (33.4%) patients who received mammogram screenings and 370,080 (66.6%) who did not. The screened group was further divided between false and positive results and then subdivided among false-positive and true-positive patients.
The data were collected via multivariate logistic regression models and inverse probability of treatment weighting to evaluate the relationship between screening status and other preventive tests. Standards from the American College of Radiology were used to categorize results, because these factors play a critical role in the patient experience and willingness to participate in other preventive tests, according to the investigators.
The group of women who initially underwent mammography screenings, having either positive or negative results, had a greater chance of participating in a bone mass measurement (odds ratio [OR], 1.70; 95% CI, 1.63-1.78), Papanicolaou test (OR, 1.49; 95% CI, 1.40-1.58), and influenza vaccination (OR, 1.45; 95% CI, 1.37-1.53) compared with the control group. The study found that women with false-positive screenings showed no difference in their likelihood of undergoing further preventive testing. Also, at screening, false-positive and true-positive findings were found to be the same.
“Screening has the potential to identify early disease that can be curable,” said Stella Kang, MD, MSc, assistant professor in the departments of Radiology and Population Health at NYU School of Medicine, in a statement. “It’s encouraging to see that women undergoing mammography may have increased awareness to other preventive screening measures.”2 The current study sheds light on the idea of bundling preventive services for women.
The lack of data on the link between mammography screenings and other preventive tests motivated them to do this study, the investigators said. Further research must be done to reveal the association’s impact on policy and clinical practices.
- S Kang, M Jiang, R Duszak, Heller SL, Hughes DR, Moy L. Use of breast cancer screening and its association with later use of preventative services among Medicare beneficiaries [published online June 5, 2018]. Radiology. doi: 0.1148/radiol.2018172326.
- Study finds older patients who undergo mammography also are more likely to pursue other preven- tive tests [press release]. New York, NY: NYU Langone Health; June 4, 2018. newswise.com/articles/ view/695536/?sc=sphn. Accessed June 18, 2018.
MS Drug Could Reduce Adverse Events Associated With Cancer TreatmentFingolimod (Gilenya), an FDA-approved orally administered drug to treat multiple sclerosis, could reduce painful adverse effects (AEs) of multiple myeloma treatments, according to findings recently published in the Journal of Experimental Medicine.1
Chemotherapy-induced peripheral neuropathy (CIPN), a common and painful AE of many anticancer drugs, can persist for years, reducing quality of life for cancer survivors. Bortezomib (Velcade), which is used to treat multiple myeloma and mantle cell lymphoma, causes CIPN in over 40% of patients, but why this occurs was not previously known.
Investigators from Saint Louis University School of Medicine in Missouri have discovered that bortezomib causes the dysregulation of sphingolipid metabo- lism in the spinal cord and increases the levels of sphingosine 1-phosphate and dihydrosphingosine 1-phosphate. Higher levels of these molecules can activate S1PR1, a cell surface receptor protein, on specialized nervous system support cells called astrocytes. This results in neuroinflammation and enhanced release of the excitatory neurotransmitter glutamate.
In a preclinical model, rats treated with bortezomib had higher accumulations of sphingosine 1-phosphate and dihydrosphingosine 1-phosphate at the time they started to show signs of neuropathic pain. By blocking the production of these molecules with the fingolimod inhibitor, researchers prevented the animals from developing CIPN and even reversed its effects.
Notably, fingolimod did not inhibit bortezomib’s ability to kill myeloma cells. In fact, fingolimod was previously reported to inhibit tumor growth and enhance the effects of bortezomib in vitro and in tumor-bearing animals.2
“Our studies provide a compelling case for the consideration of repurposing [fingolimod] as an adjuvant to bortezomib for the prevention and treatment of chemotherapy-related neurotoxicity to address an immense unmet medical need,” concluded the study authors. “As [fingolimod] also shows promising anticancer potential and is FDA approved, rapid clinical translation of our findings is anticipated.”
- Stockstill K, Doyle T, Yan X, et al. Dysregulation of sphingolipid metabolism contributes to bortezomib-induced neuropathic pain. J Exp Med. 2018;215(5):1301-1313. doi: 10.1084/jem.20170584.
- Yasui H, Hideshima T, Raje N, et al. FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistance. Cancer Res. 2005;65(16):7478-7484. doi: 10.1158/0008-5472.CAN-05-0850.
