PMID- 32447656 OWN - NLM STAT- MEDLINE DCOM- 20210427 LR - 20210427 IS - 1534-4681 (Electronic) IS - 1068-9265 (Linking) VI - 27 IP - 13 DP - 2020 Dec TI - Adjuvant Therapy Failure Patterns in the Modern Era of Melanoma Management. PG - 5128-5136 LID - 10.1245/s10434-020-08631-2 [doi] AB - BACKGROUND: The management of patients with resected stage 3 melanoma has changed significantly due to adoption of the Multicenter Selective Lymphadenectomy Trial (MSLT)-2 guidelines and to the survival benefit of adjuvant anti-PD-1 immunotherapy and BRAF/MEK-inhibitor (BRAF/MEKi) therapy. Data are scarce regarding recurrence patterns, adjuvant therapy responses, and therapy-associated adverse events (AEs) in the modern era. METHODS: This single-institution, retrospective study analyzed surgically resected stage 3 and oligometastatic stage 4 patients who received anti-PD-1, BRAF/MEKi, or surgery with active surveillance only. The primary end point of the study was recurrence-free survival (RFS). The secondary end points were the location and clinical characteristics of recurrence and therapy-associated AEs. RESULTS: From a cohort of 137 patients, the study enrolled 102 patients treated with adjuvant anti-PD-1 (n = 46), adjuvant BRAF/MEKi (n = 3), or surgery alone (n = 26). During a mean follow-up period of 17 months, 20% of the ani-PD-1 patients, 13% of the BRAF/MEKi patients, and 42% of the surgery-only patients experienced recurrence. Log-rank testing showed a significantly longer RFS for the patients treated with anti-PD-1 [15.3 months; interquartile range (IQR), 8.2-23.2 months; p = 0.04] or BRAF/MEKi (17.9 months; IQR, 12.5-23 months; p = 0.01) than for those treated with surgery alone (11.9 months; IQR, 7.0-17.6 months). In the anti-PD-1 group, AEs occurred less frequently than in the BRAF/MEKi group (54% vs 80%; p = 0.03). CONCLUSIONS: Adjuvant anti-PD-1 and BRAF/MEKi were associated with significantly improved RFS for the patients with resected stage 3 or 4 melanoma. The BRAF/MEKi group had significantly more AEs than the anti-PD-1 group. This is the first study to characterize real-world recurrence in the modern era of adjuvant therapy for melanoma. FAU - Rauwerdink, Daan Jan Willem AU - Rauwerdink DJW AD - Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. FAU - Molina, George AU - Molina G AD - Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. FAU - Frederick, Dennie Tompers AU - Frederick DT AD - Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. FAU - Sharova, Tanya AU - Sharova T AD - Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. FAU - Carmichael, Harrison AU - Carmichael H AD - Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. FAU - Boland, Genevieve Marie AU - Boland GM AD - Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. gmboland@partners.org. AD - Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Yawkey Center for Outpatient Care, 32 Fruit Street, Boston, MA, 02114, USA. gmboland@partners.org. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20200523 PL - United States TA - Ann Surg Oncol JT - Annals of surgical oncology JID - 9420840 RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) SB - IM MH - Humans MH - *Melanoma/drug therapy MH - Neoplasm Recurrence, Local/drug therapy MH - Protein Kinase Inhibitors MH - Proto-Oncogene Proteins B-raf/genetics MH - Retrospective Studies MH - *Skin Neoplasms/drug therapy EDAT- 2020/05/25 06:00 MHDA- 2021/04/28 06:00 CRDT- 2020/05/25 06:00 PHST- 2020/02/25 00:00 [received] PHST- 2020/05/25 06:00 [pubmed] PHST- 2021/04/28 06:00 [medline] PHST- 2020/05/25 06:00 [entrez] AID - 10.1245/s10434-020-08631-2 [pii] AID - 10.1245/s10434-020-08631-2 [doi] PST - ppublish SO - Ann Surg Oncol. 2020 Dec;27(13):5128-5136. doi: 10.1245/s10434-020-08631-2. Epub 2020 May 23.