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The following information helps you to find FDA Alerts and Pharmacist’s Applications to Practice quickly and easily. In cooperation with the Food and Drug Administration (FDA), and as a service to our members, HOPA periodically distributes information about newly approved therapies for cancer patients from FDA’s Office of Oncology Drug Products Director, Dr. Richard Pazdur to inform oncologists and professionals in oncology-related fields in a timely manner. Links to product labels will take you to relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, HOPA does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.

Along with HOPA’s Publications Committee, members also review new drug updates and provide analysis and research on the application of these new drugs or indications. Pharmacist’s Applications to Practice, or PAP, are listed after drugs that include the additional analysis. If you are interested in helping the Publications Committee with creating a Pharmacist's Application to Practice, please contact Jeff Price at jprice@hoparx.org.

You can also find additional information on FDA Alerts and Updates by listening to FDA Drug Safety Podcasts.


September 14, 2017

http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761028s000lbl.pdf

On September 14, 2017, the U.S. Food and Drug Administration approved Mvasi (bevacizumab-awwb, Amgen Inc.) as a biosimilar to Avastin (bevacizumab, Genentech Inc.). Mvasi is the first biosimilar approved in the U.S. for the treatment of cancer.

Mvasi is approved for the treatment of patients with the following cancers:

  • Metastatic colorectal cancer, in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment. Mvasi is not indicated for the adjuvant treatment of surgically resected colorectal cancer.
  • Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrmidine-oxaliplatin-based chemotherapy for the second-line treatment of patients who have progressed on a first-line bevacizumab product-containing regimen.
  • Non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease.
  • Glioblastoma with progressive disease following prior therapy, based on improvement in objective response rate. No data available demonstrating improvement in disease-related symptoms or survival with bevacizumab products.
  • Metastatic renal cell carcinoma, in combination with interferon alfa.
  • Cervical cancer that is persistent, recurrent, or metastatic disease, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.

Health care professionals should review the prescribing information in the labeling for detailed information about the approved uses:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761028s000lbl.pdf

The approval was based on comparisons of extensive structural and functional product characterization, animal data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity between Mvasi and U.S.-licensed Avastin demonstrating that Mvasi is highly similar to US-licensed Avastin and that there are no clinically meaningful differences between the products. It has not been shown to be interchangeable with U.S.-licensed Avastin.

Common expected side effects of Mvasi include epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, and exfoliative dermatitis. Serious expected side effects of Mvasi include perforation or fistula, arterial and venous thromboembolic events, hypertension, posterior reversible encephalopathy syndrome, proteinuria, infusion-related reactions, and ovarian failure

Like Avastin, the labeling for Mvasi contains a Boxed Warning to alert health care professionals and patients about an increased risk of gastrointestinal perforations, surgery and wound healing complications, and severe or fatal hemorrhage.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


Pharmacist’s Applications to Practice

Bevacizumab-awwb (Mvasi) for Certain Brain, Cervical, Colorectal, Kidney, and Lung Cancers

Authors: Marcus Tad Autry, PharmD
PGY-2 Ambulatory Care Resident
University of Oklahoma College of Pharmacy
Oklahoma City, OK

Sarah Schmidt, PharmD BCOP BCPS
Oncology Clinical Specialist—Bone Marrow Transplant and Hematology
Stephenson Cancer Center
Oklahoma City, OK

What is the potential role for bevacizumab-awwb (Mvasi) in the management of selected solid tumor cancers?

