Neoadjuvant Pembrolizumab in Localized MSI-H/dMMR Solid Tumors

Get Permission

In a single-center phase II trial reported in the Journal of Clinical Oncology, Ludford et al found that neoadjuvant pembrolizumab produced a high pathologic complete response rate and radiographic objective response rate in patients with localized microsatellite instability–high/mismatch repair–deficient (MSI-H/dMMR) solid tumors.

Study Details

In the study, 35 patients with localized unresectable or high-risk resectable MSI-H/dMMR tumors were enrolled at The University of Texas MD Anderson Cancer Center between October 2019 and March 2021, including 27 with colorectal cancer and 26 with stage III disease. Patients were to receive pembrolizumab at 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation. An option for nonsurgical management was provided in which patients could receive pembrolizumab for 16 cycles followed by observation. The primary endpoint was pathologic complete response rate among patients undergoing surgery after three or more cycles of pembrolizumab.

Key Findings

At data cutoff (end March 2022), 17 patients had undergone and 18 patients had not undergone surgical resection.

Among 15 patents evaluable for the primary endpoint, pathologic complete response was achieved in 10 (67%, 95% confidence interval [CI] = 38%–88%). Among all 17 patients who underwent surgery, pathologic complete response was achieved in 11 (65%). Of 14 patients with colorectal cancer who underwent surgery, pathologic complete response was achieved in 11 (79%).

Among 33 patients evaluable for radiographic response, objective response was observed in 27 (82%), with complete response in 10 (30%); an additional 6 patients (18%) had stable disease.

Of 30 patients with luminal gastrointestinal cancers, 19 were evaluable for endoscopic response; of these, complete response was observed in 12 (63%), with the remainder having incomplete response. Among patients with complete endoscopic response, five underwent resection, with all having pathologic complete response. Of the seven patients with incomplete response, three underwent resection, with pathologic complete response observed in two.

Among the 18 patients who did not undergo surgical resection, median follow-up from last dose of pembrolizumab was 38 weeks (range = 0–103 weeks). A total of 10 patients chose to receive 1 year of pembrolizumab followed by surveillance without surgical resection; none of these patients experienced disease progression. An additional eight did not undergo surgical resection and received less than 1 year of pembrolizumab; five selected an organ-sparing approach, with radiographic complete responses in three and stable disease in two. Disease progression occurred in one patient with stable disease.

During the study and subsequent follow-up, disease progression occurred in six patients, of whom four underwent salvage surgery. Spatial immune profiling with imaging mass cytometry showed significantly closer proximity between granulocytic cells and cytotoxic T cells in patients with disease progression vs those without disease progression.

Grade 1 or 2 treatment-related adverse events occurred in 13 patients (37%); treatment-related grade 3 adverse events (no grade 4 events) were observed in 2 patients (6%).

The investigators concluded, “Neoadjuvant pembrolizumab in dMMR/MSI-H cancers is safe and resulted in high rates of pathologic, radiographic, and endoscopic response, which has implications for organ-sparing strategies.”

Kaysia Ludford, MD, of the Department of General Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Cancer Institute, Kavanagh Family Foundation, and Merck. For full disclosures of the study authors, visit


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.