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Nivolumab for Mismatch Repair–Deficient Noncolorectal Cancers


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In a study (NCI-MATCH trial subprotocol, arm Z1D) reported in the Journal of Clinical Oncology, Azad et al found that nivolumab was active in mismatch repair–deficient noncolorectal cancers.

As stated by the investigators, “The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial, the largest national precision oncology study to date (more than 1,100 sites) of patients with relapsed or refractory malignancies, assigned patients to targeted therapy in parallel phase II studies based on tumor molecular alterations. The anti–programmed [cell] death receptor 1 inhibitor nivolumab previously showed activity in … MMR-deficient colon cancer. We hypothesized that nivolumab would have activity in patients with MMR-deficient, noncolorectal tumors.”

Study Details

In the study, eligible patients with relapsed or refractory tumors were screened for molecular alterations. MMR deficiency was defined as complete loss of nuclear expression of MLH1 or MSH2 MMR gene products by immunohistochemistry. Patients with MMR-deficient colorectal cancer were excluded. Patients with MMR-deficient disease received nivolumab at 3 mg/kg every 2 weeks in 28-day cycles and at 480 mg every 4 weeks after cycle 4.

Of 4,902 screened patients, 2% had MMR-deficient cancer. A total of 42 evaluable patients with noncolorectal cancers were enrolled. Patients had a median age of 60 years and a median of three prior therapies. The most common disease types seen in patients were endometrioid endometrial adenocarcinoma (n = 13), prostate adenocarcinoma (n = 5), and uterine carcinosarcoma (n = 4).

Key Findings

KEY POINTS

  • Objective response on RECIST version 1.1 criteria was observed in 15 patients (36%), with complete response in 3 (7%).
  • Median progression-free survival was 6.3 months, with estimated 12- and 18-month rates of 46.2% and 31.4%. Median overall survival was 17.3 months.

Objective response on Response Evaluation Criteria in Solid Tumors, version 1.1, was observed in 15 patients (36%), with complete response in 3 (7%). An additional nine patients (21%) had stable disease. Patients with response included those with endometrioid endometrial, esophageal, breast, and prostate cancers, as well as other cancer types.

Median progression-free survival was 6.3 months, with estimated 12- and 18-month rates of 46.2% and 31.4%. Median overall survival was 17.3 months.

The most common grade 1 to 3 treatment-related adverse events were fatigue (in 40% of patients), anemia (33%), rash (17%), and hypoalbuminemia (17%). The most common grade 3 adverse event reported was anemia (7%). Grade 4 adverse events occurred in three patients (sepsis in two and pneumonitis in one).

The investigators concluded, “A variety of refractory cancers (2.0% of those screened) had MMR deficiency as defined in NCI-MATCH. Nivolumab has promising activity in MMR-deficient noncolorectal cancers of a wide variety of histopathologic types.”

Nilofer S. Azad, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Cancer Institute grants. For full disclosures of the study authors, visit ascopubs.org.

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®.
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