Daan Jan Willem Rauwerdink1, George Molina1, Dennie Tompers Frederick1, Tanya Sharova1, Harrison Carmichael1, Genevieve Marie Boland2,3. 1. Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. 2. Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. gmboland@partners.org. 3. 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.
Abstract
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.
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-1patients, 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.
Authors: Axel Hauschild; Reinhard Dummer; Dirk Schadendorf; Mario Santinami; Victoria Atkinson; Mario Mandalà; Vanna Chiarion-Sileni; James Larkin; Marta Nyakas; Caroline Dutriaux; Andrew Haydon; Caroline Robert; Laurent Mortier; Jacob Schachter; Thierry Lesimple; Ruth Plummer; Kohinoor Dasgupta; Tomas Haas; Mark Shilkrut; Eduard Gasal; Richard Kefford; John M Kirkwood; Georgina V Long Journal: J Clin Oncol Date: 2018-10-22 Impact factor: 44.544
Authors: Kristy K Broman; Tasha M Hughes; Lesly A Dossett; James Sun; Michael J Carr; Dennis A Kirichenko; Avinash Sharma; Edmund K Bartlett; Amanda Ag Nijhuis; John F Thompson; Tina J Hieken; Lisa Kottschade; Jennifer Downs; David E Gyorki; Emma Stahlie; Alexander van Akkooi; David W Ollila; Jill Frank; Yun Song; Giorgos Karakousis; Marc Moncrieff; Jenny Nobes; John Vetto; Dale Han; Jeffrey Farma; Jeremiah L Deneve; Martin D Fleming; Matthew Perez; Kirsten Baecher; Michael Lowe; Roger Olofsson Bagge; Jan Mattsson; Ann Y Lee; Russell S Berman; Harvey Chai; Hidde M Kroon; Roland M Teras; Juri Teras; Norma E Farrow; Georgia M Beasley; Jane Yc Hui; Lukas Been; Schelto Kruijff; David Boulware; Amod A Sarnaik; Vernon K Sondak; Jonathan S Zager Journal: J Am Coll Surg Date: 2020-12-13 Impact factor: 6.532
Authors: Kristy K Broman; Deepti Bettampadi; Jaileene Pérez-Morales; James Sun; Dennis Kirichenko; Michael J Carr; Zeynep Eroglu; Ahmad A Tarhini; Nikhil Khushalani; Matthew B Schabath; Amod Sarnaik; Vernon K Sondak; Jonathan S Zager Journal: Ann Surg Oncol Date: 2021-08-06 Impact factor: 5.344