Real-World Treatment Patterns and Clinical Outcomes for Standard of Care Regimens in Patients with Deficient MMR or MSI-High Metastatic Colorectal and Non-Colorectal Cancer: A Retrospective Chart Review Study in France

Adv Ther. 2022 Mar;39(3):1215-1229. doi: 10.1007/s12325-021-01956-8. Epub 2022 Jan 13.

Abstract

Introduction: There is limited evidence on the effectiveness of standard of care (SOC) treatments in previously treated patients with deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H) metastatic cancer. Immune checkpoints inhibitors (ICIs) have emerged as key treatments for dMMR/MSI-H tumors. However, clinical outcomes data with SOC regimens are still limited. Study objectives were to evaluate real-world treatment patterns and clinical outcomes in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) and non-CRC receiving SOC regimens. Given the resulting small cohort of patients with metastatic non-CRC, only summary results are provided.

Methods: Two French university hospitals participated in a retrospective chart review study in which adult patients with dMMR/MSI-H mCRC and non-CRC were enrolled. Treatment patterns, overall survival (OS) from the start of third-line (3L, for mCRC) or second-line (2L, for non-CRC) treatment, and the best overall response rate (BORR) were reported.

Results: Thirty-six patients with dMMR/MSI-H mCRC were included. Almost all patients received combination treatments both in first-line (1L, 100%) and 2L (97%). For 3L and later, combination treatment was preferred over monotherapy but decreased in usage (75% at 3L and 57% at fourth-line, 4L). The BORR was 5.7% and median OS for patients with dMMR/MSI-H mCRC receiving 3L therapy was 9.0 months (95% confidence interval, CI 4.0-14.1); it decreased to 4.1 months (95% CI 4.0-9.0) when survival data of patients receiving ICIs at fourth or later lines were censored at progression date of prior treatment line.

Conclusion: Real-world clinical outcomes observed for patients with dMMR/MSI-H mCRC receiving 3L treatment(s) are suboptimal, suggesting a high unmet need that could be addressed with ICIs.

Keywords: Chemotherapy treatments; Deficient mismatch repair/microsatellite instability high; Immune checkpoints inhibitors; Metastatic colorectal cancer; Overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • DNA Mismatch Repair
  • Humans
  • Microsatellite Instability*
  • Retrospective Studies
  • Standard of Care