Dr Haight on Predictors of Treatment Toxicity in Gynecologic Malignancies

Paulina J. Haight, MD, obstetrician/gynecologist, Ohio State College of Medicine, Ohio State University Cancer Center–James, discusses findings from an investigation into predictors of toxicity and response to treatment with lenvatinib (Lenvima) plus pembrolizumab (Keytruda) in patients with gynecologic malignancies, which were presented at the 2024 SGO Winter Meeting.

The study evaluated 88 patients, most of whom presented with endometrial cancer (88%) and a smaller proportion (11%) of whom presented with ovarian or primary peritoneal cancer, Haight begins. Predominantly, patients exhibited serous (32%), endometrioid (26%), or carcinosarcoma (17%) histology, and 87% of tumors were mismatch repair proficient, Haightadds.

Patients were categorized based on the number of toxicities they experienced: 13 had no toxicity, 27 experienced 1 to 2 toxicities, 28 had 3 to 4 toxicities, and 21 encountered 5 or more toxicities, she elucidates. Analysis of patient demographics and clinical-pathologic information revealed an association between the incidence of toxicity and the neutrophil-to-lymphocyte ratio, suggesting a higher incidence of toxicity with a lower neutrophil-to-lymphocyte ratio (less than 6), Haight adds. However, no significant associations were found with other demographic or clinicopathologic features, she details.

Looking to clinical outcomes, the overall response rate (ORR) with lenvatinib plus pembrolizumab correlated significantly with the incidence of treatment-related toxicities, indicating that patients with more toxicities were more likely to respond to treatment, Haight expands. For example, patients with no toxicity had an 11% ORR, and those with 5 or more toxicities exhibited an ORR of 62%, she explains.

A higher proportion of patients who responded to the treatment experienced intense toxicity, with 32% having grade 3 or 4 toxicity compared with 24% in patients with stable disease and 13% in those with progressive disease (P = .032), Haight continues. Notably, responders with 5 or more toxicities demonstrated a significantly longer median duration of response of 18 months compared with medians of 6, 10, and 7 months in patients with 0, 1 to 2, and 3 to 4 toxicities, respectively, she states. It's essential to highlight that patients receiving treatment for an extended period or receiving more cycles of treatment experienced a higher number of toxicities. However, the median time to toxicity in the overall population was only 21 days, indicating that toxicity is not solely a result of prolonged treatment duration, Haight concludes.