PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion.
RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy.
CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.
METHODS: This is an 18-month cluster-randomized, open-label, parallel-arm controlled trial conducted at 14 public hospitals in the Perak state of Malaysia. Patients aged 60 and above, who have at least one medication and one comorbidity are eligible. A stratified-cluster randomization design is employed, with 7 hospitals assigned to the control arm and 7 hospitals assigned to the intervention arm. The MALPIP screening tool will be used in the intervention group to review the medications. If PIM is detected, the pharmacists will discuss with doctors and decide whether to stop or reduce the dose. The primary outcomes of this trial are the total number of medications and number of PIM. The secondary outcomes include fall, emergency department visits, readmissions, quality of life and mortality. Outcomes will be measured during enrolment, discharge, 6, 12, and 18 months.
DISCUSSION: This REVMED trial aims to test the hypothesis that a pharmacist-led deprescribing intervention initiated in the hospital will reduce the total number of medications and PIM 18 months after hospital discharge, reducing fall, emergency department visits, readmissions, mortality and lead to improvement in quality of life. Trial findings will quantify the clinical outcomes associated with reducing medications and PIM for hospitalized older adults with polypharmacy.
TRIAL REGISTRATION NUMBER: This trial was prospectively registered at clinicaltrials.gov (NCT05875623) on the 25th of May 2023. NCT05875623 Clinicaltrials.gov URL: NCT05875623 registered on 25th July 2023.