  • Bevacizumab-awwb (Mvasi) is the second biosimilar to a biologic medication that has been approved by the U.S. Food and Drug Administration (FDA).
  • It is a biosimilar to bevacizumab (Avastin).
  • It is a vascular endothelial growth factor (VEGF) inhibitor. Inhibition of VEGF binding to the receptors FLT-1 and KDR on endothelial cell membranes inhibits angiogenesis, thereby inhibiting microvascular growth. Inhibition of microvascular growth is believed to inhibit growth of tissues, including cancer tissue.1
  • As a biosimilar to Avastin, Mvasi has the same FDA approval for treatment of the following malignancies:
    • first- or second-line treatment of metastatic colorectal cancer (mCRC) with intravenous (IV) 5-fluorouracil-based regimen
    • second-line treatment of mCRC in combination with a fluoropyrimidine with oxaliplatin or irinotecan after disease progression on a first-line regimen containing a bevacizumab product\
    • first-line treatment for unresectable, locally advanced, recurrent, or metastatic nonsquamous non-small-cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel
    • single-agent therapy for progressive glioblastoma following prior therapy
    • metastatic renal cell carcinoma (RCC) in combination with interferon alfa
    • persistent, recurrent, or metastatic cervical cancer in combination with paclitaxel with cisplatin or topotecan.2-4
  • Approval for Mvasi for the above cancers uses the pathway for biosimilars under 351(k) of the Public Health Service Act. At least one clinical study comparing the biosimilar to the reference drug must occur for approval. In the case of bevacizumab-awwb, NSCLC was assessed.5,6
  • In this phase 3 double-blind active-control trial, Mvasi in combination with carboplatin and paclitaxel was compared to Avastin in combination with carboplatin and paclitaxel as first-line treatment for metastatic or recurrent nonsquamous NSCLC. A total of 642 patients were enrolled and randomized: 314 to the Avastin arm and 328 to the Mvasi arm. The objective of the study was to compare antitumor efficacy, safety, and immunogenicity. Risk ratio (RR) of objective response rate (ORR) (including complete or partial response) served as the primary end point.7,8
  • Per FDA requirements, the similarity margin for ORR was set at RR .73–1.36, equaling to ORR risk difference within 6% between arms. ORR occurred in 39% in the Mvasi group versus 41.7% in the Avastin group; primary end-point results showed no significant difference between groups: RR (95% confidence interval [CI]) 0.93 (.8-1.09); risk difference (90% CI) -2.9% (-9.26%–3.45%). No significant difference between groups was seen in magnitude of tumor response, progression-free survival, adverse effects, or immunogenicity.7,8

What role can the pharmacist play in the management of patients on bevacizumab-awwb?

  • Mvasi has the same dosing, adverse-event profile, and interactions that Avastin has.
  • Important warnings that require monitoring for the development of these issues include perforation or fistula formation, venous and arterial thrombotic events, hypertension, proteinuria, posterior reversible encephalopathy syndrome, and infusion reactions.4
  • Mvasi should be discontinued at least 28 days before elective surgery and withheld for at least 28 days after surgery and until the surgical site is fully healed.4
  • Gastrointestinal (GI) perforation is a serious adverse effect of bevacizumab products. GI perforation occurs in up to 3.2% of treated patients and is an indication for Mvasi cessation.4
  • Because of the risk of fatal bleeding, Mvasi should not be given to patients with a history of serious hemorrhage or recent hemoptysis.4
  • Mvasi should be temporarily suspended from treatment if severe hypertension (systolic greater than 180 mmHg or diastolic greater than 110 mmHg) occurs that cannot be controlled on antihypertensive agents.4 Blood pressure should be monitored regularly.4
  • Proteinuria and nephrotic syndrome can occur with bevacizumab-awwb.4 Dipstick urine analysis (UA) should be monitored frequently with 2+ or greater protein reading triggering a 24-hour urine collection.4 Mvasi should be discussed for greater than 2 g of proteinuria in 24 hours and resumed only when proteinuria returns to less than 2 g in 24 hours.4
  • In the phase 3 clinical trial comparing Mvasi to Avastin, important adverse events greater than grade 3 occurred in 102 of 324 patients (31.5%) in the experimental group versus 99 of 309 patients (32%) in the control group.7,8
  • Important grade 3 adverse events included7,8
    • neutropenia/infections: 16.7% (54/324) with Mvasi and 15.2% (47/309) with Avastin
    • hypertension: 6.8% (22/324) with Mvasi and 5.5% (17/309) with Avastin
    • venous and arterial thromboembolism: 3.7% (12/324) with Mvasi and 5.85% (15/309) with Avastin
    • GI perforation: 1.3% (4/324) with Mvasi and 1.3% (3/309) with Avastin
    • pulmonary hemorrhage: .6% (2/324) with Mvasi and 1.6% (5/309) with Avastin
    • infusion reactions: .6% (2/324) with Mvasi and .3% (1/324) with Avastin.

