Lee Joanna, Ahmed Tasnia, Maurichi Andrea, Di Guardo Lorenzo, Stagno Anna M, Warburton Lydia, Taylor Amelia M, Livingstone Elisabeth, Rehman Saba, Khattak Adnan, Kahler Katharina C, Vanella Vito, Atkinson Victoria, Millward Michael, Schadendorf Dirk, Johnson Douglas B, Ascierto Paolo A, Hauschild Axel, Lo Serigne N, Long Georgina V, Menzies Alexander M, Carlino Matteo S
Westmead Hospital, Sydney, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
Eur J Cancer. 2023 Jan;179:87-97. doi: 10.1016/j.ejca.2022.11.009. Epub 2022 Nov 12.
BRAF mutant melanoma treated with BRAF ± MEK inhibitor (targeted therapy) has a high response rate; however, most patients progress (PD). Some patients have durable response, but it is unknown whether treatment can be discontinued in these patients. We describe the recurrence risk, progression patterns, response to subsequent treatment, and survival of patients with advanced melanoma who ceased targeted therapy prior to PD.
Ninety-four patients who ceased targeted therapy without progression were identified retrospectively from 11 centres: 45 were male; 81 V600E; 88 stage IV. Fifty-nine were treated with BRAF + MEK inhibitor, and 35 were treated with BRAF inhibitor alone. Median treatment duration was 29.6 months (range 0.36-77.9). At cessation, 67 were in complete response, 21 in partial response, and 2 stable disease.
After median follow-up from cessation of 42.9 months (range 0.0-88.7), 36 (38%) progressed; median time to progression was 4.7 months (range 0.7-56.9); 30 (83%) were asymptomatic and 7 (19%) had new brain metastases. Progression rates did not differ by best response: 34% for complete response and 43% for partial response (P = 0.65). Treatment duration was strongly associated with risk of progression: Median treatment duration was 18.3 (range 0.85-65.7) months for those who progressed and 34.6 (range 0.36-77.9) months for those who did not (P = 0.0004). Twenty-two received further targeted therapy with 15 (68%) responses.
Risk of progression after cessation of targeted therapy is strongly associated with treatment duration. Response to retreatment with targeted therapy is high.
接受BRAF ± MEK抑制剂（靶向治疗）的BRAF突变型黑色素瘤有较高的缓解率；然而，大多数患者会出现疾病进展（PD）。一些患者有持久缓解，但尚不清楚这些患者是否可以停止治疗。我们描述了在疾病进展前停止靶向治疗的晚期黑色素瘤患者的复发风险、进展模式、对后续治疗的反应及生存情况。
从11个中心回顾性识别出94例未进展而停止靶向治疗的患者：45例为男性；81例为V600E突变；88例为IV期。59例接受BRAF + MEK抑制剂治疗，35例仅接受BRAF抑制剂治疗。中位治疗持续时间为29.6个月（范围0.36 - 77.9个月）。停止治疗时，67例完全缓解，21例部分缓解，2例病情稳定。
自停止治疗起中位随访42.9个月（范围0.0 - 88.7个月）后，36例（38%）出现进展；中位进展时间为4.7个月（范围0.7 - 56.9个月）；30例（83%）无症状，7例（19%）出现新发脑转移。进展率在最佳缓解情况方面无差异：完全缓解者为34%，部分缓解者为43%（P = 0.65）。治疗持续时间与进展风险密切相关：进展者的中位治疗持续时间为18.3个月（范围0.85 - 65.7个月），未进展者为34.6个月（范围0.36 - 77.9个月）（P = 0.0004）。22例接受了进一步的靶向治疗，其中15例（68%）有反应。
靶向治疗停止后的进展风险与治疗持续时间密切相关。靶向治疗再治疗的反应率较高。
