MVASI® Indications

MVASI® is a vascular endothelial growth factor inhibitor indicated for the treatment of: MVASI®, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with metastatic colorectal cancer (mCRC).... Read More

BEHIND MVASI®

A ROBUST BIOSIMILARS PROGRAM

 
EXTRAPOLATION AND MVASI® MAPLE TRIAL DESIGN EFFICACY DATA SAFETY/ IMMUNOGENICITY DATA CLINICAL PK/ NONCLINICAL DATA

MVASI® WAS APPROVED BASED ON A TOTALITY OF EVIDENCE, INCLUDING A COMPARATIVE CLINICAL TRIAL1,2

The MAPLE trial: a large comparative clinical study (N = 642) that demonstrated the clinical similarity of MVASI® and Avastin® in non-squamous non-small cell lung cancer (NSCLC).1,*

MAPLE trial proved clinical similarity of MVASI® to
Avastin® MAPLE trial proved clinical similarity of MVASI® to
Avastin®

IV = intravenous;
Q3W = once every 3 weeks.

Patients remained on study for observation of disease progression and overall survival until the end of the study, withdrawal of consent, loss to follow-up, death, or until they received any other anticancer treatment such as maintenance therapy.1

*Patient population had either Stage 4 or recurrent metastatic non-squamous NSCLC with measurable disease according to RECIST v1.1, and initiated first-line carboplatin/paclitaxel.1

Patients remained on study for observation of disease progression and overall survival until the end of the study, withdrawal of consent, loss to follow-up, death, or until they received any other anticancer treatment such as maintenance therapy.1

*Patient population had either Stage 4 or recurrent metastatic non-squamous NSCLC with measurable disease according to RECIST v1.1, and initiated first-line carboplatin/paclitaxel.1


AMONG MVASI® INDICATIONS, NSCLC REPRESENTS A SENSITIVE STUDY POPULATION FOR SHOWING CLINICAL SIMILARITY1,3

PRIMARY ENDPOINT: RISK RATIO (RR) OF OBJECTIVE RESPONSE RATE (ORR)1,4

  • ORR offers a direct and objective measure of antitumor activity and has a strong correlation with tumor response and overall survival in NSCLC.
  • Equivalence is confirmed when the entire confidence interval (CI) for the primary endpoint (RR of ORR) falls within predefined margins.

KEY INCLUSION CRITERIA1

  • 18–79 years of age
  • Stage 4 or recurrent metastatic non-squamous NSCLC
  • Initiating first-line carboplatin/paclitaxel chemotherapy
  • ECOG PS 0-1
  • Adequate bone marrow, hepatic, and renal function

ECOG = Eastern Cooperative Oncology Group; PS = Performance Status.

Important Safety Information

Serious adverse reactions (Warnings and Precautions)

  • Serious and sometimes fatal adverse reactions with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
    • Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies
    • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
    • Arterial thromboembolic events (Grade ≥3, 5%, highest in patients with GBM)
    • The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in MVASI®-treated patients
    • Hemorrhage (Grade 3–5) ranged from 0.4% to 7% of patients across clinical studies
    • Renal injury and proteinuria
      • Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
      • Nephrotic syndrome (<1%)
  • Additional serious adverse reactions with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
    • Venous thromboembolism (Grade ≥3, 11% seen in GOG-0240)
    • Hypertension (Grade 3–4, 5%–18%)
    • Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
    • Congestive heart failure (CHF): Grade ≥3 left ventricular dysfunction (1%)
    • Infusion-related reactions with the first dose of bevacizumab occurred in <3% of patients, and severe reactions occurred in 0.4% of patients
  • Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
  • Inform females of reproductive potential of the risk of ovarian failure prior to initiating treatment with MVASI®

Pregnancy warning

  • Based on the mechanism of action and animal studies, MVASI® may cause fetal harm
  • Advise female patients that MVASI® may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
  • Advise females of reproductive potential to use effective contraception during treatment with MVASI® and for 6 months after the last dose of MVASI®
  • Advise nursing women not to breastfeed during treatment with MVASI® and for 6 months following their last dose of treatment
  • MVASI® may impair fertility

Most common adverse reactions

  • Across studies, the most common adverse reactions observed in bevacizumab patients at a rate >10% were:
    • Epistaxis
    • Headache
    • Hypertension
    • Rhinitis
    • Proteinuria
    • Taste alteration
    • Dry skin
    • Hemorrhage
    • Lacrimation disorder
    • Back pain
    • Exfoliative dermatitis
  • Across all studies, bevacizumab was discontinued in 8% to 22% of patients because of adverse reactions

