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A Guide to Treatment

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A Guide to Treatment A Guide to Treatment While there are data in this guide that are found within the product labeling, this guide also includes data and information regarding potential management strategies from post hoc analyses that are not included in the product labeling, and are indicated as such throughout. 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. SELECTED SAFETY INFORMATION 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. Please see Important Safety Information on page 30. Please see Full Prescribing Information at VIZIMPROhcp.com. Table of contents Start the treatment plan with VIZIMPRO® (dacomitinib) ................................. Page 3 VIZIMPRO efficacy ............................................................................. Page 6 VIZIMPRO safety profile ...................................................................... Page 8 Dosing and administration ...................................................................Page 10 VIZIMPRO dose modifications and discontinuations in ARCHER 1050 ............Page 11 Proactively monitor .......................................................................Page 12 Dose adjust .................................................................................Page 14 Management strategies for common adverse reactions Diarrhea .....................................................................................Page 18 Stomatitis ...................................................................................Page 20 Rash ..........................................................................................Page 22 Dry skin ......................................................................................Page 24 Nail disorders...............................................................................Page 26 Resources for patients .......................................................................Page 28 Important Safety Information ...............................................................Page 30 Please see Important Safety Information on page 30. Please see Full Prescribing Information at VIZIMPROhcp.com. 2 Efficacy START THE TREATMENT PLAN WITH VIZIMPRO® (dacomitinib) 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.1 START IN FIRST LINE Start with VIZIMPRO 45 mg oral tablets1 PROACTIVELY MONITOR Proactively monitor patients to help manage potential adverse reactions1 DOSE ADJUST If needed, modify the dose. VIZIMPRO is available in 3 doses: 45 mg, 30 mg, 15 mg1 SELECTED SAFETY INFORMATION 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. Please see Important Safety Information on page 30. Please see Full Prescribing Information at VIZIMPROhcp.com. 3 START IN FIRST LINE VIZIMPRO® (dacomitinib) 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.1 Please see Important Safety Information on page 30. Please see Full Prescribing Information at VIZIMPROhcp.com. 4 ARCHER 1050 trial design1,2 Patients were randomized (1:1) to receive VIZIMPRO 45 mg (n=227) or gefitinib 250 mg (n=225) orally once daily until disease progression or unacceptable toxicity occurred.1 Patient population (N=452) Major efficacy outcome • Unresectable metastatic NSCLC with measure: Progression-free no prior therapy for metastatic disease, VIZIMPRO survival (PFS) as determined or recurrent disease with a minimum of 45 mg PO QD by blinded Independent 12 months disease-free after completion (n=227) Radiologic Central (IRC) of systemic therapy review per RECIST v1.1 • ECOG performance status of 0 or 1 1:1 • EGFR exon 19 deletion or exon 21 L858R Additional efficacy substitution mutations Gefitinib outcome measures: • Patients were excluded if they 250 mg PO QD PFS (investigator-assessed), had a history of interstitial lung (n=225) overall response rate (ORR) disease (ILD), interstitial pneumonitis, and duration of response or brain metastases (DOR) (per IRC), and overall survival (OS) Stratification factors1 • EGFR mutation status (exon 19 deletion vs exon 21 L858R substitution mutation) • Region (Japanese vs mainland Chinese vs other East Asian vs non-East Asian) In ARCHER 1050, subsequent systemic therapies for patients who progressed included chemotherapy, T790M inhibitors, and other agents.3 ECOG=Eastern Cooperative Oncology Group; EGFR=epidermal growth factor receptor; NSCLC=non-small cell lung cancer; PO=by mouth; QD=once a day; RECIST=Response Evaluation Criteria in Solid Tumors. SELECTED SAFETY INFORMATION 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. Please see Important Safety Information on page 30. Please see Full Prescribing Information at VIZIMPROhcp.com. 5 Efficacy VIZIMPRO® (dacomitinib) demonstrated superior progression-free survival (PFS) vs gefitinib1 VIZIMPRO reduced the risk of progression or death by 41% vs gefitinib (per IRC)1 1.0 0.9 VIZIMPRO VIZIMPRO demonstrated a median 5.5-MONTH 0.8 14.7 months I: IMPROVEMENT 1 0.7 in median PFS vs gefitinib 0.6 0.5 HR=0.59 0.4 I: P<0.0001 3 Gefitinib median Proaiit of Proressionree ria Proaiit of Proressionree 0.2 9.2 months I: 0.1 ensored atients 0.0 0 6 12 18 24 3 3 42 48 Proressionree ria Months er of atients at ris VIZIMPRO 227 154 106 3 20 6 0 0 0 Gefitinib 225 155 69 3 7 1 0 0 0 Median PFS by investigator assessment was 16.6 months in the VIZIMPRO arm (95% CI: 12.9-18.4) and 11.0 months in the gefitinib arm (95% CI: 9.4-12.1) (HR=0.62; 95% CI: 0.50-0.78).2 IRC=Independent Radiologic Central. SELECTED SAFETY INFORMATION 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. Please see Important Safety Information on page 30. Please see Full Prescribing Information at VIZIMPROhcp.com. 6 Efficacy VIZIMPRO additional efficacy outcomes in ARCHER 1050 The hierarchical statistical testing order was PFS followed by ORR and then OS. No formal testing of OS was conducted, Safety since the formal comparison of ORR was not statistically significant.1 Overall response rate (per IRC)1 Duration of response (per IRC)1 A similar percentage of patients responded Among responders, duration of response was longer in to treatment in each arm patients who were treated with VIZIMPRO vs gefitinib MEDIAN MEDIAN VIZIMPRO Gefitinib VIZIMPRO Gefitinib I: I: 75% 72% 14.8 I: 8.3 I: MONTHS MONTHS P =0.39 (Not statistically significant) The median OS for VIZIMPRO was 34.1 months1,3 The median represents a single point in time. It is important to consider the entire Kaplan-Meier curve when evaluating OS. Caution is required for the interpretation of descriptive OS results, as the hierarchical statistical testing procedure prevented formal assessment of the statistical significance of OS. This information should not be used to make comparisons between treatment arms. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 Overall SurvivalOverall Distribution Function 0.2 0.1 VIZIMPRO
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