Efficacy and safety of treatment modalities across EGFR selected/unselected populations with non-small cell lung cancer and brain metastases: a systematic review and Bayesian network meta-analysis
A partir d'une revue systématique de la littérature (15 essais randomisés, 1 216 patients), cette méta-analyse évalue l'efficacité, du point de vue de la survie globale et de la survie sans progression, et la toxicité des diverses stratégies thérapeutiques chez des patients atteints d'un cancer du poumon non à petites cellules et présentant des métastases cérébrales, avec ou sans mutations EGFR
Résumé en anglais
Objective : To compare the efficacy and safety of treatment modalities across different populations with non-small cell lung cancer and brain metastases.
Methods : A comprehensive search for randomized controlled trials was conducted in databasesincluding PubMed, Embase, the Cochrane library, the ClinicalTrials.gov, and majorinternational conferences. The main outcomes of interest were progression-free survival,overall survival, and severe adverse events. Bayesian network meta-analytical techniqueswere implemented, to compare treatment modalities based on efficacy and safety profiles.The protocol for this study has been registered in the Prospective Register of SystematicReviews (PROSPERO, CRD42020155330).
Results : 15 randomized controlled trials with a total of 1,216 patients were analyzed. Networkmeta-analysis generated six comparisons both in EGFR positive and EGFR unselectedpopulations. For patients harboring EGFR positive mutations, osimertinib appears tosignificantly increase progression-free survival, compared to 1 st generation EGFR-TKI (HR 0.46, 95%CI 0.38-0.55), 2 nd generation EGFR-TKI (HR: 0.59, 95%CI 0.34-0.99), conventional chemotherapy (HR 0.30,95%CI 0.14-0.66), radiotherapy (HR 0.20, 95%CI 0.14-0.29), and radiotherapy plus 1 st generation TKI (HR 0.21, 95%CI 0.14-0.32). Osimertinib also appears to increase thelikelihood of survival and prolong overall survival. For EGFR unselected patients,combined anti-PD1 monoclonal antibody with conventional chemotherapy appears superiorto radiotherapy (HR: 0.20, 95% CI 0.14-0.29), conventional chemotherapy (HR: 0.42,95%CI 0.28-0.68), radiotherapy plus conventional chemotherapy (HR: 0.59, 95%CI 0.32-0.98),radiotherapy plus 1 st generation TKI (HR:0.49, 95%CI 0.25-0.96), and immune checkpoint inhibitors monotherapy(HR:0.44, 95%CI 0.28-0.69). However, combination therapies are generally more toxiccausing an increased number of severe adverse events, particularly when anti-PD1 monoclonalantibody is combined with conventional chemotherapy.
Conclusions : Osimertinib appears to be the most effective and safest treatment in NSCLC patientswith brain metastases, harboring EGFR positive mutations. The anti-PD1 monoclonalantibody and conventional chemotherapy combination increases survival for NSCLC patientswith brain metastases who were not selected according to EGFR mutation, although thisincreased benefit positively correlates with an increased number of severe adverseevents.
