Vincristine, Racial Disparities in Multiple Myeloma, and HER2 Metastatic Breast Cancer Are in the News
Yvette Florio Lane
Breast Cancer, FDA Approvals, News & Updates, In the News, Multiple Myeloma, Pediatric Cancer
Critical Shortage of Pediatric Cancer Drug Leads to Serious Concerns
Study Finds Racial Disparities in Multiple Myeloma Treatment
FDA Grants Priority Review to Trastuzumab Deruxtecan for HER2-Positive Metastatic Breast Cancer
The past week in oncology-related news includes shortages of crucial pediatric cancer drug, results of a study of racial disparities in multiple myeloma, and new drug on the horizon for HER2 metastatic breast cancer.
On October 16, 2019, the FDA announced that there was a critical shortage of vincristine,1 a drug that has served as the backbone of treatment regimens for pediatric cancers for several decades.2 Vincristine is critically important for the treatment of a variety of malignancies, and is included on the World Health Organization's lists of essential medicines3 and essential medicines for children.4
Although a shipment of the drug is in transit, and the crisis is predicted to ease by late October, actual shortages will not likely be resolved until December at the earliest.1 The Drug Shortages Staff of the FDA considers a shortage "resolved" when the market is "covered," that is, when supply is available to cover total market demand.5
The shortage of vincristine is likely to affect children across the country whose cancer treatment relies on the drug. Earlier this week, in a news report on the shortage, the New York Times quoted pediatric oncologists who may begin rationing the drug to their patients or employing other measures to conserve quantities of the medication.6 This prospect caused alarm among many physicians and patient representative groups who quickly responded with petitions and calls to the government to intervene with measures to ameliorate the current shortage and to prevent such events in the future.7
The possibility of the shortage has been on the horizon since July, when Teva Pharmaceuticals, 1 of only 2 manufacturers of the drug, alerted the FDA that they would cease production of vincristine "for business reasons."8 Only 1 other US pharmaceutical manufacturer, Pfizer, produces the drug.
Pfizer spokesperson Jessica Smith said that the company was attempting to produce as much as 4 times its usual output of vincristine in response to the expected shortage.6 However, the company experienced delays and has been unable to meet production goals. Pfizer posted a letter to customers on the FDA's website on October 18, in which they stated the drug was being expedited and the company expected a full recovery of supplies by January 2020.9
Generic drugs are widely used in cancer treatment. Some drugs, such as vincristine, which has been off-patent for decades, are difficult to produce and have a narrow profit margin, making them unattractive to manufacturers. Former FDA Commissioner Scott Gottlieb formed a panel in 2018 to explore shortages and remedy the problem.10
Current and Resolved Drug Shortages and Discontinuations Reported to FDA. www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Vincristine%20Sulfate%20Injection,%20USP%20(Preservative-Free)&st=c&tab=tabs-1.
Foster V. The U.S. is running out of a critical childhood cancer drug and there is no suitable replacement. Forbes. October 15, 2019. www.forbes.com/sites/victoriaforster/2019/10/15/the-us-is-running-out-of-a-critical-childhood-cancer-drug-and-there-is-no-suitable-replacement/#30c864873c97.
World Health Organization Model List of Essential Medicines, 21st List, 2019. Geneva: World Health Organization; 2019. License: CC BY-NC-SA 3.0 IGO. https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf?sequence=1&isAllowed=y.
World Health Organization Model List of Essential Medicines for Children, 7th List, 2019. Geneva: World Health Organization; 2019. License: CC BY-NC-SA 3.0 IGO. https://apps.who.int/iris/bitstream/handle/10665/325772/WHO-MVP-EMP-IAU-2019.07-eng.pdf?ua=1.
Current and Resolved Drug Shortages and Discontinuations Reported to FDA. www.accessdata.fda.gov/scripts/drugshortages/default.cfm?utm_campaign=10-17-2019%20Drug%20Shortages&utm_medium=email&utm_source=Eloqua&elqTrackId=e788f63a324b432696cc8324ef291730&elq=17506ca6126547f3bc4d2c7691f325ea&elqaid=9912&elqat=1&elqCampaignId=8277.
Rabin RC. Faced with a drug shortfall, doctors scramble to treat children with cancer. New York Times. October 14, 2019. www.nytimes.com/2019/10/14/health/cancer-drug-shortage.html?smtyp=cur&smid=fb-nytimes.
Children's Oncology Group. www.childrensoncologygroup.org/downloads/Vincristine_Shortage. A_Letter_to_the_Community. Oct_2019.pdf.
Current and Resolved Drug Shortages and Discontinuations Reported to FDA. www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Vincristine+Sulfate+%28VINCASAR+PFS%29+Injection%2C+USP&st=d&tab=tabs-2.
Pfizer. Supply Update Notification for Vincristine Sulfate Injection, USP Presentations. October 18, 2019. Dear Customer. www.fda.gov/media/131865/download.
Statement from FDA Commissioner Scott Gottlieb, M.D., on FDA's work to mitigate shortages of intravenous drugs, shorten supply disruptions and better predict vulnerabilities. May 31, 2018. www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-fdas-work-mitigate-shortages-intravenous-drugs-shorten.
