Abstract 422: Sequential targeted therapy and immunotherapy of a BRAF positive metastatic melanoma patient with BRAF inhibitor vemurafenib, MEK inhibitor cobimetnib and a novel PD-1 antibody Sintilimab
Authors: Zhang Yu , Li Xiaomo , Ma Tonghui , Cao Baoshan 
Published: July 2021

Abstract
Targeted therapy has dramatically improved the outcome of BRAF mutated melanoma patients. However, its response is usually brisk and lacks the durability of immunotherapy. Decisions about targeted therapy alone, immunotherapy alone, targeted therapy/immunotherapy combination or immunotherapy after targeted therapy require an oncologist to comprehensively evaluate multiple clinical factors. Here we report the sequential treatment of a BRAF positive metastatic melanoma patient with non-standard regimes due to practical reasons. A 75-year old male patient presented a black cauliflower-like mass on back and bilateral axillary lymph nodes enlargement. Postoperative pathologic examination confirmed a nodular malignant melanoma of 1.6 cm in diameter and 0.7 cm thick. NGS sequencing of the tumor revealed the canonical BRAF V600E mutation. As vemurafenib was the only approved melanoma targeted therapy drug in China at the time of diagnosis, it was administered (960 mg bid) as first-line therapy since September 2019 and the patient's response was confirmed by the significant reduction and softening of the left axillary node. One month later the node rapidly enlarged to 15 cm, and the blood scab fell off followed by pulsatile massive hemorrhage (~1000 mL). We performed an emergent angiograph and a transarterial embolization (TAE), aimed at selectively occluding the tumor artery by using gelatin sponge particle and coils. The hemorrhage was significantly reduced after TAE therapy and a left axillary residual cavity was formed. When the patient presented a progression of lymph node metastases, BRAF/MEK inhibitor combination was selected as the second-line therapy from December 2019. He received vemurafenib at a dose of 480 mg bid combined with cobimetinib 60mg qd (3 consecutive weeks every 28 days), the treatment was ongoing till disease progression in April 2020. Immunohistochemical analysis of the biopsy specimen demonstrated PD-L1 expression in 4% of tumor cells and immunotherapy was chosen as the third-line therapy. Sintilimab, a PD-1 antibody approved in China for the treatment of classical Hodgkin lymphoma, is undergoing clincial trials for multiple solid tumors including melanoma. Given the high cost of immunotherapy and the fact that Sintilimab is the only PD-1 inhibitor included in China's National Reimbursement Drug List, the patient started off-label use of Sintilimab and achieved partial response. In summary, our patient had an unconventional timeline of multiple therapies including surgery, TAE, targeted therapy and immunotherapy. His case demonstrated that meaningful clinical responses can be achieved with sequential targeted therapy/immunotherapy in BRAF-mutated metastatic melanoma and the novel PD-1 antibody Sintilimab is worth further investigation for its efficacy in metastatic melanoma.
Citation Format: Yu Zhang, Xiaomo Li, Tonghui Ma, Baoshan Cao. Sequential targeted therapy and immunotherapy of a BRAF positive metastatic melanoma patient with BRAF inhibitor vemurafenib, MEK inhibitor cobimetnib and a novel PD-1 antibody Sintilimab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 422.