Pembrolizumab/Lenvatinib Yields Durable Responses in Platinum-Sensitive Recurrent Ovarian Cancer

Pembrolizumab/Lenvatinib in Ovarian Cancer

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The combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) produced durable responses in patients with platinum-sensitive recurrent ovarian cancer, according to data from an investigator-initiated phase 2 trial (NCT04519151) presented at the 2024 ASCO Annual Meeting.

Findings showed that patients treated with the combination (n = 24) achieved an overall response rate (ORR) of 54%, which included a complete response rate of 13% and a partial response rate of 42%. Twenty-nine percent of patients experienced stable disease, and 13% had progressive disease. One patient was not assessed for response after withdrawing from the study early due to toxicity. The median duration of response was 8 months (95% CI, 7-not reached [NR]), and 31% of responses persisted for more than 18 months.

“Biomarker analysis, including tumor RNA sequencing, immune phenotyping, and fecal and vaginal microbiome composition, is currently in progress to define patients with likelihood of benefit,” lead study author Smadar Bauer, MD, of Sheba Medical Center in Ramat Gan, Israel, and colleagues, wrote in a poster presentation of the data.

The single-site, single-arm study enrolled patients with platinum-sensitive recurrent ovarian cancer of high-grade serous or endometroid histology. Patients were required to have an ECOG performance status of 0 or 1, adequate organ function, and measurable disease per RECIST 1.1 criteria. Up to 2 prior lines of chemotherapy were permitted. Previous maintenance therapy consisting of bevacizumab (Avastin) or PARP inhibitors was allowed. Patients could also have received prior hormonal treatment for active disease or as maintenance.

All patients received 200 mg of intravenous pembrolizumab once every 3 weeks for up to 35 cycles in combination with 20 mg of oral lenvatinib once per day.

Investigator-assessed ORR served as the trial’s primary end point. Secondary end points consisted of progression-free survival (PFS), overall survival (OS), quality of life, and safety and tolerability. Biomarkers to correlate the potential for clinical benefit were an exploratory end point.

Among the 24 patients enrolled between May 2021 and July 2023, the median age was 60 years (range, 45-78), and half of patients were below the age of 65. At enrollment, 46% of patients had stage IIIC disease, and 54% had stage IV disease. High-grade serous histology was reported in 79.2% of patients, and the remaining 20.8% had adenocarcinoma. Patients either had an ECOG performance status of 0 (75%) or 1 (25%).

Forty-six percent of patients received neoadjuvant chemotherapy as first-line therapy. The last dose of platinum-based chemotherapy was administered 6 to 12 months prior to enrollment in 42% of patients, and the remaining 58% of patients were more than 12 months removed from their last platinum treatment. Moreover, 37.5% of patients received 1 prior line of therapy, and 62.5% were given 2 prior lines. Half of patients received prior bevacizumab, and 46% received a prior PARP inhibitor.

Twenty-one percent of patients harbored BRCA mutations. Moreover, 4% of patients were positive for non-BRCA homologous recombination–deficient (HRD) mutations, and HRD status was unknown in 29% of patients. Seventy-one percent of patients had a CA-125 level up to 10 times the upper limit of normal (ULN), and 29% had levels above 10 times the ULN.

Additional data demonstrated that the median PFS was 5.5 months (95% CI, 4-8), and the median OS was 30 months (95% CI, 17-NR). “OS is comparable with standard-of-care practice for platinum-sensitive recurrence,” the study authors wrote.

Regarding safety, grade 1/2 adverse effects (AEs) occurred in 96% of patients, and the rate of grade 3/4 AEs was 67%. Seventy-nine percent of patients experienced any AE leading to dose reduction. Nephrotic range proteinuria, hepatitis, and diabetic ketoacidosis were AEs that led to treatment discontinuation in 1 patient each.

The most common treatment-related AEs included abdominal pain, arthralgia, asthenia, diarrhea, fatigue, hair loss, hand-foot syndrome, headache, hepatitis, hoarseness, hypertension, hyperthyroidism, hypothyroidism, mucositis, myalgia, rash, and weakness.

“AEs were manageable, with hypertension being the most prevalent grade 3/4 toxicity,” the study authors wrote. “AEs, except for endocrinopathies, were reversible upon treatment withdrawal.”

Reference

Bauer S, Saad A, Greenhouse I, et al. Phase II study of pembrolizumab and lenvatinib in platinum sensitive recurrent ovarian cancer. J Clin Oncol. 2024;42(suppl 16):5581. doi:10.1200/JCO.2024.42.16_suppl.5581