A study published this week in Blood Advances, the peer-reviewed journal of the American Society of Hematology, found racial disparities in treatment patterns and outcomes among patients with multiple myeloma (multiple myeloma).1
The retrospective study used updated real-world patient data from the Surveillance Epidemiology and End Results (SEER)-Medicare database from 2007 to 2013. It included 3504 white, 858 African Americans, and 468 Hispanic patients with a confirmed multiple myeloma diagnosis who were continuously enrolled in Medicare parts A, B, and D from 6 months before their initial diagnosis date, to at least 6 months after their initial diagnosis date, or death, whichever occurred first.2 Patients whose racial/ethnic identification fell outside of these 3 categories were not included. The SEER-Medicare database did not contain a clinical measure of disease severity or stage.
Although overall survival (OS) was similar among the racial/ethnic cohorts, researchers found several differences suggesting that African Americans and Hispanics may not be fully benefiting from novel therapies, including the immunomodulatory drugs lenalidomide and pomalidomide, and the proteasome inhibitors bortezomib and carfilzomib, because they receive them later than whites. Earlier introduction and the increased use of novel therapies such as these have nearly doubled the OS of patients with multiple myeloma within the past decade.2
Researchers found that the use of novel therapies increased among all 3 cohorts, but compared with white patients, African Americans and Hispanics received novel therapies later after multiple myeloma diagnosis; and although the use of novel therapies increased over time among all 3 cohorts, this increase was more pronounced among white patients compared with African American patients.
They also found that the rate of autologous stem-cell transplantation (ASCT) within 1 year of multiple myeloma diagnosis increased for white and African American patients, but not for Hispanic patients, who had the lowest rates of ASCT overall. For transplant-eligible patients, ASCT remains the standard of care, providing a greater benefit when used earlier in the treatment paradigm of multiple myeloma.2
One positive finding, the increasing trend toward starting therapy within the first 6 months of diagnosis among the 3 race/ethnicity cohorts, was offset by the fact that this trend was more pronounced among white and Hispanic patients than African Americans.2
Multiple myeloma accounts for approximately 10% of hematologic malignancies. In 2018, there was approximately 30,770 new cases of multiple myeloma and approximately 12,770 deaths attributable to the disease in the United States. Multiple myeloma is relatively rare but occurs more frequently in men and among African Americans. As of 2015, approximately 125,000 Americans were living with the disease.2
American Society of Hematology. Study finds racial disparities in the treatment of multiple myeloma patients. Press release. October 17, 2019. www.hematology.org/Newsroom/Press-Releases/2019/9972.aspx. Accessed October 18, 2019.
Ailawadhi S, Parikh K, Abouzaid S, et al. Racial disparities in treatment patterns and outcomes among patients with multiple myeloma: a SEER-Medicare analysis. Blood Adv. 2019;3:2986-2994.
On October 17, 2019, the FDA accepted the Biologics License Application (BLA) for priority review for trastuzumab deruxtecan (DS-8201) for the treatment of patients with HER2-positive metastatic breast cancer (metastatic breast cancer), according to a press release from AstraZeneca.1 If approved, trastuzumab deruxtecan would expand the treatment options for patients with HER2-positive metastatic breast cancer, which remains incurable. Approximately 1 in 5 breast cancers are HER2-positive.
Trastuzumab deruxtecan is an antibody-drug conjugate that targets the tyrosine kinase receptor HER2 found on the surface of some cancer cells. The presence of the growth-promoting protein is associated with aggressive disease and a poorer prognosis.2
The BLA was based on combined results from a phase 1 clinical trial,3 which showed an overall response rate of 59.5% (95% confidence interval [CI], 49.7-68.7) and a disease control rate of 93.7% (95% CI, 87.4-97.4) with trastuzumab deruxtecan, and the pivotal, open-label, global multicenter, phase 2 DESTINY-Breast01 clinical trial, in which researchers evaluated the efficacy and safety of trastuzumab deruxtecan in 253 patients with HER-positive, unresectable and/or metastatic breast cancer who were previously treated with trastuzumab emtansine.1
Additional results from the DESTINY-Breast01 trial will be reported in December at the 2019 San Antonio Breast Cancer Symposium.
Trastuzumab deruxtecan was previously granted FDA Breakthrough Therapy designation and Fast Track designation. The Prescription Drug User Fee Act date for [fam-] trastuzumab deruxtecan is set for the second quarter of 2020.
AstraZeneca. Trastuzumab deruxtecan granted FDA priority review for treatment of patients with HER2-positive metastatic breast cancer. Press release. October 17, 2019. www.astrazeneca.com/media-centre/press-releases/2019/trastuzumab-deruxtecan-granted-fda-priority-review-for-treatment-of-patients-with-her2-positive-metastatic-breast-cancer-17102019.html. Accessed October 18, 2019.
American Cancer Society. Breast cancer HER2 status. September 20, 2019. www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed October 18, 2019.
Tamura K, Tsurutani J, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20:816-826.
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