Experts in your region share their experience with ALUNBRIG® (brigatinib)
Mohammad Jahanzeb, MD, FACP, FASCO
President, OncAdvisor
Creative Precision Oncology
Boca Raton, Florida
Learn the Facts About ALK+ mNSCLC in the USa
Every 2.4 minutes in the US, someone is diagnosed with lung cancer.1,b Each year, an estimated 180,697 people are diagnosed with NSCLC in the US,1,2,c and about 7,228 of them have ALK+ NSCLC.1-3,d
Of the estimated 7,228 patients diagnosed with ALK+ NSCLC each year, about 90% of these cases are metastatic.1-4
aIncidence data is for lung and bronchus cancer 2016-2020 and is age-adjusted to the 2000 US standard population. Data as of December 2022 reported by NAACCR as meeting high quality standards for 2016-2020 and include data from state and provincial cancer registries participating in SEER, NPCR, or both, in the US and the Canadian Cancer Registry in Canada.
bBased on 223,083 national annual incidence average 2016-2020 vs 525,000 minutes per year.
cEstimated using national estimate of 81% lung cancer cases being NSCLC.2
dEstimated using national estimate of 81% lung cancer cases being NSCLC2 and 4% of ALK-positive lung cancer.3
Systemic Efficacy for Patients Diagnosed With ALK+ mNSCLC
ALUNBRIG Doubled Median PFS vs Crizotinib in ALTA 1L7
Investigator assessed: 29.4 months median PFS for ALUNBRIG vs 9.2 months for crizotinib (HR=0.43; 95% CI: 0.31, 0.61; P<0.0001)6,b
aStratified by presence of brain metastases at baseline and prior chemotherapy for locally advanced or metastatic disease for log-rank test and Cochran Mantel-Haenszel test, respectively.7
bInvestigator-assessed PFS did not include a formal hypothesis test with Type I error control. In addition, ALTA 1L was an open-label trial, so there may be bias that contributed to the estimation of benefit from the investigator-assessed PFS.
A Treatment That Offers High Response Rates and Durable Responses7
ALUNBRIG Demonstrated High Response Rates and Durable Responses in the ITT Population7
aStratified by presence of brain metastases at baseline and prior chemotherapy for locally advanced or metastatic disease for log-rank test and Cochran Mantel-Haenszel test, respectively.7
Serious adverse reactions occurred in 33% of patients receiving ALUNBRIG.7
The most common serious adverse reactions in ALTA 1L were7:
- Pneumonia (4.4%)
- ILD/pneumonitis (3.7%)
- Pyrexia (2.9%)
- Dyspnea (2.2%)
- Pulmonary embolism (2.2%)
- Asthenia (2.2%)
Fatal adverse reactions occurred in 2.9% of patients and included7:
- Pneumonia (1.5%)
- Cerebrovascular accident (0.7%)
- Multiple organ dysfunction syndrome (0.7%)
Secondary Endpoint: ALUNBRIG Delayed Time to Worsening in Global Health Status (GHS)/Quality of Life (QoL)6
Time to worsening was assessed by physical, emotional, cognitive, and social functioning scales as well as improvement of disease symptoms.6
Study Limitations: These patient-reported outcome endpoints were exploratory and not prespecified. The improvement in QoL scores and delay in worsening of GHS/QoL may be an overestimation, because patients were not blinded to treatment assignment.
- These differences in global QoL could reflect differences in efficacy on disease-related symptoms and in treatment-related adverse events6
Among responders, the median duration of improvement in QoL had not been reached for ALUNBRIG vs 12 months for crizotinib.6
aPatient-reported symptoms, functioning, and GHS/QoL were measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and supplemental QLQ-LC13 (Lung Cancer Module).
