​​​​​​​Safety Profile

Warnings and Precautions

The data in the Warnings and Precautions section reflect exposure to VIZIMPRO in 394 patients with EGFR exon 19 deletion or exon 21 L858R substitution mutations (including those who were treatment-naive and those who had received prior treatment) who received VIZIMPRO at the recommended dose of 45 mg once daily in 4 randomized, active-controlled trials (ARCHER 1050 [N=227], Study A7471009 [N=38], Study A7471011 [N=83], and Study A7471028 [N=16]) and one single-arm trial (Study A7471017 [N=30]). The median duration of exposure to VIZIMPRO was 10.8 months (0.07-68 months).

Interstitial lung disease (ILD)2

  • Severe and fatal ILD/pneumonitis occurred in patients treated with VIZIMPRO and occurred in 0.5% of the 394 VIZIMPRO-treated patients; 0.3% of cases were fatal
  • Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold VIZIMPRO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms that may be indicative of ILD (eg, dyspnea, cough, and fever). Permanently discontinue VIZIMPRO if ILD is confirmed

Diarrhea2

  • Severe and fatal diarrhea occurred in patients treated with VIZIMPRO. Diarrhea occurred in 86% of the 394 VIZIMPRO-treated patients; Grade 3 or 4 diarrhea was reported in 11% of patients and 0.3% of cases were fatal
  • Withhold VIZIMPRO for Grade 2 or greater diarrhea until recovery to Grade ≤1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of diarrhea
  • Promptly initiate antidiarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea

Dermatologic adverse reactions2

  • Rash and exfoliative skin reactions occurred in patients treated with VIZIMPRO. Rash occurred in 78% of the 394 VIZIMPRO-treated patients; Grade 3 or 4 rash was reported in 21% of patients. Exfoliative skin reactions of any severity were reported in 7% of patients. Grade 3 or 4 exfoliative skin reactions were reported in 1.8% of patients
  • Withhold VIZIMPRO for persistent Grade 2 or any Grade 3 or 4 dermatologic adverse reaction until recovery to Grade ≤1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of the dermatologic adverse reaction
  • The incidence and severity of rash and exfoliative skin reactions may increase with sun exposure. At the time of initiation of VIZIMPRO, initiate use of moisturizers and appropriate measures to limit sun exposure
  • Upon development of Grade 1 rash, initiate treatment with topical antibiotics and topical steroids. Initiate oral antibiotics for Grade 2 or more severe dermatologic adverse reactions

Embryo-fetal toxicity2

  • Based on findings from animal studies and its mechanism of action, VIZIMPRO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of dacomitinib to pregnant rats during the period of organogenesis resulted in an increased incidence of post-implantation loss and reduced fetal body weight at doses resulting in exposures near the exposure at the 45 mg human dose
  • The absence of EGFR signaling has been shown to result in embryolethality as well as post-natal death in animals. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with VIZIMPRO and for at least 17 days after the final dose
Adverse Reactions

The safety profile of VIZIMPRO was established in the ARCHER 1050 trial

Adverse reactions in ≥10% of VIZIMPRO-treated patients2†

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​​​​​​​   †National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03.

​​​​​​​   aGrades 1 through 5 are included in All Grades.

​​​​​​​   bOne Grade 5 (fatal) event in the VIZIMPRO arm.

​​​​​​​   cStomatitis includes mucosal inflammation and stomatitis.

​​​​​​​   dRash includes dermatitis acneiform, rash, and rash maculo-papular.

​​​​​​​   eParonychia includes nail infection, nail toxicity, onychoclasis, onycholysis, onychomadesis, paronychia.​​​​​​​

​​​​​​​   fDry skin includes dry skin, xerosis.

​​​​​​​   gPruritus includes pruritus, pruritus generalized, rash pruritic.

​​​​​​​   hNasal mucosal disorder includes epistaxis, nasal inflammation, nasal mucosal disorder, nasal mucosal ulcer, rhinitis.​​​​​​​​​​​​​​


The majority of adverse reactions were Grade 1 or 2 in severity.​​​​​​​

Additional adverse reactions (all Grades) with VIZIMPRO2:

  • ​​​​​​​General: fatigue 9%
  • Skin and subcutaneous tissue: skin fissures 9%, hypertrichosis 1.3%, skin exfoliation/exfoliative skin reactions 3.5%
  • Gastrointestinal: vomiting 9%
  • Nervous system: dysgeusia 7%
  • Respiratory: interstitial lung disease 2.6%
  • Ocular: keratitis 1.8%
  • Metabolism and nutrition: dehydration 1.3%

Most common adverse reactions with VIZIMPRO

The most common (>20%) adverse reactions in patients treated with VIZIMPRO were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%). The most common (≥1%) serious adverse reactions were diarrhea (2.2%) and interstitial lung disease (1.3%).2

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Laboratory Abnormalities

​​​​​​​Laboratory abnormalities worsening from baseline in >30% of patients2‡  

Laboratory abnormalities worsening from baseline in >30% of patients (all Grades VIZIMPRO % vs gefitinib %): anemia (44 vs 26), lymphopenia (42 vs 35), hypoalbuminemia (44 vs 34), increased ALT (40 vs 63), hyperglycemia (36 vs 38), increased AST (35 vs 57), and hypocalcemia (33 vs 28).

