High-Grade Endometrioid Endometrial Cancers Likely to Benefit from Immunotherapy

Patients with high-grade endometrioid endometrial cancer may benefit from immunotherapy treatment compared with women with lower-grade disease, according to study results presented during the 49th Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancers held in New Orleans March 24-27.

Endometrioid endometrial cancer is categorized on a histologic continuum from grade 1 to 3 — including grade 1 (low grade), grade 2 (moderate grade) and grade 3 (high grade). As the malignancy increases in grade, as does its aggressive behavior, resulting in a poor prognosis for these women.

Unfortunately, treatment options for advanced or recurrent endometrioid endometrial cancer are limited. However, emerging data on immune checkpoint therapy in gynecologic malignancies has shown promise; and microsatellite instability-high (MSI-H) status, tumor mutation burden and high PD-L1 expression have been associated with higher response rates to this therapy.

Therefore, the researchers — from Mitchell Cancer Institute, University of South Alabama,

Caris Life Sciences, UC Health Barrett Cancer Center and Wayne State University — aimed to identify distinct immune “biomarker phenotypes” to identify women with endometrioid endometrial cancer who may benefit from immune therapy.

In the retrospective study, the researchers analyzed 621 tumors for immune biomarker phenotype by multiplatform profiling — including 156 grade 3 tumors, 172 grade 2, 113 grade 1 and 180 unknown. Next generation sequencing (NGS) was performed on 592 genes, while tumor mutational load was calculated as having 17 or more gene mutations.

Overall, MSI-H status was found among 203 tumors (33 percent). High-grade tumors appeared to have the most frequent MSI-H status (58 tumors; 37 percent), followed by progressive decline in grade 2 (55 tumors; 32 percent) and grade 1 tumors (25 tumors; 22 percent) that was statistically significant.

Tumor mutation load-high status was found in 152 tumors (25 percent). Similar to MSI-H status, tumor mutation load-high status appeared most common in high-grade tumors (53 tumors; 34 percent), with a statistically significantly decline noted as tumor grade decreased to grade 2 (39 tumors; 23 percent) and grade 1 (15 tumors 13 percent).

PD-L1 expression was found in 33 tumors (5.5 percent). Consistent with MSI-H and tumor mutational load-high status, high-grade tumors showed the most frequent PD-L1 expression (18 tumors; 12 percent), with a statistically significant decrease in expression frequency as tumor grade decreased to grade 2 (five tumors; 3 percent) and grade 1 (one tumor; 0.9 percent).

“MSI and tumor mutation burden are highly correlated in low grade, intermediate and high-grade tumors, while the correlation of PD-L1 expression with MSI or tumor mutation burden is not seen,” the researchers wrote.

In addition, the researchers evaluated triple negative biomarker phenotype as a potential surrogate marker of low tumor immunogenicity. The tripe negative phenotype was identified in 77 grade 1 tumors (72 percent) compared with 101 grade 2 tumors (60 percent) and 80 grade 3 tumors (52 percent).

The researchers noted this finding suggests, “a higher incidence of immunogenic drivers with increasing tumor grade.”

“High-grade tumors appear to be more immunogenic than low-grade tumors and may preferentially benefit from immunotherapy treatment providing a potentially powerful treatment option,” they concluded. “Conversely, low-grade tumors are less likely to benefit from immunotherapy treatment and other treatment options should be considered.”