Popat 2019.
| Study name | Brigatinib versus crizotinib in ALK‐positive non‐small‐cell lung cancer |
| Methods |
Study design: randomised controlled trial Study grouping: parallel group |
| Participants |
Baseline characteristics Brigatinib 7‐day lead in 90 mg orally, daily, then 180 mg orally, daily, continuously
Alectinib 600 mg orally, twice daily, continuously
Inclusion criteria Have ECOG PS of 0 to 2. Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent) or stage IV NSCLC. Must meet 1 of the following criteria: have documentation of ALK rearrangement by a positive result from the Vysis ALK Break‐Apart fluorescence in situ hybridisation (FISH) Probe Kit or the Ventana ALK (D5F3) CDx Assay or Foundation Medicine's FoundationOne CDx. Have documented ALK rearrangement by a different test and be able to provide tumour sample to the central laboratory. (NOTE: central laboratory ALK rearrangement testing results are not required to be obtained before randomisation). Had progressive disease whilst on crizotinib, as assessed by the investigator or treating physician. (NOTE: crizotinib does not need to be the last therapy a participant received. The participant may have received chemotherapy as his/her last therapy). Treatment with crizotinib for at least 4 weeks before progression. Have had no other ALK inhibitor other than crizotinib. Have had no more than 2 prior regimens of systemic anticancer therapy (other than crizotinib) in the locally advanced or metastatic setting. NOTE: a systemic anticancer therapy regimen will be counted if it is administered for at least 1 complete cycle. A new anticancer agent used as maintenance therapy will be counted as a new regimen. Neoadjuvant or adjuvant systemic anticancer therapy will be counted as a prior regimen if disease progression/recurrence occurred within 12 months upon completion of this neoadjuvant or adjuvant therapy. (Systemic therapy followed by maintenance therapy will be considered as 1 regimen if the maintenance therapy consists of a drug or drugs that were used in the regimen that immediately preceded maintenance.) Have at least 1 measurable (i.e. target) lesion per RECIST v1.1. Have recovered from toxicities related to prior anticancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 Grade <= 1. (NOTE: treatment‐related alopecia or peripheral neuropathy that are Grade > 1 are allowed, if deemed irreversible). Have adequate organ function, as determined by the following:
Suitable venous access for study‐required blood sampling (i.e. including pharmacokinetic and laboratory safety tests) Exclusion criteria Had participated in the control (crizotinib) arm of Study AP26113‐13‐301 (ALTA 1L). Had received crizotinib within 7 days of randomisation. Have a history or presence at baseline of pulmonary interstitial disease, drug‐related pneumonitis, or radiation pneumonitis. Have uncontrolled hypertension. Patients with hypertension should be under treatment for control of blood pressure upon study entry. Had received systemic treatment with strong cytochrome P‐450 (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, or moderate CYP3A inducers within 14 days before randomisation. Treatment with any investigational systemic anticancer agents within 14 days or 5 half‐lives, whichever is longer, before randomisation. Had received chemotherapy or radiation therapy within 14 days of randomisation except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy. Had received antineoplastic monoclonal antibodies within 30 days of randomisation. Had major surgery within 30 days of randomisation. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening (patients with asymptomatic brain metastases or those who have stable symptoms and did not require an increased dose of corticosteroids to control symptoms within 7 days before randomisation will be enrolled). NOTE: If a patient has worsening neurological symptoms or signs due to CNS metastasis, the patient needs to complete local therapy and be neurologically stable (with no requirement for an increasing dose of corticosteroids or use of anticonvulsants) for 7 days before randomisation. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed. Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to, the following: myocardial infarction within 6 months before randomisation. Unstable angina within 6 months before randomisation. New York Heart Association class III or IV heart failure within 6 months before randomisation. History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician. Any history of clinically significant ventricular arrhythmia. Had cerebrovascular accident or transient ischaemic attack within 6 months before first dose of study drug. Have malabsorption syndrome or other gastrointestinal illness or condition that could affect oral absorption of the study drug. Have an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics. Have a known history of HIV infection. Testing is not required in the absence of history. Known hepatitis B surface antigen‐positive, or known or suspected active hepatitis C infection. Have a known or suspected hypersensitivity to brigatinib or alectinib or their excipients. Life‐threatening illness unrelated to cancer |
| Interventions |
Intervention Characteristics Brigatinib 7‐day lead in 90 mg orally, daily, then 180 mg orally, daily, continuously
Alectinib 600 mg orally, twice daily, continuously
|
| Outcomes | Progression‐free survival (PFS) as assessed by blinded independent review committee (BIRC) per RECIST v1.1 [ Time Frame: up to 5 years ] Time to intracranial progression (iPD) as assessed by BIRC per modified RECIST v1.1 [ Time Frame: up to 5 years ] Overall survival (OS) [ Time Frame: up to 5 years ] Objective response rate (ORR) as assessed by investigator and BIRC per RECIST v1.1 [ Time Frame: up to 5 years ] Time to response as assessed by investigator and BIRC [ Time Frame: up to 5 years ] Duration of response (DOR) as assessed by BIRC [ Time Frame: up to 5 years ] Intracranial objective response rate (iORR) as assessed by BIRC per modified RECIST v1.1 [ Time Frame: up to 5 years ] Intracranial duration of response (iDOR) as assessed by the BIRC per modified RECIST v1.1 [ Time Frame: up to 5 years] Health‐related quality of life (HRQoL) from EORTC QLQ‐C30 v3.0 score [ Time Frame: first dose of study drug up to 30 days after last dose (approximately 9 years) ] |
| Starting date | May 2016 |
| Contact information | |
| Notes | pubmed.ncbi.nlm.nih.gov/30280657/ |
CNS: central nervous system ECOG PS: Eastern Cooperative Oncology Group Performance Status EORTC QLQ‐BN20: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Brain Cancer Module EORTC QLQ‐C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core EORTC QLQ‐LC13: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Lung Cancer Module NSCLC: non‐small cell lung cancer RECIST: Response Evaluation Criteria in Solid Tumours TKI: tyrosine kinase inhibitor