Author:
Kang Yoon-Jung,O’Haire Sophie,Franchini Fanny,IJzerman Maarten,Zalcberg John,Macrae Finlay,Canfell Karen,Steinberg Julia
Abstract
AbstractImmune checkpoint inhibitors have been approved in the USA for tumours exhibiting mismatch repair deficiency (dMMR), microsatellite instability (MSI), or high tumour mutational burden (TMB), with regulatory and reimbursement applications in multiple other countries underway. As the estimated budget impacts of future reimbursements depend on the size of the potential target population, we performed a scoping review and meta-analysis of the prevalence of these pan-tumour biomarkers in different cancers. We systematically searched Medline/Embase and included studies reporting the prevalence of dMMR/MSI/high TMB in solid tumours published 01/01/2018–31/01/2021. Meta-analyses were performed separately for the pan-cancer prevalence of each biomarker, and by cancer type and stage where possible. The searches identified 3890 papers, with 433 prevalence estimates for 32 different cancer types from 201 studies included in meta-analyses. The pooled overall prevalence of dMMR, MSI and high TMB (≥ 10 mutations/Mb) in pan-cancer studies was 2.9%, 2.7% and 14.0%, respectively. The prevalence profiles of dMMR/MSI and high TMB differed across cancer types. For example, endometrial, colorectal, small bowel and gastric cancers showed high prevalence of both dMMR and MSI (range: 8.7–26.8% and 8.5–21.9%, respectively) and high TMB (range: 8.5–43.0%), while cervical, esophageal, bladder/urothelial, lung and skin cancers showed low prevalence of dMMR and MSI (< 5%), but high prevalence of high TMB (range: 23.7–52.6%). For other cancer types, prevalence of all three biomarkers was generally low (< 5%). This structured review of dMMR/MSI/high TMB prevalence across cancers and for specific cancer types and stages provide timely evidence to inform budget impact forecasts in health technology assessments for drug approvals based on these pan-tumour biomarkers.
Funder
Medical Research Future Fund
PRIMCAT
Publisher
Springer Science and Business Media LLC
Reference40 articles.
1. Pestana, R. C., Sen, S., Hobbs, B. P. & Hong, D. S. Histology-agnostic drug development—Considering issues beyond the tissue. Nat. Rev. Clin. Oncol. 17(9), 555–568 (2020).
2. Lemery, S., Keegan, P. & Pazdur, R. First FDA approval agnostic of cancer site—When a biomarker defines the indication. N. Engl. J. Med. 377(15), 1409–1412 (2017).
3. U.S. Food & Drug Administration. FDA News release: FDA approves first cancer treatment for any solid tumor with a specific genetic feature. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cancer-treatment-any-solid-tumor-specific-genetic-feature. Accessed 21 October 2020.
4. Therapeutic Goods Administration. Prescription medicines: new or extended uses, or new combinations of registered medicines, 2019. https://www.tga.gov.au/prescription-medicines-new-or-extended-uses-or-new-combinations-registered-medicines-2019. Accessed 21 October 2020.
5. Merck Receives Positive EU CHMP Opinion for KEYTRUDA® (pembrolizumab) as First-Line Treatment in Adult Patients With Metastatic Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Colorectal Cancer. https://www.merck.com/news/merck-receives-positive-eu-chmp-opinion-for-keytruda-pembrolizumab-as-first-line-treatment-in-adult-patients-with-metastatic-microsatellite-instability-high-msi-h-or-mismatch-repair-deficien/. Accessed 23 December 2021.
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