2019 ASCO Annual Meeting!
Session: Melanoma/Skin Cancers
Type: Oral Abstract Session
Time: Tuesday June 4, 9:45 AM to 12:45 PM
Pathological response and survival with neoadjuvant therapy in melanoma: A pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 9503)
Author(s): Alexander M. Menzies, Elisa A. Rozeman, Rodabe Navroze Amaria, Alexander Chan Chi Huang, Richard A. Scolyer, Michael T. Tetzlaff, Bart A. Van De Wiel, Serigne Lo, Ahmad A. Tarhini, Hussein Abdul-Hassan Tawbi, Elizabeth M. Burton, Giorgos Karakousis, Paolo Antonio Ascierto, Andrew Spillane, Michael A. Davies, Alexander Christopher Jonathan Van Akkooi, Tara C. Mitchell, Georgina V. Long, Jennifer Ann Wargo, Christian U. Blank, International Neoadjuvant Melanoma Consortium (INMC); Melanoma Institute Australia, University of Sydney, Royal North Shore Hospital, Sydney, Australia; Netherlands Cancer Institute, Amsterdam, Netherlands; The University of Texas - MD Anderson Cancer Center, Houston, TX; Univ of Pennsylvania, Bryn Mawr, PA; The University of Sydney, Melanoma Institute Australia and Royal Prince Alfred Hospital, Sydney, NSW, Australia; The University of Texas MD Anderson Cancer Center, Houston, TX; Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Case Comprehensive Cancer Center/Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; Istituto Nazionale dei Tumori IRCCS Fondazione, Naples, Italy; Melanoma Institute Australia, Sydney, Australia; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, Australia
Background: Pathological complete response (pCR) to neoadjuvant systemic therapy (NST) correlates with survival, and is recognized as a path to regulatory approval in several cancers. Recent trials have reported that neoadjuvant immunotherapy (IT) and targeted therapy (TT) regimens achieve high pCR rates and impressive recurrence-free survival in stage III melanoma, however, the relationship between pCR, relapse-free (RFS) and overall survival (OS) in larger datasets of melanoma patients (pts) remains unknown. Methods: We pooled data from 6 modern NST clinical trials of anti-PD-1 based immunotherapy or BRAF/MEK targeted therapy conducted across institutions participating in the INMC. Pts with RECIST measurable, surgically resectable clinical stage III melanoma who underwent surgery were included. NST regimens included nivolumab (as monotherapy or in combination with ipilimumab), pembrolizumab or dabrafenib+trametinib. Baseline disease characteristics, treatment regimen, pCR and RFS were examined. Results: 184 pts with clinical stage III melanoma (AJCCv7: 100 IIIB, 84 IIIC) completed NST (133 IT, 51 TT) and underwent surgery. Median age was 57y (range 18-87). A pCR was observed in 41% of patients; 51 (38%) with IT and 24 (47%) with TT. Median follow-up post-surgery is 13 mo (95% CI 12-16); 10 mo with IT and 22 mo with TT. 44 (24%) pts have recurred (17 loco-regional, 21 distant, 6 both sites at first recurrence), 18 (14%) after IT and 26 (51%) after TT. 12-month RFS was improved with IT vs TT (83% vs 65%, p < 0.001). For those with pCR, 7% have recurred, 0/51 (0%) after IT, 7/17 (41%) after TT. For those without pCR, 34% have recurred, 18/82 (22%) after IT and 19/27 (70%) after TT. 12-month RFS was improved in those with pCR vs without pCR (95% vs 62%, p < 0.001), including in those with IT (100% vs 72%, p < 0.001) and TT (88% vs 43%, p < 0.001). 16 (9%) patients have died including two who had a pCR, both from TT. Conclusions: Neoadjuvant IT and TT are active regimens in resectable clinical stage III melanoma patients and are associated with high pCR rate. The ability to achieve pCR correlates with improved RFS and remarkably no patient with pCR from immunotherapy has recurred to date.
2. Association between baseline disease characteristics and relapse-free survival (RFS) in patients (pts) with BRAF V600-mutant resected stage III melanoma treated with adjuvant dabrafenib (D) + trametinib (T) or placebo (PBO).