Menzies et al. reported the relationship between pathological response and clinical outcomes in 192 patients with clinical stage III melanoma treated with neoadjuvant immunotherapy or BRAF/MEK targeted therapy. Patients who achieved a pathological complete response (pCR; 40%) had improved 2-year RFS (89%) and OS (95%) compared to those without pCR. Combination immunotherapy (anti-CTLA-4 + anti-PD-1) achieved higher pCR (43%), compared to anti-PD-1 alone (20%), and any degree of pathological response (pCR, near pCR or pPR) correlated with improved RFS (96%) and OS (100%). In the targeted therapy group, only pCR correlated with improved RFS and OS.
Contributed by Shishir Pant
ABSTRACT: The association among pathological response, recurrence-free survival (RFS) and overall survival (OS) with neoadjuvant therapy in melanoma remains unclear. In this study, we pooled data from six clinical trials of anti-PD-1-based immunotherapy or BRAF/MEK targeted therapy. In total, 192 patients were included; 141 received immunotherapy (104, combination of ipilimumab and nivolumab; 37, anti-PD-1 monotherapy), and 51 received targeted therapy. A pathological complete response (pCR) occurred in 40% of patients: 47% with targeted therapy and 33% with immunotherapy (43% combination and 20% monotherapy). pCR correlated with improved RFS (pCR 2-year 89% versus no pCR 50%, P < 0.001) and OS (pCR 2-year OS 95% versus no pCR 83%, P = 0.027). In patients with pCR, near pCR or partial pathological response with immunotherapy, very few relapses were seen (2-year RFS 96%), and, at this writing, no patient has died from melanoma, whereas, even with pCR from targeted therapy, the 2-year RFS was only 79%, and OS was only 91%. Pathological response should be an early surrogate endpoint for clinical trials and a new benchmark for development and approval in melanoma.
Author Info: (1) Melanoma Institute Australia, The University of Sydney, Sydney, Australia. (2) Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. (3) Royal North Shor
Author Info: (1) Melanoma Institute Australia, The University of Sydney, Sydney, Australia. (2) Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. (3) Royal North Shore and Mater Hospitals, Sydney, Australia. (4) University of Texas MD Anderson Cancer Center, Houston, TX, USA. (5) Netherlands Cancer Institute, Amsterdam, The Netherlands. (6) Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. (7) Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA. (8) H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. (9) Royal Prince Alfred Hospital, Sydney, Australia. (10) Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale', Napoli, Italy. (11) Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and New Health Pathology, Sydney, Australia. (12) Melanoma Institute Australia, The University of Sydney, Sydney, Australia. georgina.long@sydney.edu.au. (13) Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. georgina.long@sydney.edu.au. (14) Royal North Shore and Mater Hospitals, Sydney, Australia. georgina.long@sydney.edu.au.
#Contributed equally.
