FDA approves companion diagnostic for pembrolizumab in MSI-H solid tumors


The FDA has approved FoundationOneCDx for use as a companion diagnostic to identify patients with solid tumors that are microsatellite instability high (MSI-H) and thus eligible to be treated with the immunotherapy pembrolizumab (Keytruda).1

Pembrolizumab was approved by the FDA in 2017 for the treatment of patients with MSI-H or mismatch repair deficient solid tumors.2 The emergence of such tumor-agnostic approvals has increased the significance of genomic profiling in urology, as patients with prostate, bladder, or kidney cancer may benefit from these therapies.

“Immunotherapy has huge promise as a potential treatment option for patients with advanced cancer; however, identifying those who may benefit is complex and requires high-quality diagnostics,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, the developer of FoundationOneCDx stated in a news release. “Not only could this approval allow more patients to benefit from Keytruda, but it also underscores an important shift toward tumor-agnostic cancer care.”

Approval of pembrolizumab for MSI-H

The 2017 approval of pembrolizumab for patients with MSI-H/dMMR solid tumors was based on data from 149 patients with MSI-H or dMMR cancers enrolled across 5 single-arm clinical trials. Ninety patients had colorectal cancer (CRC) and the remaining 59 patients had 1 of 14 other tumor types.

The objective response rate (ORR) with pembrolizumab was 39.6% (95% CI, 31.7-47.9), including 11 (7.4%) complete responses (CRs) and 48 (32.2%) partial responses (PRs). The ORR was 36% in patients with CRC and 46% in patients with other tumor types. The median duration of response was not yet reached (range, 1.6+ months to 22.7+ months). Among patients who responded to pembrolizumab, 78% had responses that lasted for at least 6 months.

The pivotal data for the approval included patients from the KEYNOTE-016 (n = 58), KEYNOTE-164 (n = 61), KEYNOTE-012 (n = 6), KEYNOTE-028 (n = 5), and KEYNOTE-158 (n = 19) trials. Pembrolizumab was administered at 200 mg every 3 weeks or 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or a maximum of 24 months.

The median age among the 149 patients was 55 years, with 36% of patients aged 65 or older. Across the population, 77% of patients were white, 56% were male, 36% had an ECOG performance status (PS) of 0, and 64% had an ECOG PS of 1.

Two percent of patients had locally advanced, unresectable disease, and 98% of patients had metastatic disease. Among patients with metastatic or unresectable disease, the median number of prior therapies was 2. In patients with metastatic CRC, 84% had received at least 2 prior lines of therapy, compared with 53% in patients with other solid tumors.

Beyond CRC, other tumor types in which patients had responses included endometrial cancer (n = 5), biliary cancer (n = 3), gastric or GE junction cancer (n = 5), pancreatic cancer (n = 5), small intestinal cancer (n = 3), breast cancer (n = 2), prostate cancer (n = 1), esophageal cancer (n = 1), retroperitoneal adenocarcinoma (n = 1), and small cell lung cancer (n = 1).

In its news release on the approval, the FDA listed common side effects of pembrolizumab, including fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and nausea. Immune-mediated side effects associated with pembrolizumab include pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.


1. U.S. FDA Approves FoundationOne®CDx as a Companion Diagnostic for KEYTRUDA® (pembrolizumab) to Identify Patients with Microsatellite Instability-High (MSI-H) Solid Tumors. Published online February 22, 2022. Accessed February 22, 2022. https://bwnews.pr/3sc9ooL

2. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. Published online May 23, 2017. Accessed February 22, 2022. https://bit.ly/3p8hVqH

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