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Outcomes of patients with malignant melanoma treated with immunotherapy prior to or after vemurafenib.
Session Type and Session Title:
General Poster Session, Melanoma/Skin Cancers
J Clin Oncol 30, 2012 (suppl; abstr 8569)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Treatment of patients (pts) with BRAF mutant malignant melanoma (MM) with vemurafenib (vem), a BRAF inhibitor (BRAFi), is associated with a high response rate (RR) and improvement in progression free survival (PFS) and overall survival (OS) compared to standard chemotherapy. Responses to vem are typically not durable and most pts require additional therapy. However, there is little data to guide sequencing of vem with other standard therapies such as ipilimumab (ipi) or interleukin 2 (IL-2). Methods: 43 pts treated with vem as part of clinical trials from 2009-2012 were retrospectively identified. RR of vem was calculated for all pts as well as for pts treated with immunotherapy (IT) prior to vem. The OS from first systemic and vem treatment, duration of vem therapy, OS from when pts came off vem, and PFS and OS for post-vem ipi was determined using Kaplan-Meier estimates. Results: Of the 43 pts, 11 remain on vem and 32 are off vem (19 deceased) with a median follow up of 19 mo. Pre-vem LDH was elevated in 46% (17/37 evaluable pts). The RR to vem was 52% (22/42 evaluable pts), the median duration of therapy 5.6 months (mo), and the median OS 19.3 mo, similar to results in trials. The median OS from initiation of any treatment was 27 mo. 16 pts received IT (11 IL-2, 4 ipi, 1 IL-2 then ipi) prior to vem with a median OS of 31.2 mo; the RR of vem following IT was 75% (12/16). At time of vem discontinuation 50% of pts (12/24 evaluable) had an elevated LDH, and the median OS of the 32 pts who stopped vem was 4 mo from last vem dose. 10 of these pts then received single-agent ipi; six of whom had an elevated LDH. Five pts died within 3 mo of last vem dose, and all 10 pts had disease progression (PD) at 6 months with a median PFS of 0.7 mo and OS of 2.2 mo. The 3 pts who lived beyond 1 year following vem and then ipi were subsequently treated with a BRAFi following PD on ipi. Conclusions: Response to vem following IT appears similar to that seen in previously untreated pts. Median PFS and OS for pts receiving ipi after discontinuation of vem are poor, possibly due to rapid PD at the time of vem discontinuation. Prolonged OS is primarily seen with resumption of BRAF inhibition. Our data suggests that in appropriately selected pts, IT should be considered prior to BRAFi.