NCI CTCAE v4.03.
​​​​​​​

Dose Modifications and Discontinuations

In some patients, VIZIMPRO dose modifications helped to manage adverse reactions without the need for permanent discontinuation while maintaining efficacy3,4

Median PFS in dose-reduced patients (n=150) was 16.6 months (95% CI: 14.6-18.6) (by IRC)4

** This is an optional area where footnotes can live.

ALT=alanine aminotransferase; AST=aspartate aminotransferase; PFS=progression-free survival.
​​​​​​


References:
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed June 3, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. VIZIMPRO Prescribing Information. New York, NY: Pfizer Inc.
  3. Zhou Q, Wu YL, Corral J, et al. Management of common adverse events related to first-line dacomitinib use in EGFR mutation-positive non-small-cell lung cancer: a pooled safety analysis [published online March 6, 2019]. Future Oncol. 2019;15(13):1481-1491. doi:10.2217/fon-2018-0944.
  4. Corral J, Mok TS, Nakawaga K, et al. Effects of dose modifications on the safety and efficacy of dacomitinib for EGFR mutation-positive non-small-cell lung cancer. Future Oncol. 2019;15(24):2795-2805.

Efficacy & Safety

  • Efficacy
  • Safety Profile
  • Study Design
View Support & Services

Dacomitinib (VIZIMPRO) is a National Comprehensive Cancer Network® (NCCN®) recommended treatment option1*

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend dacomitinib (VIZIMPRO) as one of the first-line options for sensitizing EGFR-positive metastatic NSCLC (Category 1)​​​​​​​1

Learn more

*The NCCN Guidelines® for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays.

There are no contraindications for VIZIMPRO

Interstitial Lung Disease (ILD): Severe and fatal ILD/pneumonitis occurred in patients treated with VIZIMPRO and occurred in 0.5% of the 394 VIZIMPRO-treated patients; 0.3% of cases were fatal. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold VIZIMPRO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue VIZIMPRO if ILD is confirmed.

Diarrhea: Severe and fatal diarrhea occurred in patients treated with VIZIMPRO. Diarrhea occurred in 86% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 diarrhea was reported in 11% of patients and 0.3% of cases were fatal. Withhold VIZIMPRO for Grade 2 or greater diarrhea until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of diarrhea. Promptly initiate anti-diarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea.

Dermatologic Adverse Reactions: Rash and exfoliative skin reactions occurred in patients treated with VIZIMPRO. Rash occurred in 78% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 rash was reported in 21% of patients. Exfoliative skin reactions of any severity were reported in 7% of patients. Grade 3 or 4 exfoliative skin reactions were reported in 1.8% of patients. Withhold VIZIMPRO for persistent Grade 2 or any Grade 3 or 4 dermatologic adverse reaction until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of the dermatologic adverse reaction. The incidence and severity of rash and exfoliative skin reactions may increase with sun exposure. At the time of initiation of VIZIMPRO, initiate use of moisturizers and appropriate measures to limit sun exposure. Upon development of Grade 1 rash, initiate treatment with topical antibiotics and topical steroids. Initiate oral antibiotics for Grade 2 or more severe dermatologic adverse reactions.

Embryo-Fetal Toxicity: VIZIMPRO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with VIZIMPRO and for at least 17 days after the final dose.

Adverse Reactions: The most common (>20%) adverse reactions were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%). The most common (≥1%) serious adverse reactions were diarrhea (2.2%) and interstitial lung disease (1.3%).

Drug Interactions: Concomitant use with a proton pump inhibitor (PPI) decreases dacomitinib concentrations, which may reduce VIZIMPRO efficacy. Avoid the concomitant use of PPIs with VIZIMPRO. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer VIZIMPRO at least 6 hours before or 10 hours after taking an H2-receptor antagonist. Concomitant use of VIZIMPRO increases the concentration of drugs that are CYP2D6 substrates which may increase the risk of toxicities of these drugs. Avoid concomitant use of VIZIMPRO with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

Lactation: Because of the potential for serious adverse reactions in breastfed infants from VIZIMPRO, advise women not to breastfeed during treatment with VIZIMPRO and for at least 17 days after the last dose.

Geriatric: Exploratory analyses suggest a higher incidence of Grade 3/4 adverse reactions and more frequent dose interruptions and discontinuations for adverse reactions in patients 65 years or older.

Renal Impairment: No dose modification is recommended for patients with mild or moderate renal impairment. The recommended dose of VIZIMPRO has not been established for patients with severe renal impairment (CLcr <30 mL/min).

Hepatic Impairment: No dose modification is recommended in patients with mild, moderate or severe hepatic impairment. 

VIZIMPRO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.

Please see Full Prescribing Information for VIZIMPRO.

Indication

VIZIMPRO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.

Please see Full Prescribing Information for VIZIMPRO.