Final Analysis With 40.4 Months of Median Follow-up in the ITT Population8
- Median DOR was nearly 20 months longer with ALUNBRIG vs crizotinib7
Overall Survival7
Median OS not reached for either arm7:
- 30% of patients (n=41/137) died in the ALUNBRIG® (brigatinib) arm vs 37% of patients (n=51/138) in the crizotinib arm5,8
- The 3-year OS rate was 71% (95% CI: 62, 78) with ALUNBRIG and 68% (95% CI: 59, 75) with crizotinib (HR=0.81; 95% Cl: 0.53, 1.22; P=0.331)8
47% of patients (n=65) in the crizotinib arm had crossed over to receive ALUNBRIG.8
Learn more about the ALTA 1L trial design
Choose an ALK+ mNSCLC First-Line Treatment With Proven Intracranial Efficacy
Brain Metastases Population (FINAL ANALYSIS WITH 40.4 MONTHS OF MEDIAN FOLLOW-UP)
Intracranial PFS in Patients with Any Brain Metastases at Baseline8
Intracranial PFS was defined as the time interval from the date of randomization until the first date at which CNS disease progression was objectively documented or death due to any cause, whichever occurred first.5
Study Limitation: ALTA 1L was not powered to detect differences across subgroups; results are presented descriptively.
° The HR for intracranial PFS in patients who did not have brain metastases at baseline was 0.703 (95% CI: 0.39, 1.26)9
Based on a post hoc subgroup analysis of ALTA 1L,
In Patients with Brain Metastases at Baselinea, the Intracranial Response Rate for ALUNBRIG was 3 Times Higher than Crizotinib7
BIRC-assessed confirmed intracranial ORR and intracranial DOR according to RECIST v1.1 in the subgroup of 41 patients with measurable brain metastases at baseline.7
64% of responders achieved an intracranial response duration ≥24 monthsb with ALUNBRIG vs NE for crizotinib.7
Brain metastases population (post hoc subgroup from final analysis with 40.4 months of median follow-up)
57% Reduction in the Risk of Death vs Crizotinib8
Interested in learning about the efficacy results of ALUNBRIG in previously treated patients?
The most common adverse reactions (≥25%) with ALUNBRIG were7:
- Diarrhea
- Fatigue
- Nausea
- Rash
- Cough
- Myalgia
- Headache
- Hypertension
- Vomiting
- Dyspnea
aPatients with brain metastases ≥10 mm in longest diameter at baseline.7
bDuration of intracranial response was measured from date of first intracranial response until intracranial disease progression (new lesions, intracranial target lesion diameter growth ≥20% from nadir, or unequivocal progression of intracranial nontarget lesions) or death.7
Long-Term Tolerability Results
ALUNBRIG Demonstrated Long-Term Tolerabilitya in ALTA 1L7
Median duration of treatment with ALUNBRIG: 24.3 months
Median duration of dose intensity with ALUNBRIG: 97%
Dose reductions occurred in 38% of patients receiving ALUNBRIG.7
- The most common adverse reactions in ALTA 1L that led to dose reduction were increased creatine phosphokinase (15%), increased lipase (6.6%), increased amylase (4.4%), increased aspartate aminotransferase (2.2%), ILD/pneumonitis (2.2%), and hypertension (2.2%).7
Permanent discontinuation due to adverse reactions occurred in 13% of patients receiving ALUNBRIG.7
- The most frequent adverse reactions in ALTA 1L that led to discontinuation were ILD/pneumonitis (3.7%) and pneumonia (2.2%).7
Review the well-established safety profile of ALUNBRIG
aBased on the median follow-up in the ALUNBRIG arm of ALTA 1L of 40.4 months.8
One Tablet, Once-a-Day Dosing
To Assist Patients with ALK+ mNSCLC who are Starting ALUNBRIG, the First-month Supply of the Recommended Dosage is Available in an Initiation Pack
ALUNBRIG recommended dosing7
- Take 90 mg of ALUNBRIG orally once daily for the first 7 days
- Then after 7 days, take 180 mg of ALUNBRIG orally once daily
ALUNBRIG is available in 180-mg, 90-mg, and 30-mg tablets.7
Explore more on dosing for ALUNBRIG
1L, first line; ALK, anaplastic lymphoma kinase; ALK+, ALK-positive; CI, confidence interval; HR, hazard ratio; ITT, intention to treat; mNSCLC, metastatic non-small cell lung cancer; NE, not estimable; OS, overall survival; PFS, progression-free survival.
Dr Mohammad Jahanzeb is a paid consultant for Takeda.