Abstract 1114P
Background
Preclinical data suggest that BRAF inhibition provides a more favorable immune microenvironment for subsequent response to immunotherapy. We aimed to evaluate the efficacy and safety of combining vemurafenib (BRAF inhibitor) with a programmed death 1 (PD-1) inhibitor in patients with BRAF V600-mutant melanoma in China.
Methods
Advanced BRAF V600-mutant melanoma patients treated with vemurafenib and anti-PD-1 antibody at Sun-Yat Sen University Cancer Center between June 2017 and May 2019 were retrospectively analyzed. Vemurafenib was administered with a 4–6-weeks run-in period followed by PD-1 blockade (pembrolizumab or toripalimab) combined with vemurafenib until disease progression or unacceptable toxicity. Response was assessed by the Response Evaluation Criteria in Solid Tumors version 1.1.
Results
In total, 39 patients were included. All the patients had tumor shrinkage. The objective response rate was 64.1% (95% CI, 48.7–79.4) and the complete response was observed in 8 (20.5%; 95% CI, 7.7–33.3) patients. The median progression-free survival (PFS) was 13.2 months (95% CI: 8.2–18.2). The median duration of response (DOR), and overall survival (OS) were not reached after a median follow-up of 12.1 months. The response was ongoing in 16 (41%) patients. The estimated 1-year survival rate was 86.7%. During the combination therapy, treatment-related adverse events (TRAEs) of any grade occurred in 36 (92.3%) patients. Eleven patients (28.2%) experienced grade 3/4 TRAEs, 10 presented with rash and 1 with elevated transaminase. TRAEs led to discontinuation of ≥1 study drug in seven (17.9%) patients. Programmed death ligand 1 expression on the tumor cell and tumor mutation burden at baseline did not correlate with response rate and survival time. Table: 1114P
| Characteristic | No. of patients (%), n=39 |
| Age, years | 51 (24–77) |
| Male | 26 (66.7) |
| ECOG | |
| 0 | 22 (56.7) |
| 1 | 17 (43.6) |
| Clinical subtype of primary tumor | |
| Acral | 2 (5.1) |
| CSD | 11 (28.2) |
| Non-CSD | 19 (48.7) |
| Unknown | 7 (17.9) |
| Brain metastases | |
| Yes | 6 (15.4) |
| No | 33 (84.6) |
| Liver metastases | |
| Yes | 11 (28.2) |
| No | 28 (71.8) |
| Metastatic organs | |
| >2 | 17 (43.6) |
| ≤2 | 22 (56.4) |
| LDH | |
| ≤UNL | 30 (76.9) |
| ＞UNL | 9 (23.1) |
| Prior systemic therapy | |
| No | 29 (74.4) |
| Yes | 10 (25.6) |
Conclusions
Vemurafenib combined with anti-PD-1 antibody had promising clinical activity and manageable safety. Toxicity, especially rash, is more common for this combination than for either agent alone.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.