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219 Long-term clinical outcomes associated with sequential treatment of BRAF mutant advanced melanoma patients
  1. Ahmad Tarhini1,
  2. David McDermott2,
  3. Apoorva Ambavane3,
  4. Agnes Benedict3,
  5. Cho-Han Lee4,
  6. Corey Ritchings4,
  7. Brian Stwalley4,
  8. Meredith Regan5 and
  9. Michael Atkins6
  1. 1Moffitt Comprehensive Cancer Center and Research Institute, Tampa, FL, USA
  2. 2Harvard Medical School; Beth Israel Deaconess Medical Center, Boston, MA, USA
  3. 3Evidera, London, MD, UK
  4. 4Bristol Myers Squibb, Princeton, NJ, USA
  5. 5Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA, USA
  6. 6Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA


Background Patients with BRAF mutant advanced melanoma can be treated sequentially with immunotherapies (IO) and BRAF+MEK inhibitors. We evaluated the clinical outcomes associated with various treatment sequences for BRAF mutant advanced melanoma based on the 5-year follow-up data from clinical trials.

Methods In the absence of head-to-head trial data, a matching-adjusted indirect comparison (MAIC) was conducted for IO vs. BRAF+MEK inhibitors, using the longest follow-up available in the published literature. Multivariate risk equations were developed to predict time-to-event outcomes based on patient-level data from pooled CheckMate-067 &-069 trials. Risk equations were inserted into a discrete event simulation to estimate the average life-years (LYs) and quality-adjusted life-years (QALYs) that can be gained with various treatment sequences over a lifetime horizon. Treatment sequences and corresponding efficacy data sources are presented below (table 1). Utility weights for quality-adjustment of LYs were obtained from published literature.

Results Treatment sequences starting with IO followed by BRAF+MEK were associated with 2.9–4.3 years of additional survival and 2.2–3.3 years of quality-adjusted survival versus sequences starting with BRAF+MEK followed by anti-PD-1. After 1L IO, the time spent in the treatment-free interval (TFI) is 3.3–5.0 years. LYs, QALYs, and time spent in TFI were higher with sequences starting with anti-PD-1+anti-CTLA-4 vs. anti-PD-1 alone.

Abstract 219 Table 1

Clinical outcomes on treatment sequences for BRAF MT melanoma

Conclusions In this sequencing model with 5-year data from randomized clinical trials, initiating 1L treatment with IO provided prolonged survival compared to initiating 1L treatment with BRAF+MEK. Time spent in TFI represents a significant proportion of survival time for patients on IO initiating sequences. Limitations of the study are the reliance on published information for BRAF+MEK, which could lead to biases due to unmeasured differences in the patient populations or trial conduct and the absence of data on 2L combination IO. Anti-PD-1+anti-CTLA-4 as second line option has not been included because of a lack of clinical evidence. Findings from this analysis will require validation in ongoing prospective randomized clinical trials.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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