publication date: Mar. 13, 2020
FDA encourages inclusion of older adult patients in cancer clinical trials
FDA issued a draft guidance document, “Inclusion of Older Adults in Cancer Clinical Trials Guidance for Industry,” to provide recommendations to sponsors and institutional review boards for the inclusion of older adult patients, ages 65 years and older, in the clinical trials of drugs for the treatment of cancer.
The draft guidance recommends enrolling older adults in early phase studies of cancer clinical trials, if appropriate, to obtain information to better inform later phase studies. It also includes additional recommendations intended to facilitate a better understanding of the benefit-risk profile of cancer drugs in older adult patients regarding trial design, recruitment strategies, information collection and developing and reporting more discrete age groups.
“Enrolling a broad representation of patients in clinical trials is an important tenet of clinical research as it facilitates a better understanding of the drug’s benefits and risks across the patient population likely to take the drug,” Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement. “However, because cancer incidence increases with age, and given the aging U.S. population, it’s particularly important now more than ever to ensure that older adults are also enrolling in cancer clinical trials.”
It is important to have older adult patients in clinical trials because differences may exist between younger and older patients in drug response and toxicity. Older adults often have other diseases or conditions and may be taking medications that could impact the efficacy of either the cancer drug or other drugs they are taking and may also impact the incidence and the severity of adverse events.
“Unfortunately, adults aged 65 years and older, and especially those over 75 years old, are currently underrepresented in cancer clinical trials despite accounting for a growing segment of the cancer patient population.
“This has been a persistent issue in oncology and the FDA is engaged with stakeholders to improve the representation of older adults in cancer clinical trials. That is why today, we are providing recommendations on increasing the enrollment of older adults in cancer clinical trials, when appropriate,” Pazdur said.
Furthermore, there may be important differences in efficacy in older adult patients compared to the younger or general population, and information describing such differences should be conveyed to patients and health care providers where appropriate.
Phase III GY004 for Cediranib and Lynparza doesn’t meet PFS endpoint in ovarian cancer indication
The phase III GY004 trial examining primarily the efficacy and safety of investigational medicine cediranib in combination with Lynparza versus platinum-based chemotherapy in patients with platinum-sensitive relapsed ovarian cancer failed to meet its primary endpoint of progression-free survival.
The trial was conducted by NRG Oncology. AstraZeneca and Merck sponsor the trial.
The trial did not meet the primary endpoint in the intent-to-treat population of a statistically significant improvement in progression-free survival with cediranib in combination with Lynparza vs. platinum-based chemotherapy.
Cediranib is an investigational oral vascular endothelial growth factor receptor inhibitor.
“Despite these disappointing results, we remain committed to expanding on the benefits already demonstrated with Lynparza for patients with advanced ovarian cancer,” Jose Baselga, executive vice president of oncology R&D, AstraZeneca, said in a statement.
The safety and tolerability profiles observed in GY004 were generally consistent with those known for each medicine.
Copper IUDs less likely to contribute to cervical cancer than hormonal IUDs
Patients who used copper intrauterine devices were found to have a lower risk of high-grade cervical neoplasms compared to users of the levonorgestrel-releasing intrauterine system, according to a Columbia study recently published in Obstetrics & Gynecology.
Studies from the 1980s suggested reduced risk of cervical cancer among women who used an intrauterine contraceptive, though those studies did not differentiate between the varying types of IUDs. Furthermore, much of the data from those studies was collected prior to the availability of most hormonal IUDs (LNG-IUS).
By standardizing four decades’ worth of data from the Columbia University Irving Medical Center database through the OMOP Common Data Model and using high-level analytics developed within the Observational Health Data Sciences and Informatics (OHDSI) collaboration, the research team ran a retrospective cohort analysis of more than 10,000 patients who received IUDs.
The diagnosis of high-grade cervical neoplasia was 0.7% in the Cu IUD cohort and 1.8% in the LNG-IUS cohort.
“Copper and hormonal IUDs may have different physiological effects on the female genitourinary system,” says Matthew Spotnitz, MD, MPH, a Postdoctoral Research Scientist within the Department of Biomedical Informatics and lead author of this study. “Consequently, the risk of cervical neoplasms may be different for copper and hormonal IUD users. Our findings may help patients and healthcare providers make informed decisions about whether the benefits of hormonal IUD use, compared to copper IUD use, are greater than the risks.”
Spotnitz noted that the research team hopes to lead a network study across other databases within the OHDSI network, which spans 19 countries, 133 unique databases converted to the OMOP CDM, and more than one billion patient records.
“The proportions of women who use copper and hormonal IUDs may vary among institutions,” Spotnitz says. “Overall, IUD use has become more popular over the past 20 years. Copper IUD use has remained constant whereas hormonal IUD use has increased. The rising popularity of hormonal IUDs may be related to the fact that they decrease the pain and bleeding of menses.”
The study notes that more than 100 million women use IUDs as contraception around the world, and these findings have implications for the larger population of current IUD users.
The full study is entitled “Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users.”
DBMI assistant professor Karthik Natarajan, PhD, DBMI adjunct professor Patrick Ryan, PhD, and Epidemiology, Population and Family Health professor Carolyn Westhoff, MD, collaborated on this study. Natarajan is also affiliated with the Columbia Data Science Institute.
OHDSI is an international, open-science collaborative that looks to improve health by empowering a community to collaboratively generate the evidence that promotes better health decisions and better care.