An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer. (2nd December 2018)

• Record Type: Journal Article
• Authors: Liede, Alexander; Hernandez, Rohini K.; Wade, Sally W.; Bo, Ronghai; Nussbaum, Nathan C.; Ahern, Elizabeth; Dougall, William C.; Smyth, Mark J.
• Is Part Of: Oncoimmunology. Volume 7:Number 12(2018)
• Publication Date: 2018-12-02
• Subjects: Immune checkpoint inhibitor -- melanoma -- non-small cell lung cancer -- RANK-ligand inhibitor -- denosumab -- real-world -- response -- survival; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1480301
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: After a case report of profound clinical response in a melanoma patient following treatment with an immune checkpoint inhibitor (ICI) and RANK-ligand inhibitor denosumab, we identified similar patients from electronic health records (EHR) and described patient characteristics and outcomes. This 2017 observational study used Flatiron Health's EHR database from ~255 US cancer clinics. Included were advanced melanoma or non-small-cell lung cancer (NSCLC) patients who received denosumab within 30 days of CTLA-4 (ipilimumab) or PD1 (pembrolizumab, nivolumab) inhibitors start with a minimum of 6 months of follow up. Real-world tumor response (rwTR) was analyzed for scans available up to 30 days after concomitant therapy. Preclinical experiments evaluated sequencing of ICI, denosumab vs monotherapy or control. Melanoma (n = 66) patients received concomitant denosumab/ICI for a mean 4.0 months, 3.1 months for NSCLC (n = 241). Two-thirds of patients had best rwTR evaluable (complete [CR], partial response [PR], stable disease [SD], or disease progression [PD]). Longer mean duration of concomitant exposure was associated with overall response rate (ORR; CR+PR) in melanoma (p = 0.0172), NSCLC (p < .0001), and combined cohorts (p < .0001). The disease control rate (ORR plus SD) was 56% amongst melanoma patients and 58% amongst NSCLC patients. Longer concomitant therapy was associated with increased overall survival, primarily in NSCLC (p < .0001). Preclinical data suggest that ICI initiated before or at same time as denosumab was optimal. Results provide proof-of-concept that rwTR is associated with concomitant denosumab/ICI. Crude survival analyses supported the association of concomitant therapy and improved outcomes outside of clinical trials and warrant comparative study.