Alessio Cortellini, Douglas B. Johnson, Amin Nassar, Sebastiano Buti, Pamela Pizzutilo, Fei Ye, Shravanti Macherla, David J. Pinato, Asrar Alahmadi, Giuseppe Lamberti, Anwaar Saeed, Ella Daniels, Paolo A. Ascierto, Carolyn J Presley, Sarah Abou Alaiwi, Melissa Bersanelli, Maluki Radford, Foteini Kalofonou, Tamara A. Sussman, Akiva Diamond, Maria Giovanna Dal Bello, Christopher J. Hoimes, Paolo Marchetti, Domenico Mallardo, Weijie Ma, Rebecca Irlmeier, Teja Ganta, Raffaele Giusti, Andrea Botticelli, Neha Debnath, Caroline A. Nebhan, Carlo Genova, Toni K. Choueiri, Biagio Ricciuti, Abdul Rafeh Naqash, Nikhil H. Ramaiya, Annamaria Catino, Haocan Song, Vito Vanella, Marco Filetti, Yinghong Wang, Thomas U. Marron, Chiara Casartelli, Dwight H. Owen, and Domenico Galetta
BackgroundImmune checkpoint inhibitors (ICIs) are approved by the U.S. Food&Drug Administration in over 17 tumor types. Older adult patients make up about a quarter of all cancer patients but are historically understudied in cancer clinical trials. ICIs are associated with immune-related adverse events (irAEs), which may be particularly morbid for older adult patients with underlying comorbidities and impaired functional status. In this study, we provide insight into the real-world safety and efficacy of ICIs among older adult patients (≥80 years) with cancer.MethodsThis is a multicenter, international retrospective study of tumor-agnostic older adult patients with cancer treated with single-agent ICIs between 2010–2019 from 18 academic centers in the U.S. and Europe. A cohort of 928 patients aged ≥80 years during treatment with ICI was assembled and analyzed to evaluate clinical outcomes and irAE patterns in older adult patients treated with single-agent ICIs.ResultsMedian age at ICI initiation was 83.0 years (range 75.8–97.0). Most patients (86.9%) were treated with anti-PD-1 therapy. Among the full cohort, the three most common tumors were non-small cell lung cancer (NSCLC, 37.2%,n=345), melanoma (35.5%,n=329), and genitourinary (GU) tumors (16.5%,n=153). Objective response rates for patients with NSCLC, melanoma, and GU tumors were 32.2%, 39.3%, and 26.2%, respectively. Median progression-free survival (PFS) was 6.7 months (95%CI, 5.2–8.6) for patients with NSCLC, 11.1 months (95%CI, 8.9–16.0) for patients with melanoma, and 6.0 months (95% CI, 5.0–10.7) for patients with GU malignancy. Median overall survival (OS) was 10.9 months (95%CI, 8.6–13.1) for patients with NSCLC, 30.0 months (95%CI, 23.6–46.4) for patients with melanoma, and 15.0 months (95%CI 9.1–25.4) for GU patients (Figure 1A-C). Within histology-specific cohorts (NSCLC, melanoma and GU), clinical outcomes were similar across age subgroups (90). Among all patients (N=928), 41.3% experienced ≥1 irAE(s), including 12.2% reported to be grade (G)3–4. No irAE-related deaths occurred. The median time to irAE onset was 9.8 weeks; 57% occurred within the first 3 months after ICI initiation. ICI was discontinued due to irAEs in 16.1% patients. There was no significant difference in the rate of irAEs among patients age ConclusionsICIs are effective and generally well-tolerated among older patients with cancer. However, ICI discontinuation due to irAE is more frequent with increasing age.