Clinical Pearls

  • Mvasi may replace Avastin in any of the above FDA indications. In addition, the biosimilar will likely be included in the other National Comprehensive Cancer Network (NCCN) compendium listings for Avastin, including these:9-13
    • first-line treatment of mCRC with a capecitabine-based regimen
    • combination with pemetrexed plus platinum-based chemotherapy agents for NSCLC
    • as a single agent or in combination with chemotherapy for anaplastic gliomas; in combination with chemotherapy for recurrent glioblastoma; as a single agent for recurrent ependymoma
    • second-line single-agent therapy for clear-cell RCC or use in non-clear-cell histology
    • first-line combination therapy with carboplatin and paclitaxel or second-line single-agent therapy for persistent, recurrent, or metastatic cervical cancer.
  • Mvasi is approved for its indications through an abbreviated licensure process as established in the Biologics Price Competition and Innovation Act of 2009, also known as the 351(k) pathway. Biosimilarity is demonstrated by structural and functional comparison to reference drug and animal studies and clinical studies for toxicity, pharmacokinetics/pharmacodynamics (PK/PD), immunogenicity, and clinical efficacy.14,15
  • As a biosimilar product, Mvasi cannot be automatically substituted for the reference drug as a generic drug can be substituted for a brand-name drug.14,15
  • U.S. patents for Avastin could prevent marketing for Mvasi until 2019. Therefore, cost information for comparing Mvasi with Avastin is not currently available.

References

  1. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011-1127.
  2. Keating GM. Bevacizumab: a review of its use in advanced cancer. Drugs. 2014;74:1891-1925.
  3. National Cancer Institute. FDA approval for bevacizumab. https://www.cancer.gov/about-cancer/treatment/drugs/fda-bevacizumab#Anchor-Metastati-43353. Updated December 4, 2014. Accessed October 10, 2017.
  4. Mvasi [package insert]. Thousand Oaks, CA: Amgen and Allergan; 2017.
  5. Thatcher N, Thomas M, Paz-Ares L, et. al. Randomized, double-blind, phase 3 study evaluating efficacy and safety of ABP 215 compared with bevacizumab in patients with non-squamous NSCLC. J Clin Oncol. 2016;34(15): 9095. doi: 10.1200/JCO.2016.34.15_suppl.9095
  6. Thatcher N, Thomas M, Ostoros G, et al. Secondary efficacy results from a phase 3 study comparing efficacy and safety of biosimilar candidate ABP 215 with bevacizumab in patients with non-squamous non-small cell lung cancer (NSCLC). Ann Oncol. 2016;27(Supplement 6):411-415. doi: 10.1093/annonc/mdw382.10.
  7. Amgen, Inc. FDA briefing document: ABP215, a proposed biosimilar to Avastin (bevacizumab). Food and Drug Administration. July 13, 2017. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM566365.pdf
  8. Amgen, Inc. Background information for the Oncologic Drugs Advisory Committee: biologics license application for ABP 215. Food and Drug Administration. July 13, 2017. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM566365.pdf
  9. NCCN clinical practice guidelines in oncology: non-small cell lung cancer. National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Updated September 28, 2017. Accessed October 12, 2017.
  10. NCCN clinical practice guidelines in oncology: cervical cancer. National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Updated October 10, 2016. Accessed October 12, 2017.
  11. NCCN clinical practice guidelines in oncology: kidney cancer. National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Updated September 7, 2017. Accessed October 12, 2017.
  12. NCCN clinical practice guidelines in oncology: central nervous system cancers. National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Updated August 18, 2017. Accessed October 12, 2017.
  13. NCCN clinical practice guidelines in oncology: colon cancer. National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Updated March 13, 2017. Accessed October 12, 2017.
  14. Food and Drug Administration. Scientific considerations in demonstrating biosimilarity to a reference product: guidance for industry. https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm290967.htm. April 28, 2015. Accessed October 10, 2017.
  15. Ventola CL. Biosimilars part 1: proposed regulatory criteria for FDA approval. PT. 2013; 38(5): 270-287.
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