Only Certain Gynecologic Malignancies Benefit from Immunotherapy

Certain histologies may be better suited for immunotherapy treatment compared with others — all determined by microsatellite instability-high (MSI-H) status, tumor mutation burden (TMB) and PD-L1 expression.

In particular, women with specific cervical and ovarian cancers would benefit most, 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.

“Immune checkpoint inhibitor therapies have profoundly changed the treatment landscape of various cancers including non-small cell lung cancer and melanoma, and data is emerging in gynecologic malignancies,” the researchers wrote.

Patients whose tumors test positive for MSI-H status have proven to see improved responses from immune checkpoint inhibitor therapies; however, recent studies have shown that increased PD-L1 expression and elevated TMB are also associated with better outcomes.

“PD-L1 mediates tumor-induced immune suppression through T-cell downregulation, (and) MSI and TMB levels likely create neoantigens which may increase (the) likelihood of response to immunotherapy,” the researchers explained. “Looking at these three signatures may result in focusing our treatment on those tumors that (have a) higher likelihood of responding to immunotherapy.”

Therefore, the researchers retrospectively analyzed 5,588 tumors by multiplatform profiling, which included 3,223 ovarian, 1,989 uterine, 283 cervical, 49 vulvar and 19 vaginal tumors. Next generation sequencing (NGS) was then performed on 592 genes.

In total, 16 percent of uterine cancers, 1 percent of ovarian cancers, 2 percent of cervical cancers and no vulvar or vaginal cancers had MSI-H status; and 13 percent of uterine cancers, 2 percent of ovarian cancers, 6 percent of cervical cancers, 6 percent of vulvar cancers and 21 percent of vaginal cancers were TMB-high. PD-L1 expression was observed in only 7 percent of uterine and ovarian tumors but, of note, in 28 percent of cervical, 63 percent vulvar and 47 percent of vaginal cancers.

By cancer histology, MSI and TMB appeared to be highly correlated. However, there was a limited correlation between TMB and PD-L1 expression in all tumor types except for ovarian clear cell and serous tumors, as well as uterine leiomyosarcoma. Similarly, a limited correlation was also seen between MSI and PD-L1 expression in all tumors except uterine serous, ovarian mucinous and serous tumors.

Lastly, the researchers found no correlation between MSI, TMB and PD-L1 expression among tumors, except for ovarian serous and clear cell tumors.

The researchers identified triple negative phenotype in more than 85 percent of uterine serous, leiomyosarcoma and stromal sarcoma; and of ovarian serous, carcinosarcoma, leiomyosarcoma and low grade tumors.

Single or double biomarkers were seen in more than 15 percent of cervical tumors; uterine squamous, clear cell and endometrioid tumors; ovarian clear cell, endometrioid and germ cell tumors; and vulvar and vaginal tumors.

Triple positive biomarkers occurred in less than 5 percent of all cancers studied.

Therefore, the researchers concluded that the following cancers would benefit from immunotherapy most: cervical, vulvar, vaginal, uterine endometrioid and clear cell; and ovarian endometrioid, clear cell, mucinous and germ cell cancers.

“Given each cancer demonstrates a unique phenotype, panel results may be key in directing therapy,” they added.