Abstract
When assessing the value of innovative medicines Health Authorities are often faced with immature overall survival (OS) data from regulatory clinical trials. The aim of our study was to assess the OS benefits of ribociclib combined with letrozole (RIB+LTZ) for first-line treatment in postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease, using anchored adjusted indirect comparison with more mature data. We performed an anchored indirect comparison using simulated treatment comparison (STC) (PMID:25795232) which relay on regression methods to adjust for potential imbalance in effect modifiers (age, bone metastasis, previous chemotherapy, previous adjuvant endocrine therapy). We combined individual patient data (n=668) from the MONALEESA-2 trial (NCT01958021) with median follow-up of 15 months and aggregate data (n=916) from a phase III study of letrozole (LTZ) versus tamoxifen as first-line therapy of advanced breast cancer (PMID:12775735) with longer follow-up time (32 months). Different accelerated time failure models were tested to assess effect modifiers over OS. The Weibull AFT regression model was assumed not only because of its statistical properties (low AIC value) but also because of the clinical and biological plausibility of the extrapolated share of the survival beyond trial data observation. Indirect comparison with STC suggests a significantly 48% reduction in the risk of death for the use of RIB+LTZ relative to LTZ (HR=0.37; 95%CI: 0.34-0.39). Estimated adjusted median OS was 68 months for RIB+LTZ and 36 months for LTZ. The latter compares well with the observed median OS of 34 months (PMID: 12775735) and the former will only occur with longer follow-up in the MONALEESA-2 trial. Adjusted indirect comparison methods are useful to inform about early adoption of innovation in the absence of mature overall survival data from regulatory clinical trials.
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