Abstract
9062 Background: Accelerated tumor growth has been demonstrated on BRAFi cessation in BRAFi-resistant melanoma cell lines. In BRAFi-treated pts initial response rates are high but most have PD at 6+ months. The benefit of ongoing BRAFi after PD is unknown. We sought to describe the characteristics of pts treated beyond progression (TBP) vs those not TBP, and whether TBP prolongs survival. Methods: Clinicopathologic data were collected on 112 pts enrolled in phase I-IV clinical trials at Westmead Hospital and Melanoma Institute Australia from July 2009 to Sept 2012 with unresectable stage IIIC or IV BRAF+ melanoma treated with single agent dabrafenib or vemurafenib. TBP was defined as ongoing BRAFi >28 days beyond RECIST PD. Pt and disease characteristics at baseline and at PD were examined, as well as survival data. Results: 92/112 (82%) pts had RECIST PD. 36/92 (39%) pts were TBP (mean 144 days, median 93 days, range 29–572 days). Pts TBP were significantly more likely to have achieved a RECIST response (CR/PR) prior to PD, have a lower ECOG at PD, presence of brain metastases at PD, have PD treated locally and a smaller RECIST sum of diameters (SoD) at PD, compared with those not TBP (all p<0.05). Median OS from commencement of BRAFi in those TBP was longer than those not TBP (15.0 vs 6.5 months, p<0.001), as was OS from RECIST PD (7.4 vs 1.9 mo, p=0.001). In multivariate analysis of all pts, TBP improved OS from RECIST PD (HR 0.32, p=0.012) even after adjusting for other potential prognostic factors at PD (see table). Within the TBP cohort, RECIST SoD at PD was the only factor that influenced OS from PD (p=0.009), and presence of brain metastases did not. Conclusions: Treatment with BRAFi may be continued after RECIST PD in selected pts, and is associated with a prolonged OS compared with ceasing treatment at PD. [Table: see text]
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