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239 Efficacy and toxicity of single agent immune checkpoint inhibitors among adults with cancer aged ≥80 years: a multicenter international cohort study
  1. Caroline Nebhan1,
  2. Alessio Cortellini2,
  3. Weijie Ma3,
  4. Teja Ganta4,
  5. Haocan Song1,
  6. Fei Ye1,
  7. Rebecca Irlmeier1,
  8. Neha Debnath4,
  9. Anwaar Saeed5,
  10. Maluki Radford5,
  11. Asrar Alahmadi6,
  12. Akiva Diamond6,
  13. Christopher Hoimes7,
  14. Nikhil Ramaiya6,
  15. Carolyn Presley8,
  16. Dwight Owen8,
  17. Sarah Abou Alaiwi9,
  18. Amin Nassar9,
  19. Biagio Ricciuti9,
  20. Giuseppe Lamberti10,
  21. Melissa Bersanelli11,
  22. Chiara Casartelli11,
  23. Sebastiano Buti11,
  24. Paolo Marchetti12,
  25. Raffaele Giusti12,
  26. Marco Filetti1,
  27. Vito Vanella13,
  28. Domenico Mallardo13,
  29. Shravanti Macherla14,
  30. Tamara Sussman15,
  31. Andrea Botticelli16,
  32. Domenico Galetta17,
  33. Annamaria Catino17,
  34. Pamela Pizzutilo17,
  35. Carlo Genova18,
  36. Maria Giovanna Dal Bello19,
  37. Foteini Kalofonou20,
  38. Ella Daniels20,
  39. Paolo Ascierto13,
  40. David Pinato20,
  41. Toni Choueiri9,
  42. Douglas Johnson1,
  43. Thomas Marron4,
  44. Yinghong Wang3 and
  45. Abdul Rafeh Naqash21
  1. 1Vanderbilt University Medical Center, Nashville, TN, USA
  2. 2University of L’Aquila, L’Aquila, Italy
  3. 3MD Anderson Cancer, Houston, TX, USA
  4. 4Icahn School of Medicine at Mount Sinai, New York, USA
  5. 5University of Kansas Cancer Center, Kansas City, KS, USA
  6. 6Case Western Reserve University, Cleveland, USA
  7. 7Duke Cancer Institute, Durham, OH, USA
  8. 8The Ohio State University Comprehensive, Columbus, OH, USA
  9. 9Dana-Farber Cancer Center, Boston, MA, USA
  10. 10University of Bologna, Bologna, Italy
  11. 11University of Parma, Parma, Italy
  12. 12Universitaria Sant’Andrea, Rome, Italy
  13. 13Istituto Nazionale Tumori IRCCS, Napoli, Italy
  14. 14East Carolina University Brody School of, Greenville, USA
  15. 15Cleveland Clinic Foundation, Cleveland, OH, USA
  16. 16Sapienza University of Rome, Rome, Italy
  17. 17IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy
  18. 18Università degli Studi di Genova, Genova, Italy
  19. 19IRCCS Ospedale Policlinico San Martino, Genova, Italy
  20. 20Imperial College London, London, UK
  21. 21National Cancer Institute, Silver Spring, MD, USA


Background Immune 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.

Methods This 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.

Results Median 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 (<85,85–89,>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 <85, 85–89, and ≥90 years (p=0.15). Despite similar rates of G3+ irAEs, ICIs were discontinued due to irAE more than twice as often among patients ≥90 years compared to patients <90 years (30.9% vs. 15.1%, p=0.008) (table 1).

Conclusions ICIs are effective and generally well-tolerated among older patients with cancer. However, ICI discontinuation due to irAE is more frequent with increasing age.

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