New Immunotherapy Increases Survival Time for Patients With Brain CancerTocagen, a cancer-selective gene therapy company, is developing vocimagene amiretrorepvec (Toca 511) and extended-release 5-fluorocytosine (Toca FC), an immunotherapy for patients with recurrent brain cancer. Known as the Toca regimen, the investigational products are being evaluated in a phase 2/3 randomized, multicenter, open-label trial.1
The trial is being conducted at 68 sites across the United States, Canada, Israel, and South Korea in patients undergoing planned resection for recurrent glioblastoma or anaplastic astrocytoma. Enrollment is scheduled to be completed by the end of 2018.
After completion of the successful phase 1 study, the Toca regimen showed a favorable safety profile, extended patient survival compared with other therapies, and provided complete tumor shrinkage.2
In phase 2/3, patients will be randomized 1:1 to receive either the Toca regimen or standard of care treatment of single-agent chemotherapy (lomus- tine or temozolomide) or bevacizumab. The Toca regimen will involve 2 parts. In the first step, patients will receive Toca 511, a replicating virus that selec- tively infects cancer cells during surgery. The second step requires patients to receive cycles of Toca FC, a potent anticancer pill that kills cancerous cells and activates immune cells selectively to fight off cancerous ones, leaving healthy cells unharmed.3
“Toca 5 uses a virus to stimulate a patient’s own immune system and attack recurring high-grade gliomas—glioblastoma and anaplastic astrocytoma,” said Yaron Moshel, MD, PhD, a neurosurgeon with Atlantic NeuroSurgical Specialists and codirector of the Gerald J. Glasser Brain Tumor Center, the principal investigator for the local arm of the study in a statement.4
With the current standard of care treatment, newly diagnosed patients have a median survival 14 to 16 months. After recurrence, this falls to 7 to 9 months, on average.1 Conversely, phase 1 results of the Toca regimen showed a median longevity of 14.4 months for patients with a recurrence.
“Patients with complete tumor shrinkage are still alive almost 3 years after starting the Toca regimen. These results are encouraging—for patients, their loved ones, and the medical community—and we look forward to sharing further findings from phase 3 within the next 18 months,” Moshel said in statement.2
- Immunotherapy clinical trial reveals brain tumor shrinkage, continues with phase 3 study [press release]. Summit, NJ: Atlantic Health System; May 29, 2018. newswise.com/articles/view/695219/?sc=mwhr&xy=10022175. Accessed June 19, 2018.
- Walbert T, Bota D, Vogelbaum MA, et al. Intravenous delivery of Toca 511 in patients with high grade glioma results in quantifiable expression of cytosine deaminase in tumor tissue. Neuro-oncology. 2017;19(suppl 6):30- 31. doi:10.1093/neuonc/nox168.116.
- The Toca 5 Trial: Toca 511 & Toca FC versus standard of care in patients with recurrent high grade glioma (Toca5). clinicaltrials.gov/ct2/show/NCT02414165. Updated May 16, 2018. Accessed June 19, 2018.
- Immnunotherapy clinical trial reveals brain tumor shrinkage continues with phase 3 study [press release]. Summit, NJ: Atlantic NeuroSurgical Specialists; April 25, 2018. prnewswire.com/news-releases/immunotherapy-clinical-trial-reveals-brain-tumor-shrinkage-continues-with-phase-3-study-300635663.html. Accessed June 19, 2018.
Pembrolizumab Indications Expand to Include Cervical CancerThe indications of pembrolizumab (Keytruda) now include recurrent or metastatic cervical cancer with disease progression on or after chemotherapy for patients whose tumors express PD-L1, the FDA announced on June 12.1
The agency approved this expanded indication following a priority review based on tumor response rate and durability of response. Pembrolizumab’s indications include an earlier approval as a first-line treatment in patients with metastatic non–small cell lung cancer, as well as unresectable or metastatic melanoma.
“Keytruda is now the first anti-PD-1 therapy approved for the treatment of advanced cervical cancer, providing an important new second-line option for certain patients with this disease,” Roy Baynes, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, said in a prepared statement.1 “This approval also marks the first indication for Keytruda in a gynecologic cancer and reflects our ongoing commitment to bring forward innovative treatment options across a broad range of cancers, including cancers that disproportionately affect women.”
The approval was based on results from the KEYNOTE-158 trial, in which 98 patients with recurrent or metastatic cervical cancer were enrolled in a multicenter, nonrandomized, open-label, multicohort trial. Participants were treated with 200 mg of pembrolizumab delivered intravenously every 3 weeks until they showed either unsafe levels of toxicity or documented disease progression. Patients without disease progression could be treated for up to 24 months, and a tumor status assessment was completed every 9 weeks for the first 12 months and every 12 weeks thereafter.