Indication-specific adverse reactions

  • In CC, Grade 3 or 4 adverse reactions in Study GOG-0240, occurring at a higher incidence (≥2%) in 218 patients receiving bevacizumab plus chemotherapy compared to 222 patients receiving chemotherapy alone, were abdominal pain (12% vs 10%), diarrhea (6% vs 3%), anal fistula (4% vs 0%), proctalgia (3% vs 0%), urinary tract infection (8% vs 6%), cellulitis (3% vs 0.5%), fatigue (14% vs 10%), hypertension (11% vs 0.5%), thrombosis (8% vs 3%), hypokalemia (7% vs 4%), hyponatremia (4% vs 1%), dehydration (4% vs 0.5%), neutropenia (8% vs 4%), lymphopenia (6% vs 3%), back pain (6% vs 3%), and pelvic pain (6% vs 1%)
  • In mRCC, the most common Grade 3–5 adverse reactions in AVOREN, occurring at a >2% higher incidence in bevacizumab-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%, including hypertension and hypertensive crisis), and hemorrhage (3% vs 0.3%; including epistaxis, small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, hemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma)
  • In rGBM Study EORTC 26101, the incidence of Grade 3–4 VTE was 5% in patients receiving bevacizumab with chemotherapy compared to 2% in patients receiving chemotherapy alone. In this study, 22% of patients discontinued treatment in the bevacizumab with lomustine arm due to adverse reactions compared with 10% of patients in the lomustine arm. In patients receiving bevacizumab with lomustine, the adverse reaction profile was similar to that observed in other approved indications
  • In NSCLC, Grade 3–5 (nonhematologic) and Grade 4–5 (hematologic) adverse reactions in Study E4599 occurring at a ≥2% higher incidence in bevacizumab-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thromboembolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with Grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)
  • In first-line MCRC, the most common Grade 3–4 reactions in Study 2107, which occurred at a ≥2% higher incidence in the bevacizumab plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)
  • In second-line MCRC, the most common Grade 3–5 (nonhematologic) and 4–5 (hematologic) reactions in Study E3200, which occurred at a higher incidence (≥2%) in the bevacizumab plus FOLFOX4 vs FOLFOX4 groups, were fatigue (19% vs 13%), diarrhea (18% vs 13%), sensory neuropathy (17% vs 9%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), hypertension (9% vs 2%), abdominal pain (8% vs 5%), hemorrhage (5% vs 1%), other neurological (5% vs 3%), ileus (4% vs 1%), and headache (3% vs 0%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study
  • When continued beyond first progression in MCRC, no new safety signals were observed in the TML study (ML18147) when bevacizumab was administered in second-line MCRC patients who progressed on a bevacizumab containing regimen in first-line MCRC. The safety data was consistent with the known safety profile established in first- and second-line MCRC

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Amgen at 1-800-772-6436.

Please see full Prescribing Information for additional Important Safety Information.

INDICATIONS

MVASI® is a vascular endothelial growth factor inhibitor indicated for the treatment of:

MVASI®, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with metastatic colorectal cancer (mCRC).

MVASI®, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product-containing regimen.

Limitations of Use: MVASI® is not indicated for adjuvant treatment of colon cancer.

MVASI®, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC).

MVASI® is indicated for the treatment of recurrent glioblastoma (GBM) in adults.

MVASI®, in combination with interferon-alfa, is indicated for the treatment of metastatic renal cell carcinoma (mRCC).

MVASI®, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer (CC).

Avastin® (bevacizumab) is a registered trademark of Genentech USA, Inc.

MVASI® Important Safety Information

Serious adverse reactions (Warnings and Precautions)

  • Serious and sometimes fatal adverse reactions with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
    • Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies

References: 1. Thatcher N, Goldschmidt JH, Thomas M, et al. Efficacy and safety of the biosimilar ABP 215 compared with bevacizumab in patients with advanced nonsquamous non-small cell lung cancer (MAPLE): a randomized, double-blind, phase III study. Clin Cancer Res. 2019;25:2088-2095. 2. MVASI® (bevacizumab-awwb) Prescribing Information, Amgen. 3. US Food and Drug Administration. ODAC briefing document: ABP 215, a proposed biosimilar to US-Avastin. BLA 761028. July 13, 2017. 4. Data on file, Amgen; 2015 [CSR 20120265].