Patient Characteristics & Treatment Considerations

Patient Characteristics & Treatment Considerations
From the AXIS trial: an open-label, phase 3 trial in metastatic RCC following one prior systemic therapy (N=723)
*
PROGRESSION-FREE SURVIVAL (PFS): PRIMARY ENDPOINT
OBJECTIVE RESPONSE RATE (ORR): SECONDARY ENDPOINT
OVERALL SURVIVAL (OS): SECONDARY ENDPOINT
*From AXIS, a multicenter, open-label, phase 3 trial of 723 patients with metastatic RCC (mRCC) after failure of 1st-line therapy (sunitinib-, temsirolimus-, bevacizumab-, or cytokine-containing regimen [54%, 3%, 8%, and 35% of patients in each of the treatment arms, respectively]). Patients were randomized 1:1 to either INLYTA 5 mg twice daily (n=361) or sorafenib 400 mg twice daily (n=362), with dose adjustments allowed in both groups. Primary endpoint was PFS. Secondary endpoints included ORR, OS, and safety and tolerability.1,2
References: 1. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931-1939. 2. Data on file. Pfizer Inc, New York, NY.
In the phase 3 AXIS trial
*
  • 9% of patients discontinued INLYTA® (axitinib) (n=34/359) due to AEs vs 13% of patients with sorafenib (n=46/355)
  • Overall, 61% of patients receiving INLYTA discontinued treatment vs 71% receiving sorafenib1
    —In both study groups, the most common reasons for discontinuation included disease progression or relapse and AEs
  • Fewer patients receiving INLYTA had dose modifications or temporary delay of treatment due to AEs compared with patients receiving sorafenib (55% vs 62%, respectively)
*From AXIS, a multicenter, open-label, phase 3 trial of 723 patients with metastatic RCC (mRCC) after failure of 1st-line therapy (sunitinib-, temsirolimus-, bevacizumab-, or cytokine-containing regimen [54%, 3%, 8%, and 35% of patients in each of the treatment arms, respectively]). Patients were randomized 1:1 to either INLYTA 5 mg twice daily (n=361) or sorafenib 400 mg twice daily (n=362), with dose adjustments allowed in both groups. Primary endpoint was PFS. Secondary endpoints included ORR, OS, and safety and tolerability.1,2
MOST COMMON ADVERSE EVENTS
The most common (≥20%) adverse events (AEs) occurring in patients receiving INLYTA (all grades, vs sorafenib) were diarrhea (55% vs 53%), hypertension (40% vs 29%), fatigue (39% vs 32%), decreased appetite (34% vs 29%), nausea (32% vs 22%), dysphonia (31% vs 14%), hand-foot syndrome (27% vs 51%), weight decreased (25% vs 21%), vomiting (24% vs 17%), asthenia (21% vs 14%), and constipation (20% vs 20%).
The most common (≥10%) grade 3/4 AEs occurring in patients receiving INLYTA (vs sorafenib) were hypertension (16% vs 11%), diarrhea (11% vs 7%), and fatigue (11% vs 5%).
In a pooled, retrospective, long-term safety study (N=672)
3†
  • Data from the study indicate that long-term treatment with INLYTA (≥2 years) was not associated with unanticipated AEs; some AEs increased over time (proteinuria, increased blood creatinine, and peripheral edema)3
  • It is important to evaluate and manage risk factors for myocardial infarction and increased amylase3
  • In the AXIS trial, the median duration of treatment was 6.4 months (range 0.03-22.0) and 5 months (range 0.03-20.1) for INLYTA and sorafenib, respectively
From a retrospective study that analyzed pooled data from 5 clinical trials (phase 3 and phase 2), including AXIS, in patients (N=672) with previously treated mRCC. In one study, patients may have received one or more previous systemic treatments; the remaining 4 trials examined patients who had received one previous 1st-line regimen.3
In a retrospective analysis of real-world data
4‡
  • 68% of patients maintained their starting dose and 12% increased from their starting dose
From a retrospective, observational, cohort study (N=1175) using the Specialty Pharmacy Data Mart, an IMS®-managed database containing data from a limited distribution network of 22 specialty pharmacies (regional and national) that dispense INLYTA, for first prescriptions dispensed between May 2012 and April 2013. 659/1175, or 56% of patients, were prescribed INLYTA after one prior systemic therapy. For these patients, the mean daily dose of INLYTA over treatment duration was 10.3 mg.4
Study limitations4
  • Data from medical and pharmacy claims have inherent limitations: Claims data are collected for billing and reimbursement purposes rather than research objectives—causality cannot be inferred
  • Clinical outcomes (such as survival) were not addressed
For further study limitations, please see MacLean E, Cisar L, Mehle K, Eremina D, Quigley JM. Real-world axitinib use in the United States: a retrospective study using linked datasets. J Manag Care Spec Pharm. 2016;22(6):723-732u.
References: 1. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931-1939. 2. Data on file. Pfizer Inc, New York, NY. 3. Rini BI, Escudier B, Hariharan S, et al. Long-term safety with axitinib in previously treated patients with metastatic renal cell carcinoma. Clin Genitourin Cancer. 2015;13(6):540-547. 4. MacLean E, Cisar L, Mehle K, Eremina D, Quigley JM. Real-world axitinib use in the United States: a retrospective study using linked datasets. J Manag Care Spec Pharm. 2016;22(6):723-732u.
