Immune checkpoint inhibitor therapies (ITs) have profoundly changed the treatment landscape of various cancers including NSCLC and melanoma, and data is emerging in gynecologic malignancies 1. While MSI‐H status qualifies patients for IT regardless of tumor type2, increased expression of PD‐L1 and elevated tumor mutational burden have been associated with higher likelihood of responding3. PD‐L1 mediates tumor‐induced immune suppression through T‐cell downregulation, MSI and TMB levels likely create neoantigens which may increase likelihood of response to IO. Looking at these three signatures may result in focusing our treatment on those tumors that higher likelihood of responding to IO.
- 5588 tumors were retrospectively analyzed by multiplatform profiling: 3223 ovarian, 1989 uterine, 284 cervical, 49 vulvar and 19 vaginal
- NextGen sequencing (NGS) was performed on 592 genes (Illumina NextSeq platform).
- Mutational burden calculated based on somatic nonsynonymous missense mutations; TMB‐high was defined as ≥17 mutations/megabase.
- Microsatellite Instability (MSI) was determined by examining altered microsatellite loci using NGS ( ≥46 loci).
- Antibody used for PD‐L1 was SP142 and positivity was defined as ≥2+, >5% staining on tumor cells.
- Data were compared using chi‐square tests.
- MSI and TMB were highly correlated (p<0.0006)
- Limited correlation between TMB/PD‐L1 (except in ovarian clear cell and serous and uterine leiomyosarcoma) and MSI/PD‐L1 (except in uterine serous, ovarian mucinous and serous).
- No significant correlation for MSI/TMB/PD‐L1 except in ovarian serous and Clear cell (p<0.05).
- >85% tumors uterine serous, carcinosarcoma, leiomyosarcoma and stromal sarcomas as well as ovarian serous, carcinosa
- Given this, certain histologies appear better suited for immunotherapy: cervical, vulvar, vaginal, uterine endometriod and clear cell, and ovarian endometriod, clear cell, mucinous, germ cell cancers.
- Given each cancer demonstrates a unique phenotype, panel results may be key in directing therapy.