Abstract 1108P
Background
Initial treatment decision-making for BRAF+ Metastatic Melanoma (MM) patients remains complex. TT with BRAF-MEK inhibition is associated with high ORR but are thought to be of limited duration, while checkpoint inhibitors (IO) are associated with lower ORR but can be more durable. In absence of head-to-head clinical trial data, it is unclear which treatment sequence (1L IO to 2L TT vs 1L TT to 2L IO) provides maximum benefit to patients. This study compares outcomes in the RW across the two treatment sequences.
Methods
The study included BRAF+ MM patients (n=358) who received both 1L and 2L therapies (IO and TT) according to the NCCN guidelines from Jan 1, 2014 up to Dec 31, 2018. Data was obtained from academic and community sites in the US using a RW registry (NOBLE study). Patient characteristics were analyzed descriptively. Kaplan-Meier curves and Cox regression model were used to compare progression free survival (PFS) and 2-year overall survival (OS) across the two treatment sequences. Differences in patient characteristics including disease severity across the two sequences were adjusted using inverse probability of treatment weighting (IPTW).
Results
Patients who received the TT to IO sequence vs IO to TT sequence were more likely to have elevated LDH (30.2% vs 17.7%) and 3+ organ sites of metastasis (47.4% vs 36.5%). Regardless of treatment sequence, patients progressed relatively rapidly through both 1L and 2L therapies (combined PFS of 13.2m for TT-IO and 12m for IO-TT). The 2-year OS was 76% for the TT-IO sequence compared to 77% for IO-TT. Adjusted Cox regression model found no statistical difference in outcomes across the two sequences.
Conclusions
RW data suggests that half of BRAF+ MM patients, regardless of initial treatment choice, are likely to progress through both 1L and 2L treatments within 12 months. Pending the results of randomized clinical trials, this RW study found no difference in outcomes across treatment sequences. BRAF+ MM patients may require more intensive, alternative approaches than the current sequential TT/IO approach, as outcomes in clinical practice are suboptimal.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Novartis.
Funding
Novartis.
Disclosure
A. Betof Warner: Honoraria (self): Nanobiotix, Inc; Honoraria (self): LG Chem Life Sciences, Inc; Honoraria (self): Iovance, Inc. A.A. Tarhini: Advisory/Consultancy: Novartis; Advisory/Consultancy: Genentech-Roche; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Partner Therapeutics; Research grant/Funding (self), Contracted Research: OncoSec; Research grant/Funding (self), Contracted Research: Clinigen. B. Kang, A. Nakasato M. Vance, Y-L. Ling, J. Pate: Full/Part-time employment: Novartis. J. Tang: Research grant/Funding (self): Novartis. All other authors have declared no conflicts of interest.