From the AXIS trial: an open-label, phase 3 trial in mRCC following one prior systemic therapy (N=723)*
PRIMARY ENDPOINT: PROGRESSION-FREE SURVIVAL (PFS) IN THE OVERALL STUDY POPULATION
PFS in the overall study population
SUBGROUP ANALYSES
INLYTA nearly doubled median PFS (mPFS) after progression on 1st-line cytokine-based immunotherapy (IL-2 or IFN-α)
Improvement in PFS among patients previously treated with cytokine-based immunotherapy (IL-2 or IFN-α): from a prespecified subset analysis of the phase 3 AXIS trial1
  • 35% of patients in the AXIS trial had previously been treated with IL-2 or IFN-α
    — Prior therapies for other patients in the trial contained sunitinib (54%), bevacizumab (8%), or temsirolimus (3%)
  • The cytokine-based immunotherapies IL-2 and IFN-α were the most common 1st-line immunotherapies used at the time of the AXIS trial, for which registration concluded in 2010
INLYTA prolonged mPFS after progression on sunitinib
In another prespecified subset analysis of the phase 3 AXIS trial, INLYTA prolonged mPFS after progression on sunitinib
  • 4.8 months mPFS (95% CI: 4.5, 6.4) with INLYTA (n=194) vs 3.4 months (95% CI: 2.8, 4.7) with sorafenib (n=195) (HR=0.74 [95% CI: 0.57, 0.96]); P value is not included because there was no adjustment for multiple testing
*From AXIS, a multicenter, open-label, phase 3 trial of 723 patients with metastatic RCC after failure of 1st-line therapy (sunitinib-, temsirolimus-, bevacizumab-, or cytokine-containing regimen [54%, 3%, 8%, and 35% of patients in each of the treatment arms, respectively]). Patients were randomized 1:1 to either INLYTA 5 mg twice daily (n=361) or sorafenib 400 mg twice daily (n=362), with dose adjustments allowed in both groups. Primary endpoint was PFS. Secondary endpoints included objective response rate, overall survival, and safety and tolerability.1,2
References: 1. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931-1939. 2. Data on file. Pfizer Inc, New York, NY.
DISTRIBUTION OF PATIENTS BY RISK STATUS IN THE PHASE 3 AXIS TRIAL1*
  • 45% of patients in the AXIS trial had an ECOG performance status of 1; 55% had an ECOG performance status of 0
From AXIS, a multicenter, open-label, phase 3 trial of 723 patients with mRCC after failure of 1st-line therapy (sunitinib-, temsirolimus-, bevacizumab-, or cytokine-containing regimen [54%, 3%, 8%, and 35% of patients in each of the treatment arms, respectively]). Patients were randomized 1:1 to either INLYTA® (axitinib) 5 mg twice daily (n=361) or sorafenib 400 mg twice daily (n=362), with dose adjustments allowed in both groups. Primary endpoint was PFS. Secondary endpoints included ORR, OS, and safety and tolerability.1,2
References: 1. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931-1939. 2. Data on file. Pfizer Inc, New York, NY.
THE AXIS TRIAL INCLUDED PATIENTS WITH A VARIETY OF METASTATIC SITES AT BASELINE1
  • Additional sites in patients receiving INLYTA (vs sorafenib) included pleural effusion (5.0% vs 5.0%), ascites (0.6% vs 1.4%), pancreas (2.2% vs 2.8%), spleen (3.9% vs 2.8%), pelvis (3.0% vs 1.1%), peritoneum (7.2% vs 8.3%), and other (38.5% vs 35.9%)
Reference: 1. Data on file. Pfizer Inc, New York, NY.
  • INLYTA® (axitinib) has a short half-life of 2.5 to 6.1 hours
Pharmacokinetics of INLYTA1*
  • Based on the plasma half-life, steady state for INLYTA is expected within 2 to 3 days
Reference: 1. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol. 2005;23(24):5474-5483.
  • INLYTA® (axitinib) may be taken with or without food
  • Patients should not eat grapefruit, drink grapefruit juice, or take St John's wort while taking INLYTA
ORAL ADMINISTRATION AND DOSING 
  • INLYTA® (axitinib) may be taken with or without food
  • Patients should not eat grapefruit, drink grapefruit juice, or take St. John's wort while taking INLYTA
  • Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the dose. Grapefruit or grapefruit juice may also increase INLYTA plasma concentrations and should be avoided
  • Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate CYP3A4/5 inducers
Dosing recommendations
  • The recommended starting dose of INLYTA is 5 mg twice daily
  • For patients with moderate hepatic impairment (Child-Pugh class B) or those concomitantly receiving a strong CYP3A4/5 inhibitor, reduce the starting dose by approximately half
  • Dose adjustments can be made based on individual safety and tolerability
  • Administer doses approximately 12 hours apart
  • Swallow whole with a glass of water
  • May be taken with or without food
Dose titration
Management of some AEs may require temporary interruption or permanent discontinuation and/or dose reduction.
If a dose reduction from the starting dose is required:
  • Reduce dose to 3 mg twice daily
  • Reduce dose to 2 mg twice daily if additional dose reduction is required
Dose increase criteria:
  • Patients tolerate INLYTA for at least 2 consecutive weeks with no AEs >grade 2 and are normotensive without hypertension medication
  • Dose may be increased to 7 mg twice daily if patients meet dose increase criteria at the starting dose
  • Dose may be further increased to 10 mg twice daily if patients meet the dose increase criteria at the 7-mg dose