METHODS: This study will include only RCTs published in peer-reviewed journals. A systematic search will be conducted in several electronic databases and other relevant online resources. No limitations are imposed on language or publication date. Participants must be explicitly identified by authors as having OA. Interventions that involved exercise or comparators in any form will be included. Pain is the primary outcome of interest; secondary outcomes will include function and quality of life measures. Quality assessment of studies will be based on the modified Cochrane's risk of bias assessment tool. At least two investigators will be involved throughout all stages of screening and data acquisition. Conflicts will be resolved through discussion. Conventional meta-analysis will be performed based on random effects model and network meta-analysis on a Bayesian model. Subgroup analysis will also be conducted based on study, patient and disease characteristics.
DISCUSSION: This study will provide for the first time comprehensive research evidence for the relative efficacy of different exercise regimens for treatment of OA. We will use network meta-analysis of existing RCT data to answer this question.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033865.
METHODS: In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with EGFR exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivantamab-chemotherapy) or chemotherapy alone. The primary outcome was progression-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy.
RESULTS: A total of 308 patients underwent randomization (153 to receive amivantamab-chemotherapy and 155 to receive chemotherapy alone). Progression-free survival was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio for disease progression or death, 0.40; 95% confidence interval [CI], 0.30 to 0.53; P<0.001). At 18 months, progression-free survival was reported in 31% of the patients in the amivantamab-chemotherapy group and in 3% in the chemotherapy group; a complete or partial response at data cutoff was reported in 73% and 47%, respectively (rate ratio, 1.50; 95% CI, 1.32 to 1.68; P<0.001). In the interim overall survival analysis (33% maturity), the hazard ratio for death for amivantamab-chemotherapy as compared with chemotherapy was 0.67 (95% CI, 0.42 to 1.09; P = 0.11). The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions.
CONCLUSIONS: The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.).