Representation and Outcomes of Older Adults in Practice-Changing Oncology Trials in the Era of Novel Therapies: A Guideline Appraisal

Authors: Ronald Chow MS1, Daniel E. Lage MD, MSc1, Grant R. Williams MD, MSPH2, Mina S. Sedrak MD, MS3, Joseph A. Greer PhD4, Jennifer S. Temel MD1, and Ryan D. Nipp MD, MPH1
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  • 1 Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts;
  • | 2 Division of Hematology and Oncology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama;
  • | 3 Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California; and
  • | 4 Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: Older adults account for 70% of cancer-related deaths, but previous studies have shown that they are underrepresented in cancer clinical trials. We sought to analyze the representation and outcomes of older adults in trials conducted in the era of novel targeted therapy and immunotherapy. Methods: We searched the 2020 NCCN Clinical Practice Guidelines in Oncology and retrieved trials from the past 10 years leading to category 1 recommendations in the first-line metastatic setting for the 5 most common causes of cancer death. We categorized trials by cancer type, single-agent versus multiagent approach, and therapeutic class. We described the percentage of older adults (according to each trial’s definition) and used a Mantel-Haenszel random-effects meta-analysis model to compare overall and progression-free survival by age. Results: We identified 30 trials consisting of 24,416 patients. Across all trials, 44% of enrolled patients were older adults. Representation of older adults by cancer type within trials was 49% prostate cancer, 38% pancreatic cancer, 37% breast cancer, and 34% non–small cell lung cancer. Representation of older adults also varied by therapeutic class: 20% received immunotherapy, 44% received cytotoxic chemotherapy, 54% received targeted/hormonal therapy, and 34% received combination therapy (P<.001 for all comparisons). For each year since 2010, the percentage of older adults enrolled in trials increased by 1.9%, although this difference was not significant. We observed no difference in overall or progression-free survival between older and younger adults. In our analysis of practice-changing clinical trials, we found that 44% of clinical trial participants were older adults. Trials that included immunotherapy or a combination of therapeutic classes had a lower representation of older adults (<40%). Conclusions: We found that >40% of patients in practice-changing trials are older adults. Although they remain underrepresented in clinical trials compared with the general population, older adults in practice-changing trials seem to be better represented than in previously reported analyses of cooperative group trials.

Submitted December 21, 2020; final revision received March 29, 2021; accepted for publication April 28, 2021.

Author contributions: Study concept and design: All authors. Acquisition, analysis, and interpretation of data: All authors. Writing – original draft: All authors. Writing – review & editing: All authors.

Disclosures: Dr. Sedrak has disclosed receiving research support from the National Institute of Aging (R03AG064377; Principal Investigator) and NCI (K12CA001727). Dr. Greer has disclosed receiving research support from Blue Note Therapeutics and receiving royalties from Springer (Humana Press). The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this article was supported by the NCI of the NIH under award number NIH T32 CA092203.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Daniel E. Lage, MD, MSc, Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Lawrence House, Boston, MA 02114. Email: dlage@mgh.harvard.edu

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