Response Data

In activating HER2-mutant 2L mNSCLC at 5.4 mg/kg

The majority of patients treated with ENHERTU achieved a durable response1

Confirmed objective response rate1,a,b

Bar graph of confirmed objective response rate (57.7%) of ENHERTU from DESTINY-Lung02 Bar graph of confirmed objective response rate (57.7%) of ENHERTU from DESTINY-Lung02

Median duration of response1,a,c

Bar graph of median duration of response (8.7 months) of ENHERTU from DESTINY-Lung02 Bar graph of median duration of response (8.7 months) of ENHERTU from DESTINY-Lung02
  • The cutoff date for efficacy data was June 22, 2022

CI, confidence interval; CR, complete response; HER2, human epidermal growth factor receptor 2; mDOR, median duration of response; NE, not evaluable; ORR, objective response rate; PR, partial response; SD, stable disease.

aRadiographic tumor assessments were performed every 6 weeks.1

bConfirmed objective response was assessed by BICR based on RECIST v1.1. ORR 95% CI calculated using Clopper-Pearson method.1

cMedian DOR based on Kaplan-Meier estimate; 95% CI calculated using Brookmeyer-Crowley method.1

Confirmed objective response was assessed by independent central review on the basis of the Response Evaluation Criteria in Solid Tumors, version 1.1.

ENHERTU was evaluated at two dose levels. While response rates were consistent across dose levels, increased rates of ILD/pneumonitis were observed at the higher dose in patients with NSCLC. The approved recommended dose of 5.4 mg/kg IV Q3W is described above1

Adverse Reactions

ENHERTU has serious Warnings and Precautions. Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

In activating HER2-mutant 2L mNSCLC at 5.4 mg/kg

The majority of adverse reactions observed with ENHERTU were Grade 21

Only the results for the recommended dose of 5.4 mg/kg are described due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.1

  • 19% of the 101 patients treated with ENHERTU in DESTINY-Lung02 were exposed for >6 months1
  • The cutoff date for safety data was March 24, 20222

Common (10% all Grades or 2% Grades 3-4) adverse reactions in DESTINY-Lung021,2

Events were graded using NCI-CTCAE v.5.0.

dIncluding vomiting and retching.

eIncluding mucosal inflammation and stomatitis.

fIncluding asthenia, fatigue, and malaise.

gIncluding back pain, musculoskeletal stiffness, musculoskeletal chest pain, arthralgia, musculoskeletal pain, myalgia, and pain in extremity.

Serious adverse reactions occurred in 30% of patients receiving ENHERTU1

  • Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin
  • Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%)

Adverse reactions requiring dose discontinuation, interruption, or reduction of ENHERTU in DESTINY-Lung021

Selected laboratory abnormalities in patients in DESTINY-Lung021

hPercentages were calculated using patients with worsening laboratory values from baseline and the number of patients with both baseline and post-treatment measurements as the denominator.

iFrequencies were based on NCI-CTCAE v.5.0 grade-derived laboratory abnormalities.

jThe denominator used to calculate the rate varied from 98 to 99 based on the number of patients with a baseline value and at least 1 post-treatment value.

Other clinically relevant adverse reactions reported in <10% of patients receiving ENHERTU1

  • Respiratory, thoracic and mediastinal disorders: ILDk (6%), dyspnea (5%), and epistaxis (3%)
  • Gastrointestinal disorders: abdominal painl (9%)
  • Skin and subcutaneous disorders: rashm (3%)
  • Infections and infestations: upper respiratory tract infectionn (4%)
  • Nervous system disorders: headacheo (4%)

kIncluding ILD that was adjudicated as ILD including pneumonitis, ILD, pulmonary toxicity, and respiratory failure.

lIncluding abdominal discomfort, abdominal pain, and upper abdominal pain.

mIncluding rash and rash maculopapular.

nIncluding upper respiratory tract infection, pharyngitis, and laryngitis.

oIncluding headache and migraine.

Drug interaction studies1

  • Clinical studies: There were no clinically meaningful drug-drug interactions between ENHERTU and itraconazole (CYP3A inhibitor), or ritonavir (OATP inhibitor)
  • In vitro studies: DXd did not inhibit common CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A) nor did it induce CYP1A2, CYP2B6, or CYP3A
  • In vitro studies: At clinically relevant concentrations, DXd has a low potential to inhibit the transporters OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, MATE1, MATE2-K, P-gp, BCRP, or BSEP
  • In vitro studies: DXd is a substrate of OATP1B1, OATP1B3, MATE2-K, P-gp, MRP1, and BCRP

Interstitial Lung Disease (ILD) and Pneumonitis

Symptom identification and investigation at the first sign of ILD/pneumonitis are key to diagnosis and monitoring

ENHERTU given at a higher dose than 5.4 mg/kg is associated with increased toxicity in patients with NSCLC, including ILD/pneumonitis1

Signs and symptoms of ILD/pneumonitis1

  • Cough
  • Dyspnea
  • Fever
  • New or worsening respiratory symptoms

Promptly investigate evidence of ILD/pneumonitis3

  • Diagnosis of ILD/pneumonitis requires exclusion of other causes
  • Evaluation may include:
    • High-resolution CT
    • Pulmonologist consultation
    • Blood culture and CBC
  • All events of ILD/pneumonitis, regardless of severity or seriousness, should be followed until resolution, including after drug discontinuation
  • Advise patients of the potential benefits and risks of treatment and to contact their HCP immediately to report any of these symptoms

CBC, complete blood count; CT, computed tomography.

A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment1

Investigation may be prompted by incidental findings on routine scans when checking for progression or symptomatic findings

For asymptomatic ILD/pneumonitis (Grade 1)1

  • Consider corticosteroid treatment (eg, ≥0.5 mg/kg/day prednisolone or equivalent)
  • Interrupt ENHERTU until resolved to Grade 0, then:

For symptomatic ILD/pneumonitis (Grade 2 or greater)1

  • Promptly initiate systemic corticosteroid treatment (eg, ≥1 mg/kg/day prednisolone or equivalent)
    • Continue for at least 14 days followed by gradual taper for at least 4 weeks
  • Permanently discontinue ENHERTU in patients who are diagnosed with any symptomatic ILD/pneumonitis

Talk to your patients to raise awareness and help identify symptoms

  • Advise patients to contact their healthcare provider immediately for any of the symptoms shown above
  • Inform patients of the risks of severe, life-threatening, or fatal ILD
  • Advise patients to read the FDA-approved patient labeling: Download the Medication Guide

Potential questions to ask your patients to help with identification of ILD4,5

  • Have you been coughing recently? Is it a dry cough?
  • Have you had any shortness of breath, especially during or after physical activity?
  • Have you experienced any new breathing or respiratory problems?
  • If you already have respiratory problems, have they gotten worse?
  • Have you had a fever?
  • Have you been feeling tired?
  • Have you lost weight?

See complete Prescribing Information for further details regarding recommended dosage modifications for adverse reactions.